Miracle-dz/UniFAR-FTUs huggingface dataset:
EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice

Background: EphrinA1-Fc abolishes acute I/R injury and attenuates nonreperfused cardiac injury 4 days after permanent occlusion in mice. The goal of this study was to assess the capacity of a single intramyocardial administration of ephrinA1-Fc at the time of coronary artery ligation, to determine the degree to which early salvage effects translate to reduced adverse remodeling after 4 weeks of nonreperfused myocardial infarction (MI) in wild-type B6 and EphA2-R-M (EphA2 receptor null) mice. Methods: At 4 weeks post-MI, echocardiography, histologic and immunohistochemical analyses of B6 mouse hearts were performed. Primary mouse cardiac fibroblasts (FBs) isolated from B6 mice cultured in the presence of low and high dose ephrinA1-Fc, both with and without pro-fibrotic TGF-β stimulation and Western blots, were probed for relative expression of remodeling proteins MMP-2, MMP-9 and TIMP-1, in addition to DDR2 and (p)SMAD2/3/totalSMAD2/3. Results: EphrinA1-Fc preserved a significant degree of contractile function, decreased adverse left ventricular remodeling, attenuated excessive compensatory hypertrophy, and decreased interstitial fibrosis in wild-type (WT) B6 mouse hearts. In contrast, most of these parameters were poorer in ephrinA1-Fc-treated EphA2-R-M mice. Of note, fibrosis was proportionately decreased, implying that other EphA receptor(s) are more important in regulating the pro-fibrotic response. Primary FBs showed disparate alteration of MMP-2, MMP-9 and TIMP-1, as well as DDR2 and p-SMAD2/3/totalSMAD2/3, which indicates that matrix remodeling and cardiac fibrosis in the injured heart are influenced by ephrinA1-Fc. Conclusion: This study demonstrates the capacity of a single administration of ephrinA1-Fc at the onset of injury to attenuate long-term nonreperfused post-MI ventricular remodeling that results in progressive heart failure, and the important role of EphA2 in mitigating the deleterious effects.
Oxidative Stress Markers and the Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.
Identification of a Novel Gene, Osbht, in Response to High Temperature Tolerance at Booting Stage in Rice

Rice is one of the world’s leading food crops, and over 90% of the world’s rice production stems from Asia. In particular, an increase of 1 °C in the minimum temperature reduces the quantity of rice by 10%. Therefore, the development of rice varieties that can stably maintain the yield and quality of the rice even under these rapid climate changes is indispensable. In this study, we performed quantitative trait loci (QTL) mapping after treatment with heat stress during the booting stage in rice. We performed a QTL analysis using the Cheongcheong/Nagdong double haploid (CNDH) line and identified 19 QTLs during the 2 year analysis. Of these QTL regions, the 2.2 cM region of RM3709–RM11694 on chromosome 1 was shared among the six traits (heading date; culm length; panicle length; number of tiller; 1000 grain weight; and content of chlorophyll) examined. Rice Microsatellite (RM) 3709–RM11694 contained 27 high-temperature-tolerance candidate genes. Among the candidate genes, OsBHT showed a different gene expression level between CNDH75, which is a high-temperature tolerant line, and CNDH11 which is a susceptible line. Although some existing high-temperature-tolerant genes have been reported, OsBHT can be used more effectively for the development of heat tolerance in rice.
Assessing the Pyloric Caeca and Distal Gut Microbiota Correlation with Flesh Color in Atlantic Salmon (Salmo salar L., 1758)

The Atlantic salmon (Salmo salar L., 1758) is a temperate fish species native to the northern Atlantic Ocean. The distinctive pink–red flesh color (i.e., pigmentation) significantly affects the market price. Flesh paleness leads to customer dissatisfaction, a loss of competitiveness, a drop in product value and, consequently, severe economic losses. This work extends our knowledge on salmonid carotenoid dynamics to include the interaction between the gut microbiota and flesh color. A significant association between the flesh color and abundance of specific bacterial communities in the gut microbiota suggests that color may be affected either by seeding resilient beneficial bacteria or by inhibiting the negative effect of pathogenic bacteria. We sampled 96 fish, which covered all phenotypes of flesh color, including the average color and the evenness of color of different areas of the fillet, at both the distal intestine and the pyloric caeca of each individual, followed by 16S rRNA sequencing at the V3-V4 region. The microbiota profiles of these two gut regions were significantly different; however, there was a consistency in the microbiota, which correlated with the flesh color. Moreover, the pyloric caeca microbiota also showed high correlation with the evenness of the flesh color (beta diversity index, PERMANOVA, p = 0.002). The results from the pyloric caeca indicate that Carnobacterium, a group belonging to the lactic acid bacteria, is strongly related to the flesh color and the evenness of the color between the flesh areas.
Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas

The presenting symptoms of the tumor suppressor gene syndrome neurofibromatosis type 2 (NF2) are often non-specific and unrelated to the disease hallmark bilateral vestibular schwannomas (VS). However, age at onset and presenting symptoms may have predictive values for the clinical course of VS. In this retrospective single-center study, we addressed this issue by reviewing 106 patients with 194 VS. Presenting symptoms attributable to VS commonly occur in 87% of adults and 31% of children. Age at onset significantly correlates with tumor volumes at presentation (p = 0.034). In addition, age at onset significantly correlates with pure-tone average (p = 0.0001), speech discrimination scores (p = 0.001), age at beginning of hearing loss (p = 0.0001), age at deafness (p = 0.0001), and age at first surgery (p = 0.0001). Patients presenting with VS related symptoms had significantly (p < 0.05) worse hearing values at presentation and after surgery. These patients also exhibited higher growth rates and tumor volumes compared to patients with non-VS related presenting symptoms, but this difference did not reach the significance level of p < 0.05. Due to the late appearance of these symptoms, the time of beginning hearing loss, surgery and deafness is significantly delayed (p < 0.05) compared to patients not presenting with VS. In summary, age at onset and type of presenting symptom provide excellent prognostic parameters for predicting VS- and hearing-related clinical course.
Enteric Viral Co-Infections: Pathogenesis and Perspective

Enteric viral co-infections, infections involving more than one virus, have been reported for a diverse group of etiological agents, including rotavirus, norovirus, astrovirus, adenovirus, and enteroviruses. These pathogens are causative agents for acute gastroenteritis and diarrheal disease in immunocompetent and immunocompromised individuals of all ages globally. Despite virus–virus co-infection events in the intestine being increasingly detected, little is known about their impact on disease outcomes or human health. Here, we review what is currently known about the clinical prevalence of virus–virus co-infections and how co-infections may influence vaccine responses. While experimental investigations into enteric virus co-infections have been limited, we highlight in vivo and in vitro models with exciting potential to investigate viral co-infections. Many features of virus–virus co-infection mechanisms in the intestine remain unclear, and further research will be critical.
H∞ State Estimation for Neural Networks With General Activation Function and Mixed Time-Varying Delays

This article deals with <inline-formula> <tex-math notation="LaTeX">${H_{\infty }}$ </tex-math></inline-formula> state estimation of neural networks with mixed delays. In order to make full use of delay information, novel delay-product Lyapunov–Krasovskii functional (LKF) by using parameterized delay interval is first constructed. Then, generalized free-weighting-matrix integral inequality is used to estimate the derivative of LKF to reduce the conservatism. Also, a more general activation function is further applied by combining with parameterized delay interval in order to obtain a more accurate estimator model. Finally, sufficient conditions are derived to confirm that the estimation error system is asymptotically stable with a prescribed <inline-formula> <tex-math notation="LaTeX">${H_{\infty }}$ </tex-math></inline-formula> performance. Numerical examples are simulated to show the benefits of our proposed method.
Association between Childhood Maltreatment and Suicidal Ideation and Suicide Attempts among Chinese Adolescents: The Moderating Role of Depressive Symptoms

Suicidal behavior is a major public health concern worldwide and has become the second-leading cause of death among adolescents. The purposes of this study were to investigate the associations between childhood maltreatment and suicidal behavior and to test whether depressive symptoms have moderating effects on these associations. A multistage stratified cluster randomized sampling method was adopted to collect data from 21,019 high school students in Guangdong Province, China. The prevalence of suicidal ideation and suicide attempts among Chinese adolescents were 18.2% and 3.6%, respectively. Physical abuse (adjusted odds ratios (AOR) = 1.35, 95% confidence intervals (CI) = 1.32–1.38), emotional abuse (AOR = 1.26, 95% CI = 1.25–1.28), sexual abuse (AOR = 1.25, 95% CI = 1.21–1.30), physical neglect (AOR = 1.09, 95% CI = 1.08–1.11), and emotional neglect (AOR = 1.08, 95% CI = 1.08–1.09) were all associated with an increased risk of suicidal ideation, and these associations were also found for suicide attempts. According to stratification analyses, physical abuse/emotional abuse/sexual abuse had a stronger effect on suicidal ideation and suicide attempts among students without depressive symptoms than among students with depressive symptoms. Childhood maltreatment was associated with an increased risk of suicidal ideation and suicide attempts in Chinese adolescents. Depressive symptoms play a moderating role in the association between childhood maltreatment and suicidal behaviors.
A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.
Relationships between social status, otolith size at first feeding and subsequent growth in Atlantic salmon (Salmo salar)

Sibling Atlantic salmon fry show variation in early growth rates, despite being of a similar size initially and being in the same environment with excess food. This variation in early growth has a critical impact on their subsequent life-history strategies. We examined the relationships between social status, otolith size at first feeding and early growth rates. Fish were assessed for social status soon after first feeding, and their growth measured over the first 3 months
Abscission of mango fruitlets as influenced by biosynthesis of polyamines

Summary The role of polyamines in fruitlet abscission of mango (Magnifiera indica L.) was studied by estimating the endogenous polyamines in intact and about-to-abscind fruitlets and their pedicels, and the effect of exogenous applications of polyamines and inhibitors of polyamine biosynthesis. Endogenous free polyamines (putrescine, spermidine and spermine) were estimated in intact and about-to-abscind fruitlets and their pedicels at three developmental stages in ‘Kensington Pride’ and ‘Glen’ mango. Intact fruitlets and their pedicels exhibited 276% and 341% higher total free polyamines than about-to-abscind ones in ‘Kensington Pride’, whilst in ‘Glen’; the increase was 137% and 63%, respectively. Mean spermine concentrations were higher in intact tissues of ‘Kensington Pride’ (fruitlets 220 nmol g–1 FW, pedicels 172 nmol g–1 FW), while spermidine concentrations were greater in ‘Glen’ (fruitlets 244.5 nmol g–1 FW, pedicels 256 nmol g–1 FW). The role of spermine seems to be critical in mango fruitlet abscission as the about-to-abscind fruitlets had very low levels of spermine (10.4% and 19% of intact fruitlets) in ‘Kensington Pride’ and ‘Glen’, respectively. Exogenous applications of polyamines reduced fruitlet abscission during the initial heavy fruitlet abscission period (two weeks after fruit set) and the response was significantly influenced by type, concentration and time of application. Spermidine (0.1 mM) was the most effective of the three polyamines applied at the fruit-set stage, reducing fruitlet abscission by 6.8% compared with the control. Of the four times of application, spermine (0.1 mM) sprayed when the panicle had grown 5–8 cm showed least fruitlets abscission (91.5%) compared with controls (95.5%) after six weeks of fruit set. Higher levels of endogenous polyamines in intact fruitlets and their pedicels, compared with about-to-abscind ones, and the reduction of fruitlet abscission with exogenous application of polyamines, as well as the acceleration with inhibitors of polyamines, demonstrate the key role of polyamines biosynthesis in mango fruitlet abscission.
Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients

The detection of somatic driver mutations by next-generation sequencing (NGS) is becoming increasingly important in the care of advanced melanoma patients. In our study, we evaluated the NGS results of 82 melanoma patients from clinical routine in 2017. Besides determining the tumor mutational burden (TMB) and annotation of all genetic driver alterations, we investigated their potential as a predictor for resistance to immune checkpoint inhibitors (ICI) and as a distinguishing feature between melanoma subtypes. Melanomas of unknown primary had a similar mutation pattern and TMB to cutaneous melanoma, which hints at its cutaneous origin. Besides the typical hotspot mutation in BRAF and NRAS, we frequently observed CDKN2A deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting PDGFRA, KIT, CDK4, RICTOR, CCND2 and CHEK2. Uveal melanoma often had somatic SNVs in GNA11/Q and amplification of MYC in all cases. A significantly higher incidence of BRAF V600 mutations and EGFR amplifications, PTEN and TP53 deletions was found in patients with disease progression while on ICI. Thus, NGS might help to characterize melanoma subtypes more precisely and to identify possible resistance mechanisms to ICI therapy. Nevertheless, NGS based studies, including larger cohorts, are needed to support potential genetic ICI resistance mechanisms.
CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition

Monoacylglycerol lipase inhibition (MAGL) has emerged as an interesting therapeutic target for neurodegenerative disease treatment due to its ability to modulate the endocannabinoid system and to prevent the production of proinflammatory mediators. To obtain a beneficial response, it is necessary to understand how this inhibition affects the neuron–glia crosstalk and neuron viability. In this study, the effect of MAGL inhibition by KML29 was evaluated in two types of rat cortical primary cultures; mixed cultures, including neuron and glial cells, and neuron-enriched cultures. The risk of neuronal death was estimated by longitudinal survival analysis. The spontaneous neuronal risk of death in culture was higher in the absence of glial cells, a process that was enhanced by KML29 addition. In contrast, neuronal survival was not compromised by MAGL inhibition in the presence of glial cells. Blockade of cannabinoid type 2 (CB2) receptors expressed mainly by microglial cells did not affect the spontaneous neuronal death risk but decreased neuronal survival when KML29 was added. Modulation of cannabinoid type 1 (CB1) receptors did not affect neuronal survival. Our results show that neuron–glia interactions are essential for neuronal survival. CB2 receptors play a key role in these protective interactions when neurons are exposed to toxic conditions.
Disorders of sex development: new genetic factors and impact of medical genomics

Patients and methods Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical and covers a wide spectrum of human urogenital anomalies including gonadal dysgenesis, ambiguous genitalia, or testis development in an XX individual. Results Although there have been major advances in our understanding of the genetic pathway of human gonadal development, progress in the identification of the underlying genetic basis of DSD has been slow. It has been estimated that a molecular diagnosis is made in only around 20% of DSD, except in cases where the biochemical profile indicates a specific steroidogenic block. Conclusions This review examines recent advances in identifying genetic cause of DSD with an emphasis on the NR5A1 and GATA4 genes. We also discuss new sequencing approaches and their likely impact on the genetic analyses of DSD.
European Markets for Cultured Meat: A Comparison of Germany and France

The negative impacts of meat consumption for animals, the environment, and human health are more pressing than ever. Although some evidence points to an ongoing reduction in meat consumption in Europe, consumers are overall unwilling to cut their meat consumption in a substantial way. The present study investigates dietary identities and perceptions of cultured meat in nationally representative samples from Germany (n = 1000) and France (n = 1000). Participants were recruited through an Ipsos panel to answer an online survey, which included questions about their current and intended consumption of conventional meat, as well as questions about their opinions of cultured meat. We find that, whilst rates of vegetarianism were relatively low in France, unrestricted meat-eaters were a minority in Germany, and concern for animal welfare was the most common reason given for meat reduction. Substantial markets for cultured meat exist in both countries, although German consumers are significantly more open to the concept than the French. Strikingly, cultured meat acceptance is significantly higher amongst agricultural and meat workers, indicating that those who are closest to existing meat production methods are most likely to prefer alternatives. We found some evidence that pro-cultured meat messages, which focus on antibiotic resistance and food safety, are significantly more persuasive than those that focus on animals or the environment. Furthermore, consumers project that they would be significantly more likely to consume cultured meat that does not contain genetically modified ingredients. Overall, we find substantially large markets for cultured meat in Germany and France, and identify some potential ways to further increase acceptance in these markets. We conclude by highlighting the most promising markets for cultured meat, and highlighting a lack of antibiotics as a potentially persuasive message about cultured meat.
How HIV-1 Gag Manipulates Its Host Cell Proteins: A Focus on Interactors of the Nucleocapsid Domain

The human immunodeficiency virus (HIV-1) polyprotein Gag (Group-specific antigen) plays a central role in controlling the late phase of the viral lifecycle. Considered to be only a scaffolding protein for a long time, the structural protein Gag plays determinate and specific roles in HIV-1 replication. Indeed, via its different domains, Gag orchestrates the specific encapsidation of the genomic RNA, drives the formation of the viral particle by its auto-assembly (multimerization), binds multiple viral proteins, and interacts with a large number of cellular proteins that are needed for its functions from its translation location to the plasma membrane, where newly formed virions are released. Here, we review the interactions between HIV-1 Gag and 66 cellular proteins. Notably, we describe the techniques used to evidence these interactions, the different domains of Gag involved, and the implications of these interactions in the HIV-1 replication cycle. In the final part, we focus on the interactions involving the highly conserved nucleocapsid (NC) domain of Gag and detail the functions of the NC interactants along the viral lifecycle.
Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology

Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.