Miracle-dz/UniFAR-FTUs huggingface dataset:
Encapsulation of beetroot juice: a study on the application of pumpkin oil cake protein as new carrier agent

Abstract Aim: In the present study, beetroot juice was encapsulated in pumpkin protein isolate by freeze and spray drying method. Methods: The powders were characterised by measuring moisture content, hygroscopicity, bulk density, solubility, a* value (colour). To simulate the human gastrointestinal digestion, in vitro digestion was conducted as two-stage hydrolysis by pepsin and by pancreatin. The antioxidant and ACE inhibitory potential of the digests was examined. Results: Encapsulation efficiency of phenols from beetroot juice in pumpkin protein isolate was 92% for freeze and 75% for spray dried. Physical properties of all samples were affected by the drying methods. All powders were easily digested. It was observed that the antioxidant and ACE inhibitory potential of the digests was enhanced, indicating that it originated from the hydrolysates released from the protein carrier during digestion. Conclusion: The results from this study are promising and indicate that the pumpkin oil cake protein has great potential and could be introduced to the encapsulation process of bioactive compounds as a new carrier agent.
The α9 Nicotinic Acetylcholine Receptor Mediates Nicotine-Induced PD-L1 Expression and Regulates Melanoma Cell Proliferation and Migration

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR). α9-nAChR overexpression in melanoma using melanoma cell lines, human melanoma tissues, and assessment of publicly available databases. α9-nAChR expression was significantly correlated with PD-L1 expression, clinical stage, lymph node status, and overall survival (OS). Overexpressing or knocking down α9-nAChR in melanoma cells up- or downregulated PD-L1 expression, respectively, and affected melanoma cell proliferation and migration. Nicotine-induced α9-nAChR activity promoted melanoma cell proliferation through stimulation of the α9-nAChR-mediated AKT and ERK signaling pathways. In addition, nicotine-induced α9-nAchR activity promoted melanoma cell migration via activation of epithelial-mesenchymal transition (EMT). Moreover, PD-L1 expression was upregulated in melanoma cells after nicotine treatment via the transcription factor STAT3 binding to the PD-L1 promoter. These results highlight that nicotine-induced α9-nAChR activity promotes melanoma cell proliferation, migration, and PD-L1 upregulation. This study may reveal important insights into the mechanisms underlying nicotine-induced melanoma growth and metastasis through α9-nAChR-mediated carcinogenic signals and PD-L1 expression.
Exploring the binding mechanism of saccharin and sodium saccharin to promoter of human p53 gene by theoretical and experimental methods

Abstract In the past few decades, extensive discussions have been on the impact of artificial sweeteners on the risk of cancer. The present study aimed to evaluate the interaction of saccharin (SA) and sodium saccharin (SSA) with the promoter of the human p53 gene. The binding ability was assessed using the spectroscopic technique, molecular docking and molecular dynamics (MD) simulation methods. Free energy of binding has been calculated using Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Fluorescence spectra of mentioned gene with concentration profiles of SA and SSA were obtained in a physiological condition. A gradual increase without any significant spectral shift in the fluorescence intensity of around 350 nm was evident, indicating the presence of an interaction between both compounds and gene. The docking results showed that both compounds were susceptible to bind to 5′-DG56DG57-3′ nucleotide sequence of gene. Furthermore, the MD simulation demonstrated that the binding positions for SA and SSA were 5′-A1T3T4-3′ and 5′-G44T45-3′ sequences of gene, respectively. The binding of these sweeteners to gene made significant conformational changes to the DNA structure. Hydrogen and hydrophobic interactions are the major forces in complexes stability. Through the groove binding mode, the non-interactive DNA-binding nature of SSA and SA has been demonstrated by the results of spectrofluorometric and molecular modeling. This study could provide valuable insight into the binding mechanism of SA and its salt with p53 gene promoter as macromolecule at the molecular level in atomistic details. This work can contribute to the possibility of the potential hazard of carcinogenicity of this sweetener and to design and apply new and safer artificial sweeteners. AbbreviationsSA SaccharinSSA Sodium SaccharinPp53g promoter of human p53 geneMD Molecular dynamicsRMSD Root-mean-square deviationRMSF Root-mean-square fluctuationRg Radius of GyrationSASA Solvent-Accessible Surface AreaADI Acceptable daily intakeMM/PBSA Molecular Mechanics/Poisson–Boltzmann Surface Area Communicated by Ramaswamy H. Sarma
Flavanol Polymerization Is a Superior Predictor of α-Glucosidase Inhibitory Activity Compared to Flavanol or Total Polyphenol Concentrations in Cocoas Prepared by Variations in Controlled Fermentation and Roasting of the Same Raw Cocoa Beans

Raw cocoa beans were processed to produce cocoa powders with different combinations of fermentation (unfermented, cool, or hot) and roasting (not roasted, cool, or hot). Cocoa powder extracts were characterized and assessed for α-glucosidase inhibitory activity in vitro. Cocoa processing (fermentation/roasting) contributed to significant losses of native flavanols. All of the treatments dose-dependently inhibited α-glucosidase activity, with cool fermented/cool roasted powder exhibiting the greatest potency (IC50: 68.09 µg/mL), when compared to acarbose (IC50: 133.22 µg/mL). A strong negative correlation was observed between flavanol mDP and IC50, suggesting flavanol polymerization as a marker of enhanced α-glucosidase inhibition in cocoa. Our data demonstrate that cocoa powders are potent inhibitors of α-glucosidase. Significant reductions in the total polyphenol and flavanol concentrations induced by processing do not necessarily dictate a reduced capacity for α-glucosidase inhibition, but rather these steps can enhance cocoa bioactivity. Non-traditional compositional markers may be better predictors of enzyme inhibitory activity than cocoa native flavanols.
A New Advanced Encryption Standard-Butterfly Effect in Protecting Image of Copyright Piracy

Cryptography is growing every day where secure communication on the internet is very much concerned. Encryption is a very hot topic when it comes to keeping the data security and integrity. Several photographic images are published to particular interests which makes it more prone to copyright piracy of images. This paper presents a novelty on Advanced Encryption Standard (AES) algorithm with Butterfly Effect (BE) implementation which is imperative in protecting the copyright of the digital image. The study is implemented and simulated using PHP. This study is analyzed using the five metrics namely the visual analysis, file size, luminosity histogram, comparison by pixel, and hamming distance. In the file sizes, there are variations in the size of file where it shows that the average value of the percentage changes to -23.85% from the original to the encrypted image and -1.45% percentage value from the original to the decrypted image. This proves that there is a change in the primary data encryption and decryption process. However, the zero results in the hamming distance indicate that there is no changes in the image from the original until it is being encrypted and decrypted. In the histogram analysis, it yields a match or the same result from the original, encrypted and decrypted file which interprets that the image did not changed. From these results, AES-BE encryption techniques can be used for copyright protection of the image.
Proliferation and AKT Activity Biomarker Analyses after Capivasertib (AZD5363) Treatment of Patients with ER+ Invasive Breast Cancer (STAKT)

Purpose: The STAKT study examined short-term exposure (4.5 days) to the oral selective pan-AKT inhibitor capivasertib (AZD5363) to determine if this drug can reach its therapeutic target in sufficient concentration to significantly modulate key biomarkers of the AKT pathway and tumor proliferation. Patients and Methods: STAKT was a two-stage, double-blind, randomized, placebo-controlled, “window-of-opportunity” study in patients with newly diagnosed ER+ invasive breast cancer. Stage 1 assessed capivasertib 480 mg b.i. d. (recommended monotherapy dose) and placebo, and stage 2 assessed capivasertib 360 and 240 mg b.i. d. Primary endpoints were changes from baseline in AKT pathway markers pPRAS40, pGSK3β, and proliferation protein Ki67. Pharmacologic and pharmacodynamic properties were analyzed from blood sampling, and tolerability by adverse-event monitoring. Results: After 4.5 days' exposure, capivasertib 480 mg b.i. d. (n = 17) produced significant decreases from baseline versus placebo (n = 11) in pGSK3β (H-score absolute change: −55.3, P = 0.006) and pPRAS40 (−83.8, P < 0.0001), and a decrease in Ki67 (absolute change in percentage positive nuclei: −9.6%, P = 0.031). Significant changes also occurred in secondary signaling biomarker pS6 (−42.3, P = 0.004), while pAKT (and nuclear FOXO3a) also increased in accordance with capivasertib's mechanism (pAKT: 81.3, P = 0.005). At doses of 360 mg b.i. d. (n = 5) and 240 mg b.i. d. (n = 6), changes in primary and secondary biomarkers were also observed, albeit of smaller magnitude. Biomarker modulation was dose and concentration dependent, and no new safety signals were evident. Conclusions: Capivasertib 480 mg b.i. d. rapidly modulates key biomarkers of the AKT pathway and decreases proliferation marker Ki67, suggesting future potential as an effective therapy in AKT-dependent breast cancers.
Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target

ABSTRACT Introduction: Tumor necrosis factor (TNF) receptor 2 (TNFR2) is one of two receptors of the cytokines, TNF and lymphotoxin-α. TNFR1 is a strong inducer of proinflammatory activities. TNFR2 has proinflammatory effects too, but it also elicits strong anti-inflammatory activities and has protective effects on oligodendrocytes, cardiomyocytes, and keratinocytes. The protective and anti-inflammatory effects of TNFR2 may explain why TNF inhibitors failed to be effective in diseases such as heart failure or multiple sclerosis, where TNF has been strongly implicated as a driving force. Stimulatory and inhibitory TNFR2 targeting hence attracts considerable interest for the treatment of autoimmune diseases and cancer. Areas covered: Based on a brief description of the pathophysiological importance of the TNF-TNFR1/2 system, we discuss the potential applications of TNFR2 targeting therapies. We also debate TNFR2 activation as a way forward in the search for TNFR2-specific agents. Expert opinion: The use of TNFR2 to target regulatory T-cells is attractive, but this approach is just one amongst many suitable targets. With respect to its preference for Treg stimulation and protection of non-immune cells, TNFR2 is more unique and thus offers opportunities for translational success.
Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming

Forced transcription factor expression can transdifferentiate somatic cells into other specialised cell types or reprogram them into induced pluripotent stem cells (iPSCs) with variable efficiency. To better understand the heterogeneity of these processes, we used single-cell RNA sequencing to follow the transdifferentation of murine pre-B cells into macrophages as well as their reprogramming into iPSCs. Even in these highly efficient systems, there was substantial variation in the speed and path of fate conversion. We predicted and validated that these differences are inversely coupled and arise in the starting cell population, with Mychigh large pre-BII cells transdifferentiating slowly but reprogramming efficiently and Myclow small pre-BII cells transdifferentiating rapidly but failing to reprogram. Strikingly, differences in Myc activity predict the efficiency of reprogramming across a wide range of somatic cell types. These results illustrate how single cell expression and computational analyses can identify the origins of heterogeneity in cell fate conversion processes.
Association of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects

Mishra et al. present a composite extreme-phenotype strategy for gene mapping of cerebral small vessel disease in population cohorts of older persons. They identify associations with variants in HTRA1 and NOTCH3, and describe two participants heterozygous for known pathogenic variants for familial small vessel disease in NOTCH3 and HTRA1.
The Stability of Temperament from Early Childhood to Early Adolescence: A Multi–Method, Multi–Informant Examination

Temperament is a core aspect of children's psychological functioning and is assumed to be at least somewhat stable across childhood. However, little research has assessed the stability of temperament from early childhood to early adolescence. Moreover, few studies have examined the influence of measurement and analytic methods on the stability of early temperament over periods of more than a few years. We obtained laboratory observations and mother and father reports of temperamental negative and positive emotionality and effortful control from 559 three–year–olds. Approximately nine years later, children and both parents completed questionnaire measures of similar temperament constructs. Zero–order correlations revealed greater within–informant than cross–informant stability. In addition, compared with parent reports, early childhood laboratory measures showed greater convergent and divergent validity with child, mother, and father reports at age 12. Finally, latent temperament variables at age 3 composed of laboratory and parent–report measures and latent variables at age 12 composed of parent and child reports showed moderate stability. There was also a weak but significant association of early effortful control with later negative and positive emotionality. Results have implications for assessing temperament and knowledge of the stability of temperament across childhood. Copyright © 2018 European Association of Personality Psychology
Uncovering the Turnover Intention of Proactive Employees: The Mediating Role of Work Engagement and the Moderated Mediating Role of Job Autonomy

Retaining proactive employees with the potential to be high performers is recognized as an essential condition for an organization’s survival and prosperity. However, few studies have logically explained and empirically clarified the link between proactive personality, which represents a distal proactive tendency, and turnover intention to predict actual turnover behavior. With the research objective to address these research gaps, we expected that work engagement as a proximal motivational mechanism was likely to mediate the relationship between proactive personality and turnover intention, and that job autonomy as a critical job context was likely to moderate the relationship between proactive personality and work engagement. We developed a moderated mediation model incorporating these expectations. The results of the survey conducted on employees working for mid-sized manufacturing firms in Korea were consistent with our expectations. The findings of this study help uncover the intentions of turnover exhibited by proactive employees.
Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culture†

Abstract Germline stem and progenitor cells can be extracted from the adult mouse testis and maintained long-term in vitro. Yet, the optimal culture conditions for preserving stem cell activity are unknown. Recently, multiple members of the Eph receptor family were detected in murine spermatogonia, but their roles remain obscure. One such gene, Ephb2, is crucial for maintenance of somatic stem cells and was previously found enriched at the level of mRNA in murine spermatogonia. We detected Ephb2 mRNA and protein in primary adult spermatogonial cultures and hypothesized that Ephb2 plays a role in maintenance of stem cells in vitro. We employed CRISPR-Cas9 targeting and generated stable mutant SSC lines with complete loss of Ephb2. The characteristics of Ephb2-KO cells were interrogated using phenotypic and functional assays. Ephb2-KO SSCs exhibited reduced proliferation compared to wild-type cells, while apoptosis was unaffected. Therefore, we examined whether Ephb2 loss correlates with activity of canonical pathways involved in stem cell self-renewal and proliferation. Ephb2-KO cells had reduced ERK MAPK signaling. Using a lentiviral transgene, Ephb2 expression was rescued in Ephb2-KO cells, which partially restored signaling and proliferation. Transplantation analysis revealed that Ephb2-KO SSCs cultures formed significantly fewer colonies than WT, indicating a role for Ephb2 in preserving stem cell activity of cultured cells. Transcriptome analysis of wild-type and Ephb2-KO SSCs identified Dppa4 and Bnc1 as differentially expressed, Ephb2-dependent genes that are potentially involved in stem cell function. These data uncover for the first time a crucial role for Ephb2 signaling in cultured SSCs. Summary sentence The tyrosine kinase receptor Ephb2 is required for normal proliferation and stem cell activity of adult mouse spermatogonia in long-term culture.
Plexiform fibrohistiocytic tumor on the chest of a 5‐year‐old child and review of the literature

Plexiform fibrohistiocytic tumor (PFT) is a rare neoplasm of mesenchymal origin that can be identified by its propensity for children and adolescents combined with a characteristic histologic arrangement of histiocytes and osteoclast‐like giant cells whorled within tumor islands. A 5‐year‐old female presented with a raised, intermittently tender, and slowly enlarging tumor on her chest, which was histologically confirmed to be a PFT. We present this case along with a comprehensive review of PFT cases reported in the literature to describe the demographic, histologic, and rarely metastatic behavior of this entity. It is important to include PFT on the differential diagnosis of an enlarging tumor in the pediatric population.
Effect of ANGPTL7 on Proliferation and Differentiation of MC3T3-E1 Cells

Background Angiopoietin-like proteins (ANGPTL) are a family of secretory glycoproteins that are involved in many pathophysiological processes. ANGPTL7 is a newly-discovered member of the ANGPTL family and plays a role in corneal morphogenesis, angiogenesis, glaucoma, and cancer. To date, whether ANGPTL7 is involved in osteoporosis is unknown. Therefore, to discover the effects of ANGPTL7 on osteoporosis, we explored the expression of ANGPTL7 in preosteoblasts and assessed the mechanism underlying its effects on proliferation and differentiation abilities of preosteoblasts. Material/Methods Mouse MC3T3-E1 cells were cultured in osteogenic medium for osteogenic differentiation. The expression levels of ANGPTL7 were detected by RT-qPCR and Western blot assays. Moreover, the overexpressed plasmid of ANGPTL7 pMSCV-ANGPTL7 was transfected into MC3T3-E1 cells. CCK-8 was used to evaluate cell proliferation. ALP activity detection and alizarin red staining were performed to measure the effect of ANGPTL7 on osteogenic differentiation. The expression levels bone morphogenetic proteins (BMPs) and osteogenic markers ALP, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen I (Col I) were analyzed by Western blot. Results When MC3T3-E1 cells were exposed to osteogenic medium, there was a significant increase in ANGPTL7, and overexpression of ANGPTL7 markedly promoted cell proliferation, ALP activity, and mineralization. Moreover, ANGPTL7 upregulated the levels of BMPs, especially BMP2/7, and the osteogenic markers ALP, Runx2, OCN, and Col I. Conclusions The results suggest that by regulating the expression of BMPs, ANGPTL7 directly promotes proliferation, differentiation, and mineralization of osteoblasts.
Comparative study of the neural differentiation capacity of mesenchymal stromal cells from different tissue sources: An approach for their use in neural regeneration therapies

Mesenchymal stem cells (MSCs) can trans/differentiate to neural precursors and/or mature neurons and promote neuroprotection and neurogenesis. The above could greatly benefit neurodegenerative disorders as well as in the treatment of post-traumatic and hereditary diseases of the central nervous system (CNS). In order to attain an ideal source of adult MSCs for the treatment of CNS diseases, adipose tissue, bone marrow, skin and umbilical cord derived MSCs were isolated and studied to explore differences with regard to neural differentiation capacity. In this study, we demonstrated that MSCs from several tissues can differentiate into neuron-like cells and differentially express progenitors and mature neural markers. Adipose tissue MSCs exhibited significantly higher expression of neural markers and had a faster proliferation rate. Our results suggest that adipose tissue MSCs are the best candidates for the use in neurological diseases.
Problematic Internet Use and Smoking among Chinese Junior Secondary Students: The Mediating Role of Depressive Symptomatology and Family Support

Background: Internet use is significant public health issue and can be a risk factor for other addictive behaviors, such as smoking. The present study examined the association between problematic Internet use (PIU) (i.e., Internet addiction (IA) and social networking addiction (SNA)) and smoking, and the mediating role of depressive symptomatology and family support played in such associations. Methods: A cross-sectional study was conducted among 5182 junior secondary students (grade 7 and 8) recruited from nine schools using stratified sampling. Results: A total of 3.6% of students had smoked in the past month, and 6.4% of students were identified as IA cases. Adjusted for significant background variables, PIU (ORa = 2.07, 95% CI = 1.48, 2.90 for IA, ORa = 1.26, 95% CI = 1.09, 1.47 for SNA), and probable depression (ORa = 1.33, 95% CI = 1.05, 1.69) were significant risk factors, while family support (ORa = 0.85, 95% CI = 0.77, 0.94) was a significant protective factor of smoking. The mediation effects of lower family support and probable depression on the association between score on IA scale and smoking, and the mediation effect of lower family support on the association between score on SNA scale and smoking were significant, while the mediation effect of probable depression on the association between score on SNA scale and smoking was marginally significant. Conclusions: PIU contributed to an increased risk of smoking through depressive symptomatology and decreasing family support among junior school students. Interventions to reduce smoking are warranted; they should seek to reduce problematic Internet use and depressive symptomatology, and promote family support.