Miracle-dz/UniFAR-FTUs huggingface dataset:
Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens

Yearly, about 1.5 million people become chronically infected with hepatitis C virus (HCV) and for the 71 million with chronic HCV infection about 400,000 die from related morbidities, including liver cirrhosis and cancer. Effective treatments exist, but challenges including cost-of-treatment and wide-spread undiagnosed infection, necessitates the development of vaccines. Vaccines should induce neutralizing antibodies (NAbs) against the HCV envelope (E) transmembrane glycoprotein 2, E2, which partly depends on its interaction partner, E1, for folding. Here, we generated three soluble HCV envelope protein antigens with the transmembrane regions deleted (i.e., fused peptide backbones), termed sE1E2 (E1 followed by E2), sE2E1 (E2 followed by E1), and sE21E (E2 followed by inverted E1). The E1 inversion for sE21E positions C-terminal residues of E1 near C-terminal residues of E2, which is in analogy to how they likely interact in native E1/E2 complexes. Probing conformational E2 epitope binding using HCV patient-derived human monoclonal antibodies, we show that sE21E was superior to sE2E1, which was consistently superior to sE1E2. This correlated with improved induction of NAbs by sE21E compared with sE2E1 and especially compared with sE1E2 in female BALB/c mouse immunizations. The deletion of the 27 N-terminal amino acids of E2, termed hypervariable region 1 (HVR1), conferred slight increases in antigenicity for sE2E1 and sE21E, but severely impaired induction of antibodies able to neutralize in vitro viruses retaining HVR1. Finally, comparing sE21E with sE2 in mouse immunizations, we show similar induction of heterologous NAbs. In summary, we find that C-terminal E2 fusion of E1 or 1E is superior to N-terminal fusion, both in terms of antigenicity and the induction of heterologous NAbs. This has relevance when designing HCV E1E2 vaccine antigens.
A New Lectin from Auricularia auricula Inhibited the Proliferation of Lung Cancer Cells and Improved Pulmonary Flora

Lectins are widely distributed in the natural world and are usually involved in antitumor activities. Auricularia auricula (A. auricula) is a medicinal and edible homologous fungus. A. auricula contains many active ingredients, such as polysaccharides, melanin, flavonoids, adenosine, sterols, alkaloids, and terpenes. In this study, we expected to isolate and purify lectin from A. auricula, determine the glycoside bond type and sugar-specific protein of A. auricula lectin (AAL), and finally, determine its antitumor activities. We used ammonium sulfate fractionation, ion exchange chromatography, and affinity chromatography to separate and purify lectin from A. auricula. The result was a 25 kDa AAL with a relative molecular mass of 18913.22. Protein identification results suggested that this lectin contained four peptide chains by comparing with the UniProt database. The FT-IR and β-elimination reaction demonstrated that the connection between the oligosaccharide and polypeptide of AAL was an N-glucoside bond. Analyses of its physical and chemical properties showed that AAL was a temperature-sensitive and acidic/alkaline-dependent glycoprotein. Additionally, the anticancer experiment manifested that AAL inhibited the proliferation of A549, and the IC50 value was 28.19 ± 1.92 μg/mL. RNA sequencing dataset analyses detected that AAL may regulate the expression of JUN, TLR4, and MYD88 to suppress tumor proliferation. Through the pulmonary flora analysis, the bacterial structure of each phylum in the lectin treatment group was more reasonable, and the colonization ability of the normal microflora was improved, indicating that lectin treatment could significantly improve the bacterial diversity characteristics.
Huxie Huaji Ointment Induced Apoptosis of Liver Cancer Cells In Vivo and In Vitro by Activating the Mitochondrial Pathway

Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.
Analysis of Blood Biochemistry of Free Ranging and Human-Managed Southern White Rhinoceros (Ceratotherium simum simum) Using the i-STAT Alinity v®

Handheld point-of-care blood analyzers deliver rapid results for biochemical and hematologic parameters, making them very useful in veterinary clinics and in fieldwork applications. This study compared the biochemical and hematologic parameters generated by the novel point-of-care analyzer i-STAT® Alinity V CHEM8+ cartridge between human-managed and free ranging populations of southern white rhinoceros (Ceratotherium simum simum). In addition, a novel reference interval for ionized calcium (iCa), a parameter of diagnostic and prognostic importance, was established for southern white rhinoceros. Blood samples were obtained from 10 managed (6 at NC Zoo and 4 at Busch Gardens Tampa Bay in 2019) and 30 free ranging white rhinoceros (collected in South Africa between 2018 and 2019) and analyzed using the i-STAT. Multiple parameters were higher (P < 0.05) in free ranging versus managed animals including potassium, blood urea nitrogen, creatinine, glucose, hematocrit, and hemoglobin. Conversely, iCa concentrations were higher (P < 0.05) in the managed populations of white rhinoceros. The RI determined for iCa was 1.36–1.56 mmol/L, with a mean of 1.46 mmol/L, and was determined using the guidelines from the American Society for Veterinary Clinical Pathology. There was no difference in anion gap, chlorine, total carbon dioxide, or sodium between the populations. Seasonality and locality of sampling as well as diet may be contributing factors to the higher iCa concentrations in managed rhinoceros. The six elevated parameters in free ranging rhinoceros are likely attributable to dehydration compounded by capture stress. This data provides insight into the state of several biochemical and hematologic parameters in southern white rhinoceros and will allow veterinarians to better assess the health of both managed and free ranging populations.
Phytomedicine from Middle Eastern Countries: An Alternative Remedy to Modern Medicine against Candida spp Infection

Candida spp are capable of infecting both normal and immunocompromised individuals. More recently, Candida infections have spread considerably in healthcare settings, especially in intensive care units, where it is the most frequently encountered pathogen. Candida albicans is the commonest species encountered, although infections by non-albicans species have also risen in the past few years. The pathogenicity of Candida is credited to its aptitude to change between yeast and hyphal modes of growth. Candida spp produce biofilms on synthetic materials that protect them and facilitate drug resistance and act as a source for chronic and recurrent infections. Primarily, azoles antifungal agents are utilized to treat Candida infection that targets the ergosterol synthesis pathway in the cell wall. The development of antifungal resistance in Candida species is a major reason for treatment failure, and hence, there is a need to develop newer antifungal molecules and/or modifications of existing antifungals to make them more effective and less toxic. This has led researchers to oversee the plants to discover newer antimicrobials. Middle Eastern countries are well known for their landscape ranging from dry and sandy deserts to snow-capped mountains. However, they comprise enormous plant diversity with over 20,000 different species showing various types of bioactivities, such as anticancer, antidiabetic, and antimicrobial activities. Especially, the antifungal potential of these phytoproducts could be exploited in the clinical setting for therapy. The present review examines some of the promising alternative natural compounds that have been tested and found effective in treating Candida infections in vitro in some Middle Eastern countries.
Coarse-Grained Modeling of Polystyrene in Various Environments by Iterative Boltzmann Inversion

We have developed mesoscale models for polystyrene (PS) oligomers in various environments following the Iterative Boltzmann Inversion Technique. Bond, bending angle, torsion angle distributions, and radial distribution functions between PS monomers show that local structures were reproduced very well, while a small discrepancy remained in the reproduction of global structures (radii of gyration and end-to-end distances), which is probably due to end effects. Speedup in polymer dynamics with each model was monitored by scaling factors calculated based on characteristic relaxation times of the end monomers as well as diffusivities of the chains. Results show that coarse-graining is most successful for the highest concentration system (melt) and least for the lowest concentration (dilute solution) due to the stronger slowdown of diffusive and rotational dynamics in atomistic simulations with concentration. The speedup in the confined solution system was found to be greater than in the unconfined solution sys.
Improved Neural Network Generalization using Channel-Wise NNK Graph Constructions

State-of-the-art neural network architectures continue to scale in size and deliver impressive results on unseen data points at the expense of poor interpretability. In the deep layers of these models we often encounter very high dimensional feature spaces, where constructing graphs from intermediate data representations can lead to the well-known curse of dimensionality. We propose a channel-wise graph construction method that works on lower dimensional subspaces and provides a new channel-based perspective that leads to better interpretability of the data and relationship between channels. In addition, we introduce a novel generalization estimate based on the proposed graph construction method with which we perform local polytope interpolation. We show its potential to replace the standard generalization estimate based on validation set performance to perform progressive channel-wise early stopping without requiring a validation set.
Professional Development and Teaching Practices of EFL Palestinian Teachers during COVID-19 Pandemic: A Case Study of Three Female Teachers

The current study investigated the activities and practices used by three female EFL teachers during the coronavirus pandemic between March 2020 till February 2021. The study also explored the difficulties and obstacles faced by the three teachers during that period. To achieve these objectives, a qualitative approach utilizing a case study design was employed using three tools: teachers’ written reflections, content analysis of teachers’ posts on the social media, and a focus group meeting via Zoom. The significance of the study emerges from its objectives to contribute to EFL teachers’ professional development during the emergency cases. Results revealed that the three teachers were able to cope with the new situation by adopting new methods of content delivery and new forms of communication as well. These teachers used online technologies such as Facebook, YouTube, and Microsoft Teams to communicate with their students and the parents as well. However, some challenges emerged, including the financial situation of the families and its impact on students’ access to internet connection and family affordability. Under these conditions, teacher training programs are in demand for using appropriate technologies that engage the students and attract their attention.
Fluorescent microscopy in the nucleus: Investigating protein diffusion and binding in live cells

RESEARCH AND PROJECT MANAGEMENT EXPERIENCE Institute for Biophysical Dynamics, University of Chicago (Chicago, IL) December 2013 – Present Post-doctoral Scholar, Prof. Norbert Scherer § Oversees a group confocal microscope, hardware and software configuration, and training o Publications in Nature Microbiology & Review of Scientific Instruments § Developed snapshot microscopy imaging technologies combining improved 3D field of view and super-resolution § Supervised three undergraduate research assistants
Web-Based Medical Examinations During the COVID-19 Era: Reconsidering Learning as the Main Goal of Examination

Like other aspects of the health care system, medical education has been greatly affected by the COVID-19 pandemic. To follow the requirements of lockdown and virtual education, the performance of students has been evaluated via web-based examinations. Although this shift to web-based examinations was inevitable, other mental, educational, and technical aspects should be considered to ensure the efficiency and accuracy of this type of evaluation in this era. The easiest way to address the new challenges is to administer traditional questions via a web-based platform. However, more factors should be accounted for when designing web-based examinations during the COVID-19 era. This article presents an approach in which the opportunity created by the pandemic is used as a basis to reconsider learning as the main goal of web-based examinations. The approach suggests using open-book examinations, using questions that require high cognitive domains, using real clinical scenarios, developing more comprehensive examination blueprints, using advanced platforms for web-based questions, and providing feedback in web-based examinations to ensure that the examinees have acquired the minimum competency levels defined in the course objectives.
Demystifying emerging bulk RNA-Seq applications: the application and utility of bioinformatic methodology

Significant innovations in next-generation sequencing techniques and bioinformatics tools have impacted our appreciation and understanding of RNA. Practical RNA sequencing (RNA-Seq) applications have evolved in conjunction with sequence technology and bioinformatic tools advances. In most projects, bulk RNA-Seq data is used to measure gene expression patterns, isoform expression, alternative splicing and single-nucleotide polymorphisms. However, RNA-Seq holds far more hidden biological information including details of copy number alteration, microbial contamination, transposable elements, cell type (deconvolution) and the presence of neoantigens. Recent novel and advanced bioinformatic algorithms developed the capacity to retrieve this information from bulk RNA-Seq data, thus broadening its scope. The focus of this review is to comprehend the emerging bulk RNA-Seq-based analyses, emphasizing less familiar and underused applications. In doing so, we highlight the power of bulk RNA-Seq in providing biological insights.
Morphology and surface structure of nanocarbon allotropes: A comparative study

ABSTRACT Different carbon allotropes, including vulcan carbon, multiwall carbon nanotubes, graphene, and nanodiamonds, were processed by chemical purification and treated in a mixture of H2SO4–HNO3. The materials were characterized by infrared and Raman spectroscopy as well as by scanning and transmission electron microscopy. Oxidative differences are indicated by Raman through the G band (∼1570 cm−1), D band (∼1340 cm−1), and G’ band (∼2684 cm−1). The crystal size (La) and purity, relative to the amorphous carbonaceous material, were studied as well, along with the morphological changes induced by the treatments.
Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease

Synapse degeneration in Alzheimer's disease (AD) correlates strongly with cognitive decline. There is well‐established excitatory synapse loss in AD with known contributions of pathological amyloid beta (Aβ) to excitatory synapse dysfunction and loss. Despite clear changes in circuit excitability in AD and model systems, relatively little is known about pathology in inhibitory synapses.
Non-invasive characterization of pleural and pericardial effusions using T1 mapping by magnetic resonance imaging.

AIMS Differentiating exudative from transudative effusions is clinically important and is currently performed via biochemical analysis of invasively obtained samples using Light's criteria. Diagnostic performance is however limited. Biochemical composition can be measured with T1 mapping using cardiovascular magnetic resonance (CMR) and hence may offer diagnostic utility for assessment of effusions. METHODS AND RESULTS A phantom consisting of serially diluted human albumin solutions (25-200 g/L) was constructed and scanned at 1.5 T to derive the relationship between fluid T1 values and fluid albumin concentration. Native T1 values of pleural and pericardial effusions from 86 patients undergoing clinical CMR studies retrospectively analysed at four tertiary centres. Effusions were classified using Light's criteria where biochemical data was available (n = 55) or clinically in decompensated heart failure patients with presumed transudative effusions (n = 31). Fluid T1 and protein values were inversely correlated both in the phantom (r = -0.992) and clinical samples (r = -0.663, P < 0.0001). T1 values were lower in exudative compared to transudative pleural (3252 ± 207 ms vs. 3596 ± 213 ms, P < 0.0001) and pericardial (2749 ± 373 ms vs. 3337 ± 245 ms, P < 0.0001) effusions. The diagnostic accuracy of T1 mapping for detecting transudates was very good for pleural and excellent for pericardial effusions, respectively [area under the curve 0.88, (95% CI 0.764-0.996), P = 0.001, 79% sensitivity, 89% specificity, and 0.93, (95% CI 0.855-1.000), P < 0.0001, 95% sensitivity; 81% specificity]. CONCLUSION Native T1 values of effusions measured using CMR correlate well with protein concentrations and may be helpful for discriminating between transudates and exudates. This may help focus the requirement for invasive diagnostic sampling, avoiding unnecessary intervention in patients with unequivocal transudative effusions.
Development and Application of an interactive Physiologically Based Pharmacokinetic (iPBPK) Model to Predict Oxytetracycline Tissue Distribution and Withdrawal Intervals in Market-Age Sheep and Goats.

Oxytetracycline (OTC) is a widely used antibiotic in food-producing animals. Extralabel use of OTC is common and may lead to violative residues in edible tissues. It is important to have a quantitative tool to predict scientifically-based withdrawal intervals (WDIs) after extralabel use in food animals to ensure human food safety. This study focuses on developing a physiologically based pharmacokinetic (PBPK) model for OTC in sheep and goats. The model included seven compartments: plasma, lung, liver, kidneys, muscle, fat, and rest of the body. The model was calibrated with serum and tissue (liver, muscle, kidney, and fat) concentration data following a single intramuscular (IM, 20 mg/kg) and/or intravenous (IV, 10 mg/kg) administration of a long-acting formulation in sheep and goats. The model was evaluated with independent datasets from Food Animal Residue Avoidance Databank (FARAD). Results showed that the model adequately simulated the calibration datasets with an overall estimated coefficient of determination (R2) of 0.95 and 0.92, respectively, for sheep and goat models and had acceptable accuracy for the validation datasets. Monte Carlo sampling technique was applied to predict the time needed for drug concentrations in edible tissues to fall below tolerances for the 99th percentiles of the population. The model was converted to a web-based interactive PBPK (iPBPK) interface to facilitate model applications. This iPBPK model provides a useful tool to estimate WDIs for OTC after extralabel use in small ruminants to ensure food safety and serves as a basis for extrapolation to other tetracycline drugs and other food animals.
Specific electromagnetic radiation in the wireless signal range increases wakefulness in mice

Significance The steady increase of electromagnetic radiation (EMR) in the environment, particularly the wireless signal, causes serious public concern over its potential negative impact on health. However, it is challenging to examine such impact on human subjects due to associated complex issues. In this study, we establish an experimental system for the investigation of EMR impact on mice. Using this system, we uncovered a causal relationship between 2.4-GHz EMR modulated by 100-Hz square pulses and increased wakefulness in mice. This result identifies sleep alteration as a potential consequence of exposure to excessive wireless signals. Electromagnetic radiation (EMR) in the environment has increased sharply in recent decades. The effect of environmental EMR on living organisms remains poorly characterized. Here, we report the impact of wireless-range EMR on the sleep architecture of mouse. Prolonged exposure to 2.4-GHz EMR modulated by 100-Hz square pulses at a nonthermal output level results in markedly increased time of wakefulness in mice. These mice display corresponding decreased time of nonrapid eye movement (NREM) and rapid eye movement (REM). In contrast, prolonged exposure to unmodulated 2.4-GHz EMR at the same time-averaged output level has little impact on mouse sleep. These observations identify alteration of sleep architecture in mice as a specific physiological response to prolonged wireless-range EMR exposure.