Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Galactose a Hormetic sugar? An Exploratory Study of the Rat Hippocampal Redox Regulatory Network.

SCOPE Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim was to examine the acute effects of oral galactose on the redox regulatory network (RRN). METHODS AND RESULTS Rat plasma and hippocampal RRNs were analyzed upon acute orogastric gavage of galactose (200 mg/kg). No systemic RRN disbalance was observed, however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems was observed in the hippocampus. Galactose-induced increment of reductive capacity was accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. CONCLUSION Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects might be inseparable from its pro-oxidative action at the biochemical level. This article is protected by copyright. All rights reserved.
Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets

The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies.
Dissecting the Genetic Basis of Flowering Time and Height Related-Traits Using Two Doubled Haploid Populations in Maize

In the field, maize flowering time and height traits are closely linked with yield, planting density, lodging resistance, and grain fill. To explore the genetic basis of flowering time and height traits in maize, we investigated six related traits, namely, days to anthesis (AD), days to silking (SD), the anthesis–silking interval (ASI), plant height (PH), ear height (EH), and the EH/PH ratio (ER) in two locations for two years based on two doubled haploid (DH) populations. Based on the two high-density genetic linkage maps, 12 and 22 quantitative trait loci (QTL) were identified, respectively, for flowering time and height-related traits. Of these, ten QTLs had overlapping confidence intervals between the two populations and were integrated into three consensus QTLs (qFT_YZ1a, qHT_YZ5a, and qHT_YZ7a). Of these, qFT_YZ1a, conferring flowering time, is located at 221.1–277.0 Mb on chromosome 1 and explained 10.0–12.5% of the AD and SD variation, and qHT_YZ5a, conferring height traits, is located at 147.4–217.3 Mb on chromosome 5 and explained 11.6–15.3% of the PH and EH variation. These consensus QTLs, in addition to the other repeatedly detected QTLs, provide useful information for further genetic studies and variety improvements in flowering time and height-related traits.
A diagnostic confidence scheme for CLN3 disease

Over the past 20 years, diagnostic testing for genetic diseases has evolved, leading to variable diagnostic certainty for individuals included in long‐term natural history studies. Using genotype and phenotype data from an ongoing natural history study of CLN3 disease, we developed a hierarchical diagnostic confidence scheme with three major classes: Definite, Probable, or Possible CLN3 disease. An additional level, CLN3 Disease PLUS, includes individuals with CLN3 disease plus an additional disorder with a separate etiology that substantially affects the phenotype. Within the Definite and Probable CLN3 disease classes, we further divided individuals into subclasses based on phenotype. After assigning participants to classes, we performed a blinded reclassification to assess the reliability of this scheme. A total of 134 individuals with suspected CLN3 disease were classified: 100 as Definite, 21 as Probable, and 7 as Possible. Six individuals were classified as CLN3‐PLUS. Phenotypes included the classical juvenile‐onset syndromic phenotype, a “vision loss only” phenotype, and an atypical syndromic phenotype. Some individuals were too young to fully classify phenotype. Test‐retest reliability showed 96% agreement. We created a reliable diagnostic confidence scheme for CLN3 disease that has excellent face validity. This scheme has implications for clinical research in CLN3 and other rare genetic neurodegenerative disorders.
Assessing Exposure Hazards and Metal AnalysisResulting from Bauxite Samples Collected froma Saudi Arabian Mine

Since bauxite is a rock consisting of aluminum oxide, it is significant to measure natural radionuclide concentrations for occupational health purposes. The bauxite mine is located in the city of Az Zabirah in the Qassim region in Saudi Arabia. The radionuclide concentrations of 226Ra, 232Th, and 40K in bauxite samples were measured using a γ-ray spectrometer NaI (Tl). The average and range values of 226Ra, 232Th, and 40K radioactivity concentrations were 83.7±0.3 (164.2-35.2), 107.3±1.3 (199.9-48.5), and 192.0±1.1 (487.1-24.6), Bq/kg respectively. These results were compared with published global limits of 226Ra, 232Th, and 40K by (UNSCEAR, 2000; ICRP-60). The radiation hazard parameters were also calculated and compared with the recommended levels. There are no studies for the natural radioactivity in the bauxite mine in Az Zabirah, so these results are a start to establishing a database in this location. Furthermore, x-ray fluorescence (XRF) was used to determine the concentrations of elements and their oxides for the bauxite samples.
Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.
Dynamic Diversity of NLR Genes in Triticum and Mining of Promising NLR Alleles for Disease Resistance

Bread wheat is an essential crop with the second-highest global production after maize. Currently, wheat diseases are a serious threat to wheat production. Therefore, efficient breeding for disease resistance is extremely urgent in modern wheat. Here, we identified 2012 NLR genes from hexaploid wheat, and Ks values of paired syntenic NLRs showed a significant peak at 3.1–6.3 MYA, which exactly coincided with the first hybridization event between A and B genome lineages at ~5.5 MYA. We provided a landscape of dynamic diversity of NLRs from Triticum and Aegilops and found that NLR genes have higher diversity in wild progenitors and relatives. Further, most NLRs had opposite diversity patterns between genic and 2 Kb-promoter regions, which might respectively link sub/neofunctionalization and loss of duplicated NLR genes. Additionally, we identified an alien introgression of chromosome 4A in tetraploid emmer wheat, which was similar to that in hexaploid wheat. Transcriptome data from four experiments of wheat disease resistance helped to profile the expression pattern of NLR genes and identified promising NLRs involved in broad-spectrum disease resistance. Our study provided insights into the diversity evolution of NLR genes and identified beneficial NLRs to deploy into modern wheat in future wheat disease-resistance breeding.
Ansamitocin P3-Loaded Gold-NanoCage Conjugated with Immune Checkpoint Inhibitor to Enhance Photo-Chemo-Thermal Maturation of Dendritic Cells for Hepatocellular Carcinoma

Immunotherapy is a newly developed method for cancer treatment, but still generates limited response in partial patients for hepatocellular carcinoma (HCC) because the immunity cycle is limited by the tumor microenvironment (TME). Herein, we introduce multifunctional gold nanocages (AuNCs)-based nanocarriers with Ansamitocin P3 (AP3) loaded and anti-PDL1 binding (AP3-AuNCs-anti-PDL1) which can combine photothermal therapy, chemotherapeutic agent-triggered DCs maturation, and checkpoint immunotherapy in one platform. The AP3-AuNCs-anti-PDL1 using Avidin-biotin to bind anti-PDL1 on the surface of AP3-AuNCs showed specifically cellular targeting compared to AuNCs, which can increase the immune responses. The AP3-AuNCs+NIR-10 min exhibited the highly activated DCs maturation with two-fold higher than control+NIR, which can be attributed to the significant release of AP3. The results illustrated the synergistic effect of tumor-associated antigens (TAAs) and controlled AP3 release under near infrared (NIR) in triggering effective DCs maturation. Among them, AP3 release played the more important role than the TAAs under PTT in promoting T-cell activation. These results illustrate the promising potential of AuNCs-based nanocarriers combined with AP3 and the checkpoint inhibitors to strengthen the positive loop of immunity cycle.
A Negative Index Nonagonal CSRR Metamaterial-Based Compact Flexible Planar Monopole Antenna for Ultrawideband Applications Using Viscose-Wool Felt

In this paper, a compact textile ultrawideband (UWB) planar monopole antenna loaded with a metamaterial unit cell array (MTMUCA) structure with epsilon-negative (ENG) and near-zero refractive index (NZRI) properties is proposed. The proposed MTMUCA was constructed based on a combination of a rectangular- and a nonagonal-shaped unit cell. The size of the antenna was 0.825 λ0 × 0.75 λ0 × 0.075 λ0, whereas each MTMUCA was sized at 0.312 λ0 × 0.312 λ0, with respect to a free space wavelength of 7.5 GHz. The antenna was fabricated using viscose-wool felt due to its strong metal–polymer adhesion. A naturally available polymer, wool, and a human-made polymer, viscose, that was derived from regenerated cellulose fiber were used in the manufacturing of the adopted viscose-wool felt. The MTMUCA exhibits the characteristics of ENG, with a bandwidth (BW) of 11.68 GHz and an NZRI BW of 8.5 GHz. The MTMUCA was incorporated on the planar monopole to behave as a shunt LC resonator, and its working principles were described using an equivalent circuit. The results indicate a 10 dB impedance fractional bandwidth of 142% (from 2.55 to 15 GHz) in simulations, and 138.84% (from 2.63 to 14.57 GHz) in measurements obtained by the textile UWB antenna. A peak realized gain of 4.84 dBi and 4.4 dBi was achieved in simulations and measurements, respectively. A satisfactory agreement between simulations and experiments was achieved, indicating the potential of the proposed negative index metamaterial-based antenna for microwave applications.
Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Cytomegalovirus (CMV) reactivations represent a significant morbidity and mortality problem in transplant patients. Reliable and rapid measurement of CMV viral load is a key issue for optimal patient management. We report here the evaluation of NeuMoDx™ (Qiagen) in a routine hospital setting (University Hospitals of Marseille, France) in comparison with our classical reference technique R-GENE. During one month, 719 CMV viral loads from 507 patients were measured in parallel in both techniques. Using the ROC (receiver operating characteristic) curve and our biological experience we suggest that values <52 IU/mL (geometric mean) correspond to negative samples, values >140 IU/mL (Fowlkes–Mallows index) correspond to quantifiable positive results and values ranging from 52 to 140 IU/mL represent non-quantifiable positive results. Follow-up of 15 transplant patients who developed CMV reactivation during the study showed that NeuMoDx™ provided higher viral load measurement during the first two weeks of follow-up for three patients. These important intra-individual variations resulted in a significant median increase considering the whole data set (6.7 points of difference expressed as a percentage of the initial viral load). However, no difference between the two techniques was noticeable after two weeks of treatment. Subsequent to this first study we conclude that NeuMoDx™, used with optimized logistics and an adapted threshold, allows a rapid CMV viral load measurement and that its use does not lead to any difference in patient management compared to the reference technique R-GENE®.
Freshmen anxiety and COVID-19: Practical implications from an online intervention for supporting students affected by health inequities

Abstract Objective This study explored how college freshmen, particularly those affected by health inequities, are affected by COVID-19 and whether they would use a university-created online wellness intervention for help. Participants Nine-hundred and eighty-nine freshmen at a large southeastern university. Method Students responded to an online survey regarding their anxiety, worry, number of life disruptions, perceived resilience and their use of the online intervention during the pandemic (June to mid-September 2020). Results During COVID-19, Latinx, Black, women and non-heterosexual students reported significantly greater worry, daily life disruptions than their non-Latinx, white, male and heterosexual counterparts. Women and non-heterosexual students also reported greater anxiety and less resilience. Additionally, Latinx students reported using the university’s online intervention for help during COVID-19 more than others. Overall, freshmen, especially Black and women students, reported the online intervention would help them with struggles. Conclusions Universities should identify unique worries faced by students during a health crisis and provide institutional support. Practical implications are discussed.
Simulating Multi-Scale, Granular Materials and Their Transitions With a Hybrid Euler-Lagrange Solver

Multi-scale granular materials, such as powdered materials and mudslides, are pretty common in nature. Modeling such materials and their phase transitions remains challenging since this task involves the delicate representations of various ranges of particles with multiple scales that cause their property variations among liquid, granular solid (i.e., particles), and smoke-like materials. To effectively animate the complicated yet intriguing natural phenomena involving multi-scale granular materials and their phase transitions in graphics with high fidelity, this article advocates a hybrid Euler-Lagrange solver to handle the behaviors of involved discontinuous fluid-like materials faithfully. At the algorithmic level, we present a unified framework that tightly couples the affine particle-in-cell (APIC) solver with density field to achieve the transformation spanning across granular particles, dust cloud, powders, and their natural mixtures. For example, a part of the granular particles could be transformed into dust cloud while interacting with air and being represented by density field. Meanwhile, the velocity decrease of the involved materials could also result in the transit from the density-field-driven dust to powder particles. Besides, to further enhance our modeling and simulation power to broaden the range of multi-scale materials, we introduce a moisture property for granular particles to control the transitions between particles and viscous liquid. At the geometric level, we devise an additional surface-tracking procedure to simulate the viscous liquid phase. We can arrive at delicate viscous behaviors by controlling the corresponding yield conditions. Through various experiments with the different scenes design being conducted in our unified framework, we can validate the mixed multi-scale materials’ mutual transformation processes. Our unified framework furnished with a hybrid solver can significantly enhance the modeling flexibility and the animation potential of the particle-grid hybrid materials in graphics.
Chitosan-Coated Poly(lactic acid) Nanofibres Loaded with Essential Oils for Wound Healing

Chronic skin wounds are characterised by a non-healing process that makes necessary the application of wound dressings on the damaged area to promote and facilitate the recovery of skin’s physiological integrity. The aim of the present work is to develop a bioactive dressing that, once applied on the injured tissue, would exert antibacterial activity and promote adhesion and proliferation of fibroblasts. Nanofibres consisting of poly(lactic acid) (PLA) and essential oils (EOs) were electrospun and coated with a medium molecular weight chitosan (CS). Black pepper essential oil (BP-EO) or limonene (L), well-known for their antibacterial properties, were added to the PLA/acetone solution before electrospinning; phase separation phenomena occurred due to the poor solubility of the EOs in the PLA solution and led to fibres having surface nano-pores. The porous electrospun fibres were coated with CS to produce hydrophilic membranes that were easy to handle, biocompatible, and suited to promote cellular proliferation. The fibrous scaffolds were tested in terms of mechanical resistance, wettability, antibacterial activity, in-vitro cytotoxicity, and ability to promote fibroblasts’ adhesion and proliferation. The results obtained proved that the CS coating improved the hydrophilicity of the fibrous mats, enhanced EO’s antibacterial potential, and promoted cell adhesion and proliferation.
Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids

The intestinal epithelium critically contributes to oral bioavailability of drugs by constituting an important site for drug absorption and metabolism. In particular, intestinal epithelial cells (IEC) actively serve as gatekeepers of drug and nutrient availability. IECs’ transport processes and metabolism are interrelated to the whole-body metabolic state and represent potential points of origin as well as therapeutic targets for a variety of diseases. Human intestinal organoids represent a superior model of the intestinal epithelium, overcoming limitations of currently used in vitro models. Caco-2 cells or rodent explant models face drawbacks such as their cancer and non-human origin, respectively, but are commonly used to study intestinal nutrient absorption, enterocyte metabolism and oral drug bioavailability, despite poorly correlative data. In contrast, intestinal organoids allow investigating distinct aspects of bioavailability including spatial resolution of transport, inter-individual differences and high-throughput screenings. As several countries have already developed strategic roadmaps to phase out animal experiments for regulatory purposes, intestinal organoid culture and organ-on-a-chip technology in combination with in silico approaches are roads to go in the preclinical and regulatory setup and will aid implementing the 3Rs (reduction, refinement and replacement) principle in basic science.
The Application of Polycaprolactone in Three-Dimensional Printing Scaffolds for Bone Tissue Engineering

Bone tissue engineering commonly encompasses the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the propagation of cells to regenerate damaged tissues or organs. 3D printing technology has been extensively applied to allow direct 3D scaffolds manufacturing. Polycaprolactone (PCL) has been widely used in the fabrication of 3D scaffolds in the field of bone tissue engineering due to its advantages such as good biocompatibility, slow degradation rate, the less acidic breakdown products in comparison to other polyesters, and the potential for loadbearing applications. PCL can be blended with a variety of polymers and hydrogels to improve its properties or to introduce new PCL-based composites. This paper describes the PCL used in developing state of the art of scaffolds for bone tissue engineering. In this review, we provide an overview of the 3D printing techniques for the fabrication of PCL-based composite scaffolds and recent studies on applications in different clinical situations. For instance, PCL-based composite scaffolds were used as an implant surgical guide in dental treatment. Furthermore, future trend and potential clinical translations will be discussed.
Clinically Important Phleboviruses and Their Detection in Human Samples

The detection of phleboviruses (family: Phenuiviridae) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their predominantly nondescript clinical associations, and a related lack of awareness among some clinicians and laboratorians. Here, we seek to inform the detection of human phlebovirus infections by providing a brief introduction to clinically relevant phleboviruses, as well as key targets and approaches for their detection. Given the diversity of pathogens within the genus, this report focuses on diagnostic attributes that are generally shared among these agents and should be used as a complement to, rather than a replacement of, more detailed discussions on the detection of phleboviruses at the individual virus level.