Miracle-dz/UniFAR-FTUs huggingface dataset:
No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis

Abstract Background To test the hypothesis that varicella-zoster virus (VZV) infection contributes to temporal arteritis pathogenesis, comprehensive in situ analysis was performed on temporal artery biopsies of 38 anterior ischemic optic neuropathy (AION) patients, including 14 (37%) with giant cell arteritis. Methods Biopsies were completely sectioned, and, on average, 146 serial sections per patient were stained for VZV glycoprotein E. Results Four of 38 AION patients showed VZV glycoprotein E staining, but VZV infection was not confirmed by staining for VZV IE63 protein and VZV-specific polymerase chain reaction on adjacent sections. Conclusions This study refutes the premise that VZV is casually related to AION with and without giant cell arteritis.
Optimising Non-Patterned MoO3/Ag/MoO3 Anode for High-Performance Semi-Transparent Organic Solar Cells towards Window Applications

Semi-transparent organic solar cells (ST-OSCs) have attracted significant research attention, as they have strong potential to be applied in automobiles and buildings. For ST-OSCs, the transparent top electrode is an indispensable component, where the dielectric/metal/dielectric (D/M/D) structured electrode displayed a promising future due to its simplicity in the fabrication. In this work, by using the MoO3-/Ag-/MoO3-based D/M/D transparent electrode, we fabricated ST-OSCs based on the PM6:N3 active layer for the first time. In the device fabrication, the D/M/D transparent electrode was optimised by varying the thickness of the outer MoO3 layer. As a result, we found that increasing the thickness of the outer MoO3 layer can increase the average visible transmittance (AVT) but decrease the power conversion efficiency (PCE) of the device. The outer MoO3 layer with a 10 nm thickness was found as the optimum case, where its corresponding device showed the PCE of 9.18% with a high AVT of 28.94%. Moreover, the colour perception of fabricated ST-OSCs was investigated. All semi-transparent devices exhibited a neutral colour perception with a high colour rendering index (CRI) over 90, showing great potential for the window application.
Circulating Exosomal miRNAs Signal Circadian Misalignment to Peripheral Metabolic Tissues

Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from the NS condition showed altered Akt phosphorylation responses to insulin in comparison to those treated with exosomes from the DS condition. BMAL1 ChIP-Seq of exosome-treated adipocytes showed 42,037 binding sites in the DS condition and 5538 sites in the NS condition, with a large proportion of BMAL1 targets including genes encoding for metabolic regulators. A significant and restricted miRNA exosomal signature emerged after exposure to the NS condition. Among the exosomal miRNAs regulated differentially after 3 days of simulated NS versus DS, proof-of-concept validation of circadian misalignment signaling was demonstrated with hsa-mir-3614-5p. Exosomes from the NS condition markedly altered expression of key genes related to circadian rhythm in several cultured cell types, including adipocytes, myocytes, and hepatocytes, along with significant changes in 29 genes and downstream gene network interactions. Our results indicate that a simulated NS schedule leads to changes in exosomal cargo in the circulation. These changes promote reduction of insulin sensitivity of adipocytes in vitro and alter the expression of core clock genes in peripheral tissues. Circulating exosomal miRNAs may play an important role in metabolic dysfunction in NS workers by serving as messengers of circadian misalignment to peripheral tissues.
Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability

Abstract The aim of this study was to evaluate the oral bioavailability of liposomal vitamin C and non-liposomal vitamin C in healthy, adult, human subjects under fasting conditions through an open label, randomized, single-dose, two-treatment, two-sequence, two-period, two-way crossover, study. The vitamin C loaded liposome was well characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurements for evaluating morphology, particle size and stabilities, respectively. Microscopic image shows the core-type structure that confirms the characteristic pattern of liposome. The encapsulation efficiency (EE%) and the particle size were 65.85 ± 1.84% and below 100 nm, respectively. The results of the clinical studies of liposomal vitamin C by oral delivery to be 1.77 times more bioavailable than non-liposomal vitamin C. The liposomal vitamin C demonstrated higher values of Cmax, AUC0– t and AUC0-∞ related to non-liposomal vitamin C due to liposomal encapsulation. No adverse events were reported. It could be concluded that liposomal encapsulated ascorbic acid (vitamin C) shows well-organized morphological pattern, uniform particle size and highly efficient, which leads to have enhanced bioavailability.
Childhood Sexual Abuse and Sexual Motivations – The Role of Dissociation

ABSTRACT The present study sought to examine the relations between a history of childhood sexual abuse (CSA) and sexual motivations and to explore the moderating role of dissociation within these relations. The study was conducted among 889 men and women (ages 18–70). Results indicated a history of CSA was significantly related to higher scores on self-affirmation, coping, partner approval and peer pressure sexual motivations. Interactions between CSA and gender in explaining sexual motivations, were not significant. Among participants with a history of CSA (n = 365), dissociation was significantly related to sexual motivations, so that participants who had dissociation scores above the cutoff (reporting high levels of dissociation) scored higher on intimacy, self-affirmation, coping, and partner approval than did those with a history of CSA who reported low levels of dissociation. Analyzes revealed significant moderating effects for dissociation within the relations between CSA and intimacy, coping, and partner approval sexual motivations. The present study suggests CSA survivors and those who report high levels of dissociation in particular, utilize sex for intimacy, for coping with negative emotions, and for partner approval. Therapists working with CSA survivors should be aware of the potential effects the abuse has on the survivor’s reasons to engage in sex.
Genetic relationship between purebred and synthetic pigs for growth performance using single step method

Objective The objective of this study was to estimate the genetic correlation (rpc) of growth performance between purebred (Duroc and Korean native) and synthetic (WooriHeukDon) pigs using a single-step method. Methods Phenotypes of 15,902 pigs with genotyped data from 1,792 pigs from a nucleus farm were used for this study. We estimated the rpc of several performance traits between WooriHeukDon and purebred pigs: day of target weight (DAY), backfat thickness (BF), feed conversion rate (FCR), and residual feed intake (RFI). The variances and covariances of the studied traits were estimated by an animal multi-trait model that applied the Bayesian inference. Results rpc within traits was lower than 0.1 for DAY and BF, but high for FCR and RFI; in particular, rpc for RFI between Duroc and WooriHeukDon pigs was nearly 1. Comparison between different traits revealed that RFI in Duroc pigs was associated with different traits in WooriHeukDon pigs. However, the most of rpc between different traits were estimated with low or with high standard deviation. Conclusion The results indicated that there were substantial differences in rpc of traits in the synthetic WooriHeukDon pigs, which could be caused by these pigs having a more complex origin than other crossbred pigs. RFI was strongly correlated between Duroc and WooriHeukDon pigs, and these breeds might have similar single nucleotide polymorphism effects that control RFI. RFI is more essential for metabolism than other growth traits and these metabolic characteristics in purebred pigs, such as nutrient utilization, could significantly affect those in synthetic pigs. The findings of this study can be used to elucidate the genetic architecture of crossbred pigs and help develop new breeds with target traits.
Separation and HPLC Characterization of Active Natural Steroids in a Standardized Extract from the Serratula coronata Herb with Antiseborrheic Dermatitis Activity

Phytoecdysteroids are natural compounds with therapeutic benefits in both humans and animals. The effectiveness of natural products with health potential is based on the activities and potencies of their active ingredients. In this study, dominant ecdysteroids—ajugasterone C, 20-hydroxyecdysone and polypodine B—from the Serratula coronata (S. coronata) herb were separated by column chromatography, identified by spectroscopic data and quantified by high-performance liquid chromatography with a diode array detector (HPLC-DAD). The obtained concentration of ecdysteroids (approximately 23%) in the S. coronatae herb extract enhances the possibility of their use in pharmaceutical and cosmetic products with high levels of phytoecdysteroids. Moreover, this study has shown a positive effect of ecdysteroids-containing cream on changes in quality of life and a beneficial effect in reducing the symptoms of seborrheic dermatitis. It has been demonstrated that the application of the cream with phytoecdysteroids resulted in a statistically significant alleviation of symptoms (p < 0.05), especially in terms of itching, pain or burning sensations in the affected areas in comparison to previous symptoms.
Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease. Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate. This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.
Mixed Dye Removal Efficiency of Electrospun Polyacrylonitrile–Graphene Oxide Composite Membranes

Exfoliated graphene oxide (GO) was reliably modified with a cetyltrimethylammonium chloride (CTAC) surfactant to greatly improve the dispersity of the GO in a polyacrylonitrile (PAN) polymer precursor solution. Subsequent electrospinning of the mixture readily resulted in the formation of GO–PAN composite nanofibers containing up to 30 wt % of GO as a filler without notable defects. The absence of common electrospinning problems associated with clogging and phase separation indicated the systematic and uniform integration of the GO within the PAN nanofibers beyond the typical limits. After thoroughly examining the formation and maximum loading efficiency of the modified GO in the PAN nanofibers, the resulting composite nanofibers were thermally treated to form membrane-type sheets. The wettability and pore properties of the composite membranes were notably improved with respect to the pristine PAN nanofiber membrane, possibly due to the reinforcing filler effect. In addition, the more GO loaded into the PAN nanofiber membranes, the higher the removal ability of the methylene blue (MB) and methyl red (MR) dyes in the aqueous system. The adsorption kinetics of a mixed dye solution were also monitored to understand how these MB and MR dyes interact differently with the composite nanofiber membranes. The simple surface modification of the fillers greatly facilitated the integration efficiency and improved the ability to control the overall physical properties of the nanofiber-based membranes, which highly impacted the removal performance of various dyes from water.
Electrospun Scaffolds and Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Engineering Applications

Tissue engineering (TE) combines cells, scaffolds, and growth factors to assemble functional tissues for repair or replacement of tissues and organs. Cardiac TE is focused on developing cardiac cells, tissues, and structures—most notably the heart. This review presents the requirements, challenges, and research surrounding electrospun scaffolds and induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) towards applications to TE hearts. Electrospinning is an attractive fabrication method for cardiac TE scaffolds because it produces fibers that demonstrate the optimal potential for mimicking the complex structure of the cardiac extracellular matrix (ECM). iPSCs theoretically offer the capacity to generate limitless numbers of CMs for use in TE hearts, however these iPSC-CMs are electrophysiologically, morphologically, mechanically, and metabolically immature compared to adult CMs. This presents a functional limitation to their use in cardiac TE, and research aiming to address this limitation is presented in this review.
Effect of Laser Rescanning on the Characteristics and Residual Stress of Selective Laser Melted Titanium Ti6Al4V Alloy

The titanium Ti6Al4V alloy has excellent properties, and is one of the most important and widely used metal materials in the field of modern high-tech. Selective laser melting (SLM) is an ideal process for the rapid prototyping of Ti6Al4V alloy components with complex structures, but the performances need to be further improved. In this paper, the relative density, hardness, and microstructure under different scanning conditions were first analyzed in order to clarify the role of rescanning process in improving the performances. Then, the effects of different scanning strategies on the residual stress were analyzed. The results show that the strategy of partition rescanning has the most significant effect on residual stress. Finally, the SLM experiments of aviation nozzle rings were carried out. The results show that the average residual stress of the Re-SLMed sample was reduced from 322 MPa to 254 MPa.
Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

Tuberculosis (TB) is the global leading cause of death from an infectious agent with approximately 10 million new cases of TB and 1.45 million deaths in 2018. Bacille Calmette-Guérin (BCG) remains the only approved vaccine for Mycobacterium tuberculosis (M. tb, causative agent of TB), however clinical studies have shown BCG has variable effectiveness ranging from 0–80% in adults. With 1.7 billion people latently infected, it is becoming clear that vaccine regimens aimed at both post-exposure and pre-exposure to M. tb will be crucial to end the TB epidemic. The two main strategies to improve or replace BCG are subunit and live attenuated vaccines. However, following the failure of the MVA85A phase IIb trial in 2013, more varied and innovative approaches are being developed. These include recombinant BCG strains, genetically attenuated M. tb and naturally attenuated mycobacteria strains, novel methods of immunogenic antigen discovery including for hypervirulent M. tb strains, improved antigen recognition and delivery strategies, and broader selection of viral vectors. This article reviews preclinical vaccine work in the last 5 years with focus on those tested against M. tb challenge in relevant animal models.
Human monoclonal anti-TLR4 antibody negatively regulates lipopolysaccharide-induced inflammatory responses in mouse macrophages

Previous studies have revealed that activation of the Toll-like receptor 4 (TLR4)-mediated proinflammatory signaling pathway plays an important role in acute inflammation, sepsis and chronic inflammatory disorders. Moreover, TLR4 significantly contributes to lipopolysaccharide (LPS)-induced immune response. Thus, modulation of the TLR4 pathway is an important strategy to specifically target these pathologies. The aim of the present study was to develop a complete human anti-TLR4 IgG2 antibody by screening human TLR4 Fab from a phage-display library and integrating it with constant regions of the heavy chain of human IgG2 via antibody engineering. ELISA, a BLItz system and fluorescence-activated cell sorting were used to assess its affinity. Furthermore, mouse-derived peritoneal macrophages were treated with human anti-TLR4 IgG2 and induced with LPS in vitro. Reverse transcription-quantitative PCR and western blotting were used to determine mRNA expression levels of cytokines and phosphorylation levels of signaling pathways, respectively. It was found that human anti-TLR4 IgG2 bound to TLR4 with a high affinity of 8.713×10−10 M, and that preincubation with anti-TLR4 IgG2 inhibited the LPS-induced production of tumor necrosis factor-α, interferon-β and interleukin-6 mRNA expression levels in mouse peritoneal macrophages. It was also demonstrated that human anti-TLR4 IgG2 inhibited LPS-induced TLR4 signaling by reducing the phosphorylation of the NF-κB, mitogen-activated protein kinase and interferon regulatory factor 3 signaling pathways. In addition, human anti-TLR4 IgG2 protected mice from LPS challenge with a survival rate of 40% and also significantly increased the survival time in the cecal ligation and puncture model. Therefore, it was speculated that human anti-TLR4 IgG2 plays a protective role against sepsis-associated injury and is potentially applicable for the treatment of infection-associated immune dysfunction.
The Utility of Resolving Asthma Molecular Signatures Using Tissue-Specific Transcriptome Data

An integrative analysis focused on multi-tissue transcriptomics has not been done for asthma. Tissue-specific DEGs remain undetected in many multi-tissue analyses, which influences identification of disease-relevant pathways and potential drug candidates. Transcriptome data from 609 cases and 196 controls, generated using airway epithelium, bronchial, nasal, airway macrophages, distal lung fibroblasts, proximal lung fibroblasts, CD4+ lymphocytes, CD8+ lymphocytes from whole blood and induced sputum samples, were retrieved from Gene Expression Omnibus (GEO). Differentially regulated asthma-relevant genes identified from each sample type were used to identify (a) tissue-specific and tissue–shared asthma pathways, (b) their connection to GWAS-identified disease genes to identify candidate tissue for functional studies, (c) to select surrogate sample for invasive tissues, and finally (d) to identify potential drug candidates via connectivity map analysis. We found that inter-tissue similarity in gene expression was more pronounced at pathway/functional level than at gene level with highest similarity between bronchial epithelial cells and lung fibroblasts, and lowest between airway epithelium and whole blood samples. Although public-domain gene expression data are limited by inadequately annotated per-sample demographic and clinical information which limited the analysis, our tissue-resolved analysis clearly demonstrated relative importance of unique and shared asthma pathways, At the pathway level, IL-1b signaling and ERK signaling were significant in many tissue types, while Insulin-like growth factor and TGF-beta signaling were relevant in only airway epithelial tissue. IL-12 (in macrophages) and Immunoglobulin signaling (in lymphocytes) and chemokines (in nasal epithelium) were the highest expressed pathways. Overall, the IL-1 signaling genes (inflammatory) were relevant in the airway compartment, while pro-Th2 genes including IL-13 and STAT6 were more relevant in fibroblasts, lymphocytes, macrophages and bronchial biopsies. These genes were also associated with asthma in the GWAS catalog. Support Vector Machine showed that DEGs based on macrophages and epithelial cells have the highest and lowest discriminatory accuracy, respectively. Drug (entinostat, BMS-345541) and genetic perturbagens (KLF6, BCL10, INFB1 and BAMBI) negatively connected to disease at multi-tissue level could potentially repurposed for treating asthma. Collectively, our study indicates that the DEGs, perturbagens and disease are connected differentially depending on tissue/cell types. While most of the existing literature describes asthma transcriptome data from individual sample types, the present work demonstrates the utility of multi-tissue transcriptome data. Future studies should focus on collecting transcriptomic data from multiple tissues, age and race groups, genetic background, disease subtypes and on the availability of better-annotated data in the public domain.