bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiles of Internet Use and Health in Adolescence: A Person-Oriented Approach
Authors: Lahti Henri , Lyyra Nelli , Hietajärvi Lauri , Villberg Jari , Paakkari Leena
Published: June 2021

(1) Background: Internet use has become an integral part of adolescents’ daily lives. It is important to understand how adolescents use the internet, and how this use is associated with demographic factors and health from a person-oriented perspective. (2) Methods: The study applied the Finnish nationally representative HBSC data (persons aged 11, 13, and 15, n = 3408), descriptive observation, latent class analysis, and multinomial logistic regression analysis. (3) Results: Entertainment activities (listening to music) and socially oriented activities (liking posts, talking online) were the most prevalent among adolescents, but gender differences emerged. Five different internet user profiles were identified (encompassing interest-driven, friendship-driven, abstinent, irregular, and excessive users). Interest-driven users participated in interest- and media-oriented activities. Adolescents in the interest-driven user group were more likely to be boys and participants with low academic achievement, high parental monitoring, and high problematic social media use. Friendship-driven users participated in socially oriented activities. Adolescents in the friendship-driven user group were more likely to be girls and participants aged 13 or 15, with high peer and family support. Abstinent users participated only in entertainment, while irregular users showed no particularly high involvement in any internet activity. Adolescents in the abstinent and irregular user groups were likely to be boys and participants aged 11 with high family support. Excessive users had high involvement in internet activities overall. Adolescents in the excessive user group were more likely to be participants with high problematic social media use and were most likely to feel low and tired on school mornings. (4) Conclusion: The study confirmed the prevalence of internet use. It identified five internet user profiles and differences between user profiles regarding individual and social factors and health outcomes.
Early Left Ventricular Diastolic Dysfunction, Reduced Baroreflex Sensitivity, and Cardiac Autonomic Imbalance in Anabolic–Androgenic Steroid Users
Authors: Kouidi Evangelia Joseph , Kaltsatou Antonia , Anifanti Maria Apostolos , Deligiannis Asterios Pantazis
Published: June 2021

The effects of androgen anabolic steroids (AAS) use on athletes’ cardiac autonomic activity in terms of baroreflex sensitivity (BRS), and heart rate variability (HRV) have not yet been adequately studied. Furthermore, there is no information to describe the possible relationship between the structural and functional cardiac remodeling and the cardiac autonomic nervous system changes caused by AAS abuse. Thus, we aimed to study the effects of long-term AAS abuse on cardiac autonomic efficacy and cardiac adaptations in strength-trained athletes. In total, 80 strength-trained athletes (weightlifters and bodybuilders) participated in the study. Notably, 40 of them using AAS according to their state formed group A, 40 nonuser strength-trained athletes comprised group B, and 40 healthy nonathletes (group C) were used as controls. All subjects underwent a head-up tilt test using the 30 min protocol to evaluate the baroreflex sensitivity and short HRV modulation. Furthermore, all athletes undertook standard echocardiography, a cardiac tissue Doppler imaging (TDI) study, and a maximal spiroergometric test on a treadmill to estimate their maximum oxygen consumption (VO2max). The tilt test results showed that group A presented a significantly lower BRS and baroreflex effectiveness index than group B by 13.8% and 10.7%, respectively (p < 0.05). Regarding short-term HRV analysis, a significant increase was observed in sympathetic activity in AAS users. Moreover, athletes of group A showed increased left ventricular (LV) mass index (LVMI) by 8.9% (p < 0.05), compared to group B. However, no difference was found in LV ejection fraction between the groups. TDI measurements indicated that AAS users had decreased septal and lateral peak E’ by 38.0% (p < 0.05) and 32.1% (p < 0.05), respectively, and increased E/E’ by 32.0% (p < 0.05), compared to group B. This LV diastolic function alteration was correlated with the year of AAS abuse. A significant correlation was established between BRS depression and LV diastolic impairment in AAS users. Cardiopulmonary test results showed that AAS users had significantly higher time to exhaustion by 11.0 % (p < 0.05) and VO2max by 15.1% (p < 0.05), compared to controls. A significant correlation was found between VO2max and LVMI in AAS users. The results of the present study indicated that long-term AAS use in strength-trained athletes led to altered cardiovascular autonomic modulations, which were associated with indices of early LV diastolic dysfunction.
The Olfactory System as Marker of Neurodegeneration in Aging, Neurological and Neuropsychiatric Disorders
Authors: Bhatia-Dey Naina , Heinbockel Thomas
Published: June 2021

Research studies that focus on understanding the onset of neurodegenerative pathology and therapeutic interventions to inhibit its causative factors, have shown a crucial role of olfactory bulb neurons as they transmit and propagate nerve impulses to higher cortical and limbic structures. In rodent models, removal of the olfactory bulb results in pathology of the frontal cortex that shows striking similarity with frontal cortex features of patients diagnosed with neurodegenerative disorders. Widely different approaches involving behavioral symptom analysis, histopathological and molecular alterations, genetic and environmental influences, along with age-related alterations in cellular pathways, indicate a strong correlation of olfactory dysfunction and neurodegeneration. Indeed, declining olfactory acuity and olfactory deficits emerge either as the very first symptoms or as prodromal symptoms of progressing neurodegeneration of classical conditions. Olfactory dysfunction has been associated with most neurodegenerative, neuropsychiatric, and communication disorders. Evidence revealing the dual molecular function of the olfactory receptor neurons at dendritic and axonal ends indicates the significance of olfactory processing pathways that come under environmental pressure right from the onset. Here, we review findings that olfactory bulb neuronal processing serves as a marker of neuropsychiatric and neurodegenerative disorders.
Perceptions and Experiences of the COVID-19 Pandemic amongst Frontline Nurses and Their Relatives in France in Six Paradoxes: A Qualitative Study
Authors: Chandler-Jeanville Stephanie , Nohra Rita Georges , Loizeau Valerie , Lartigue-Malgouyres Corinne , Zintchem Roger , Naudin David , Rothan-Tondeur Monique
Published: June 2021

Due to their frontline position to fight the coronavirus disease 2019 (COVID-19), the professional and personal life of nurses was severely disrupted. To understand and describe their lived experiences and perceptions during the pandemic’s first wave in France, we interviewed 49 nurses, including 16 nursing students, and 48 of their family members from June to July 2020. Using a purposeful sampling, the semi-structured interviews were scripted according to Abric’s method with probing questions. The interview analysis led to the identification of six paradoxical perceptions concerning the pandemic’s consequences: the Silence Paradox, the Hero Paradox, the Workforce Paradox, the Learning Paradox, the Symbolic Exchange Paradox, and the Uncertainty Paradox. However, despite different experiences, the nurses perceived their frontline position both as a burden jeopardizing their safety and well-being and as a spotlight of nurses’ tough working conditions. Indeed, because they were in the frontline position, nurses and nursing students were psychologically vulnerable, even more so when they felt alone and inadequately protected. Besides, their families were vulnerable too, as they were also exposed to the consequences of the nurses’ frontline engagement. Thus, to preserve their safety and well-being, institutions should also provide them with better organizational support and inclusive leadership, without neglecting their families.
Comparative Evaluation of Esthetic and Structural Aspects in Class II Functional Therapy. A Case–Control Retrospective Study
Authors: Galluccio Gabriella , Guarnieri Rosanna , Jamshir Diana , Impellizzeri Alessandra , Ierardo Gaetano , Barbato Ersilia
Published: June 2021

Background: To compare the skeletal, dental, and esthetic changes produced by three functional devices, Fränkel-2 appliance (FR-2), Twin Block (TB), and Occlus-o-Guide® (O-o-G®), for the treatment of Class II malocclusion. Methods: Sixty-five patients with Class II Division 1 malocclusion were divided into three groups and were analyzed through cephalometric analysis of skeletal, dental, and esthetic variables before and after treatment. The first group of 23 patients (F: 9; M: 14; mean age: 10.3 ± 1.08 years) was treated with FR-2, the second group of 18 patients (F: 8; M: 10; mean age 10.7 ± 1.05 years) was treated with TB, the third group (F: 11; M: 13; mean age: 9.05 ± 0.39 years) of 24 patients was treated with O-o-G®. The structural effects of the three devices were compared with a control group generated by the growth variations reported in the cephalometric atlas of Bhatia and Leighton. Esthetic analysis was performed comparing the results of the patients treated with a control group of 20 subjects with mandibular retrognathia and Class II Division 1 malocclusion, not subjected to therapy. Results: The three devices resulted in a significant increase in mandibular length, with higher results obtained for FR-2 and TB. A statistically significant increase in the IMPA angle was found for the O-o-G® group, and a notable reduction of both overjet and overbite was detected in all three groups of treated patients. The esthetic evaluation showed overall more significant results in the TB group, especially with regard to the reduction of facial convexity. The retrusion of the upper lip was on average more significant in the O-o-G® group, followed by that in the TB. Conclusions: All three devices have proven to be effective overall in resolving skeletal changes and improving facial esthetics.
Revising Endosomal Trafficking under Insulin Receptor Activation
Authors: Iraburu Maria J. , Garner Tommy , Montiel-Duarte Cristina
Published: June 2021

The endocytosis of ligand-bound receptors and their eventual recycling to the plasma membrane (PM) are processes that have an influence on signalling activity and therefore on many cell functions, including migration and proliferation. Like other tyrosine kinase receptors (TKR), the insulin receptor (INSR) has been shown to be endocytosed by clathrin-dependent and -independent mechanisms. Once at the early endosome (EE), the sorting of the receptor, either to the late endosome (LE) for degradation or back to the PM through slow or fast recycling pathways, will determine the intensity and duration of insulin effects. Both the endocytic and the endosomic pathways are regulated by many proteins, the Arf and Rab families of small GTPases being some of the most relevant. Here, we argue for a specific role for the slow recycling route, whilst we review the main molecular mechanisms involved in INSR endocytosis, sorting and recycling, as well as their possible role in cell functions.
The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta
Authors: Walsh Scott W. , Strauss Jerome F.
Published: June 2021

The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started <16 weeks of gestation and at doses >100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin’s effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.
C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age
Authors: Zanella Isabella , Zacchi Eliana , Piva Simone , Filosto Massimiliano , Beligni Giada , Alaverdian Diana , Amitrano Sara , Fava Francesca , Baldassarri Margherita , Frullanti Elisa , Meloni Ilaria , Renieri Alessandra ,   GEN-COVID Multicenter Study,   GEVACOBA Study Group, Castelli Francesco , Quiros-Roldan Eugenia
Published: June 2021

A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04–5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.
Integrated Analysis of miR-430 on Steroidogenesis-Related Gene Expression of Larval Rice Field Eel Monopterus albus
Authors: Zhang Lihan , Yang Qiushi , Xu Weitong , Wu Zhaojun , Li Dapeng
Published: June 2021

The present study aims to reveal the mechanism by which miR-430s regulate steroidogenesis in larval rice field eel Monopterus albus. To this end, M. albus embryos were respectively microinjected with miRNA-overexpressing mimics (agomir430a, agomir430b, and agomir430c) or miRNA-knockdown inhibitors (antagomir430a, antagomir430b, and antagomir430c). Transcriptome profiling of the larvae indicated that a total of more than 149 differentially expressed genes (DEGs) were identified among the eight treatments. Specifically, DEGs related to steroidogenesis, the GnRH signaling pathway, the erbB signaling pathway, the Wnt signaling pathway, and other pathways were characterized in the transcriptome. We found that steroidogenesis-related genes (hydroxysteroid 17-beta dehydrogenase 3 (17β-hsdb3), hydroxysteroid 17-beta dehydrogenase 7 (17β-hsdb7), hydroxysteroid 17-beta dehydrogenase 12 (17β-hsdb12), and cytochrome P450 family 19 subfamily a (cyp19a1b)) were significantly downregulated in miR-430 knockdown groups. The differential expressions of miR-430 in three gonads indicated different roles of three miR-430 (a, b, and c) isoforms in regulating steroidogenesis and sex differentiation. Mutation of the miR-430 sites reversed the downregulation of cytochrome P450 family 17 (cyp17), cyp19a1b, and forkhead box L2 (foxl2) reporter activities by miR-430, indicating that miR-430 directly interacted with cyp17, cyp19a1b, and foxl2 genes to inhibit their expressions. Combining these findings, we concluded that miR-430 regulated the steroidogenesis and the biosynthesis of steroid hormones by targeting cyp19a1b in larval M. albus. Our results provide a novel insight into steroidogenesis at the early stage of fish at the molecular level.
Does the SARS-CoV-2 Spike Protein Receptor Binding Domain Interact Effectively with the DPP4 (CD26) Receptor? A Molecular Docking Study
Authors: Cameron Kirsten , Rozano Lina , Falasca Marco , Mancera Ricardo L.
Published: June 2021

ACE2 has been established as the main receptor for SARS-CoV-2. Since other human coronaviruses are known to use co-receptors for viral cell entry, it has been suggested that DPP4 (CD26) could be a potential additional binding target or co-receptor, supported by early molecular docking simulation studies. However, recent biophysical studies have shown this interaction to be very weak. We have conducted detailed molecular docking simulations to predict the potential binding interactions between the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 and DPP4 and compare them with the interactions observed in the experimentally determined structure of the complex of MERS-CoV with DPP4. Whilst the overall binding mode of the RBD of SARS-CoV-2 to DPP4 is predicted to be similar to that observed in the MERS-CoV-DPP4 complex, including a number of equivalent interactions, important differences in the amino acid sequences of SARS-CoV-2 and MERS-CoV result in substantially weakened interactions with DPP4. This is shown to arise from differences in the predicted proximity, nature and secondary structure at the binding interface on the RBD of SARS-CoV-2. These findings do not support DPP4 being a significant receptor for SARS-CoV-2.
Cytosolic 5′-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway
Authors: Pesi Rossana , Allegrini Simone , Garcia-Gil Mercedes , Piazza Lucia , Moschini Roberta , Jordheim Lars Petter , Camici Marcella , Tozzi Maria Grazia
Published: June 2021

Cytosolic 5′-nucleotidase II (cN-II) is an allosteric catabolic enzyme that hydrolyzes IMP, GMP, and AMP. The enzyme can assume at least two different structures, being the more active conformation stabilized by ATP and the less active by inorganic phosphate. Therefore, the variation in ATP concentration can control both structure and activity of cN-II. In this paper, using a capillary electrophoresis technique, we demonstrated that a partial silencing of cN-II in a pulmonary carcinoma cell line (NCI-H292) is accompanied by a decrease in adenylate pool, without affecting the energy charge. We also found that cN-II silencing decreased proliferation and increased oxidative metabolism, as indicated by the decreased production of lactate. These effects, as demonstrated by Western blotting, appear to be mediated by both p53 and AMP-activated protein kinase, as most of them are prevented by pifithrin-α, a known p53 inhibitor. These results are in line with our previous observations of a shift towards a more oxidative and less proliferative phenotype of tumoral cells with a low expression of cN-II, thus supporting the search for specific inhibitors of this enzyme as a therapeutic tool for the treatment of tumors.
Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in Prostate Cancer Cells
Authors: Bevacqua Emilia , Curcio Manuela , Saletta Federica , Vittorio Orazio , Cirillo Giuseppe , Tucci Paola
Published: June 2021

Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC50 reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.
Saliva Proteomics as Fluid Signature of Inflammatory and Immune-Mediated Skin Diseases
Authors: Campanati Anna , Martina Emanuela , Diotallevi Federico , Radi Giulia , Marani Andrea , Sartini Davide , Emanuelli Monica , Kontochristopoulos George , Rigopoulos Dimitris , Gregoriou Stamatis , Offidani Annamaria
Published: June 2021

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren’s syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.
Transamidation Down-Regulates Intestinal Immunity of Recombinant α-Gliadin in HLA-DQ8 Transgenic Mice
Authors: Rossi Stefano , Giordano Deborah , Mazzeo Maria Fiorella , Maurano Francesco , Luongo Diomira , Facchiano Angelo , Siciliano Rosa Anna , Rossi Mauro
Published: June 2021

Enzymatic transamidation of gliadins by microbial transglutaminase (mTG) inhibits interferon-γ (IFN-γ) secretion by intestinal T cell lines in patients with celiac disease (CD). To gain insight into the cellular mechanisms underlying the down-regulatory effects of transamidation, we tested a single recombinant α-gliadin (r-gliadin) harbouring two immunodominant peptides, p13 (aa. 120–139) and p23 (aa. 220–239), in HLA-DQ8 transgenic mice, a model of gluten sensitivity. Mice were intranasally immunised with r-gliadin or r-gliadin transamidated by mTG (K-r-gliadin) along with cholera toxin, and the response of mesenteric lymph node cells was analysed by cytokine multiplex assay. An in vitro challenge with r-gliadin was characterised by secretion of specific cytokines featuring both innate immunity and the Th1/Th2/Th17 pattern of the adaptive response. Notably, transamidation specifically down-regulated the Th1 response. Structural studies performed on K-r-gliadin confirmed that specific glutamine residues in p13 and p23, previously found to be deamidated by tissue transglutaminase, were also transamidated by mTG. In silico analysis, simulating p13 and p23 peptide binding to HLA-DQ8 showed that these glutamines, in the form of glutamate, could interact by means of salt bridges with peculiar amino acids of the alpha chain of HLA-DQ8, suggesting that their transamidation may influence the HLA-restricted recognition of these peptides. Thus, the structural findings provided a rationale to explain the down-regulation of the r-gliadin-specific Th1 response following transamidation.
The Role of DAMPS in Burns and Hemorrhagic Shock Immune Response: Pathophysiology and Clinical Issues. Review
Authors: Pantalone Desirè , Bergamini Carlo , Martellucci Jacopo , Alemanno Giovanni , Bruscino Alessandro , Maltinti Gherardo , Sheiterle Maximilian , Viligiardi Riccardo , Panconesi Roberto , Guagni Tommaso , Prosperi Paolo
Published: June 2021

Severe or major burns induce a pathophysiological, immune, and inflammatory response that can persist for a long time and affect morbidity and mortality. Severe burns are followed by a “hypermetabolic response”, an inflammatory process that can be extensive and become uncontrolled, leading to a generalized catabolic state and delayed healing. Catabolism causes the upregulation of inflammatory cells and innate immune markers in various organs, which may lead to multiorgan failure and death. Burns activate immune cells and cytokine production regulated by damage-associated molecular patterns (DAMPs). Trauma has similar injury-related immune responses, whereby DAMPs are massively released in musculoskeletal injuries and elicit widespread systemic inflammation. Hemorrhagic shock is the main cause of death in trauma. It is hypovolemic, and the consequence of volume loss and the speed of blood loss manifest immediately after injury. In burns, the shock becomes evident within the first 24 h and is hypovolemic-distributive due to the severely compromised regulation of tissue perfusion and oxygen delivery caused by capillary leakage, whereby fluids shift from the intravascular to the interstitial space. In this review, we compare the pathophysiological responses to burns and trauma including their associated clinical patterns.
Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer’s Disease
Authors: Jalali David , Guevarra Justine Anne , Martinez Luz , Hung Lily , Vonhoff Fernando J
Published: June 2021

Studies using animal models have shed light into the molecular and cellular basis for the neuropathology observed in patients with Alzheimer’s disease (AD). In particular, the role of the amyloid precursor protein (APP) plays a crucial role in the formation of senile plaques and aging-dependent degeneration. Here, we focus our review on recent findings using the Drosophila AD model to expand our understanding of APP molecular function and interactions, including insights gained from the fly homolog APP-like (APPL). Finally, as there is still no cure for AD, we review some approaches that have shown promising results in ameliorating AD-associated phenotypes, with special attention on the use of nutraceuticals and their molecular effects, as well as interactions with the gut microbiome. Overall, the phenomena described here are of fundamental significance for understanding network development and degeneration. Given the highly conserved nature of fundamental signaling pathways, the insight gained from animal models such as Drosophila melanogaster will likely advance the understanding of the mammalian brain, and thus be relevant to human health.
Bioengineered Ferritin Nanocarriers for Cancer Therapy
Authors: Sun Xuanrong , Hong Yulu , Gong Yubei , Zheng Shanshan , Xie Dehui
Published: June 2021

Ferritin naturally exists in most organisms and can specifically recognize the transferrin 1 receptor (TfR1), which is generally highly expressed on various types of tumor cells. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. Recent studies, further establish ferritin as a multifunctional nanocarrier for targeted cancer chemotherapy and phototherapy. In this review, we introduce the favorable characteristics of ferritin drug carriers, the specific targeted surface modification and a multifunctional nanocarriers combined chemotherapy with phototherapy for tumor treatment. Taken together, ferritin is a potential ideal base of engineered nanoparticles for tumor therapy and still needs to explore more on its way.
Comparative Transcriptome Analysis Reveals Regulatory Networks during the Maize Ear Shank Elongation Process
Authors: Xiong Cai-Yun , Gong Qing-You , Pei Hu , Liao Chang-Jian , Yang Rui-Chun , Li Gao-Ke , Huang Jun
Published: June 2021

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.
Bionic Design and 3D Printing of Continuous Carbon Fiber-Reinforced Polylactic Acid Composite with Barbicel Structure of Eagle-Owl Feather
Authors: Liang Yunhong , Liu Chang , Zhao Qian , Lin Zhaohua , Han Zhiwu , Ren Luquan
Published: June 2021

Inspired by eagle-owl feather with characteristics of light weight and high strength, the bionic continuous carbon fiber-reinforced polylactic acid composite with barbicel structure was successfully 3D printed. Under the action of external load, angles between barbicels and rachis structure of eagle-owl feather decreased, which consumed a part of energy and built structure base of bionic feather structure model with a certain arrangement angle of continuous carbon fiber. Variation of bionic structure model design parameters significantly affected the mechanical properties of the 3D printing bionic composites. The relatively low continuous carbon fiber content on tensile force direction restricted enhancement of tensile strength of bionic composite. However, attributed to different angle arrangement of continuous carbon fiber, the propagation of cracks in bionic composite was hindered, exhibiting high impact resistance. The effective and feasible bionic feather design and 3D printing of continuous carbon fiber-reinforced polylactic acid composite extended the corresponding application in the areas with high impact loads.
Self-Template Synthesis of Nitrogen-Doped Hollow Carbon Nanospheres with Rational Mesoporosity for Efficient Supercapacitors
Authors: Zhao Xiang , Zhang Mu , Pan Wei , Yang Rui , Sun Xudong
Published: June 2021

Rational design and economic fabrication are essential to develop carbonic electrode materials with optimized porosity for high-performance supercapacitors. Herein, nitrogen-doped hollow carbon nanospheres (NHCSs) derived from resorcinol and formaldehyde resin are successfully prepared via a self-template strategy. The porosity and heteroatoms in the carbon shell can be adjusted by purposefully introducing various dosages of ammonium ferric citrate (AFC). Under the optimum AFC dosage (30 mg), the as-prepared NHCS-30 possesses hierarchical architecture, high specific surface area up to 1987 m2·g−1, an ultrahigh mesopore proportion of 98%, and moderate contents of heteroatoms, and these features endow it with a high specific capacitance of 206.5 F·g−1 at 0.2 A·g−1, with a good rate capability of 125 F·g−1 at 20 A·g−1 as well as outstanding electrochemical stability after 5000 cycles in a 6 M KOH electrolyte. Furthermore, the assembled NHCS-30 based symmetric supercapacitor delivers an energy density of 14.1 W·h·kg−1 at a power density of 200 W·kg−1 in a 6 M KOH electrolyte. This work provides not only an appealing model to study the effect of structural and component change on capacitance, but also general guidance to expand functionality electrode materials by the self-template method.
Casein/Apricot Filler in the Production of Flame-Retardant Polyurethane Composites
Authors: Członka Sylwia , Kairytė Agnė , Miedzińska Karolina , Strąkowska Anna
Published: June 2021

Polyurethane (PUR) composites reinforced with 1, 2, and 5 wt.% of apricot filler modified with casein were synthesized in the following study. The impact of 1, 2, and 5 wt.% of casein/apricot filler on the cellular structure and physico-mechanical performances of reinforced PUR composites were determined. It was found that the incorporation of 1 and 2 wt.% of casein/apricot filler resulted in the production of PUR composites with improved selected physical, thermal, and mechanical properties, while the addition of 5 wt.% of casein/apricot filler led to some deterioration of their physico-mechanical performance. The best results were obtained for PUR composites reinforced with 2 wt.% of casein/apricot filler. Those composites were characterized by a uniform structure and a high content of closed cells. Compared with the reference foam, the incorporation of 2 wt.% of casein/apricot filler resulted in improvement in compressive strength, flexural strength, impact strength, and dynamic mechanical properties—such as glass transition temperature and storage modulus. Most importantly, PUR composites showed better fire resistance and thermal stability due to the good thermal performance of casein. The main aim of this article is to determine the influence of the natural combination of the apricot filler and casein on the mechanical properties and flammability of the obtained composites.
The Influence of Different Length Aluminum Foam Filling on Mechanical Behavior of a Square Thin-Walled Column
Authors: Rogala Michał , Ferdynus Mirosław , Gawdzińska Katarzyna , Kochmański Paweł
Published: June 2021

The demand for lightweight, strong structural profiles is currently high in the transport industry, mechanical engineering, and construction. Therefore, it is important to evaluate their properties, especially mechanical properties. The main objective of this paper is to determine energy absorption coefficients and evaluate the crush resistance of thin-walled aluminum profiles using numerical simulation and empirical verification. This paper presents the compression results of testing of thin-walled aluminum profiles filled with a porous material (cast aluminum foam). The numerical analysis was conducted using the software Abaqus/CAE. Aluminum material data were obtained from a static tensile test performed on a Shimadzu machine. The experiment was performed on an Instron CEAST 9450HES dynamic hammer. Profiles with three shapes of crush initiators filled with aluminum foam measuring 40 mm–200 mm in 20 mm increments were numerically tested. A sample with a concave initiator filled with foams of 40 mm, 60 mm, 80 mm, and 120 mm in length was used to verify the numerical analyses. Energy absorption coefficients were determined from the analyses. The results of both analyses were tabulated to show the percentage differences. The study showed an increase in the Crush Load Efficiency (CLE) index by up to 33% for samples with the same crush initiator. In addition, it was noted that the use of porous fill does not increase the value of initiating Peak Crushing Force (PCF), which indicates the generation of much smaller overloads dangerous for vehicle passengers.
On the Condition of Independence of Linear Forms with a Random Number of Summands
Authors: Kagan Abram M. , Klebanov Lev B.
Published: June 2021

The property of independence of two random forms with a non-degenerate random number of summands contradicts the Gaussianity of the summands.
Comparative Study on Seed Characteristics, Antioxidant Activity, and Total Phenolic and Flavonoid Contents in Accessions of Sorghum bicolor (L.) Moench
Authors: Ghimire Bimal-Kumar , Seo Ji-Won , Yu Chang-Yeon , Kim Seung-Hyun , Chung Ill-Min
Published: June 2021

Sorghum is a major cereal food worldwide, and is considered a potential source of minerals and bioactive compounds. Its wide adaptive range may cause variations in its agronomic traits, antioxidant properties, and phytochemical content. This extensive study investigated variations in seed characteristics, antioxidant properties, and total phenolic (TPC) and flavonoid contents (TFC) of sorghum collected from different ecological regions of 15 countries. The antioxidant potential of the seed extracts of various sorghum accessions was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis 3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging assays. Significant variations in TPC were observed among the sorghum accessions. All 78 sorghum accessions used in this study exhibited significant variations in TFC, with the lowest and highest amount observed in accessions C465 and J542, respectively. DPPH scavenging potential of the seed extracts for all the accessions ranged from 11.91 ± 4.83 to 1343.90 ± 81.02 µg mL−1. The ABTS assay results were similar to those of DPPH but showed some differences in the accessions. Pearson’s correlation analysis revealed a wide variation range in the correlation between antioxidant activity and TPC, as well as TFC, among the sorghum accessions. A wide diversity range was also recorded for the seed characteristics (1000-seed weight and seed germination rate). A dendrogram generated from UPGMA clustering, based on seed traits, antioxidant activity, TPC, and TFC was highly dispersed for these accessions. Variations among the accessions may provide useful information regarding the phytoconstituents, antioxidant properties, and phytochemical contents of sorghum and aid in designing breeding programs to obtain sorghum with improved agronomic traits and bioactive properties.
Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects
Authors: d’Abadie Philippe , Hesse Michel , Louppe Amandine , Lhommel Renaud , Walrand Stephan , Jamar Francois
Published: June 2021

Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres’ properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.
High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS
Authors: Wang Shaoyun , Sun Xiaozhu , An Shuo , Sang Fang , Zhao Yunli , Yu Zhiguo
Published: June 2021

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.
Chlorine-Functional Silsesquioxanes (POSS-Cl) as Effective Flame Retardants and Reinforcing Additives for Rigid Polyurethane Foams
Authors: Strąkowska Anna , Członka Sylwia , Miedzińska Karolina , Strzelec Krzysztof
Published: June 2021

The subject of the research was the production of silsesquioxane modified rigid polyurethane (PUR) foams (POSS-Cl) with chlorine functional groups (chlorobenzyl, chloropropyl, chlorobenzylethyl) characterized by reduced flammability. The foams were prepared in a one-step additive polymerization reaction of isocyanates with polyols, and the POSS modifier was added to the reaction system in an amount of 2 wt.% polyol. The influence of POSS was analyzed by performing a series of tests, such as determination of the kinetics of foam growth, determination of apparent density, and structure analysis. Compressive strength, three-point bending strength, hardness, and shape stability at reduced and elevated temperatures were tested, and the hydrophobicity of the surface was determined. The most important measurement was the determination of the thermal stability (TGA) and the flammability of the modified systems using a cone calorimeter. The obtained results, after comparing with the results for unmodified foam, showed a large influence of POSS modifiers on the functional properties, especially thermal and fire-retardant, of the obtained PUR-POSS-Cl systems.
Improvement of Temperature and Optical Power of an LED by Using Microfluidic Circulating System of Graphene Solution
Authors: Chung Yung-Chiang , Chung Han-Hsuan , Lin Shih-Hao
Published: June 2021

Electric devices have evolved to become smaller, more multifunctional, and increasingly integrated. When the total volume of a device is reduced, insufficient heat dissipation may result in device failure. A microfluidic channel with a graphene solution may replace solid conductors for simultaneously supplying energy and dissipating heat in a light emitting diode (LED). In this study, an automated recycling system using a graphene solution was designed that reduces the necessity of manual operation. The optical power and temperature of an LED using this system was measured for an extended period and compared with the performance of a solid conductor. The temperature difference of the LED bottom using the solid and liquid conductors reached 25 °C. The optical power of the LED using the liquid conductor was higher than that of the solid conductor after 120 min of LED operation. When the flow rate was increased, the temperature difference of the LED bottom between initial and 480 min was lower, and the optical power of the LED was higher. This result was attributable to the higher temperature of the LED with the solid conductor. Moreover, the optical/electric power transfer rate of the liquid conductor was higher than that of the solid conductor after 120 min of LED operation, and the difference increased over time.
Validation of Architecture Effectiveness for the Continuous Monitoring of File Integrity Stored in the Cloud Using Blockchain and Smart Contracts
Authors: Pinheiro Alexandre , Canedo Edna Dias , Albuquerque Robson de Oliveira , de Sousa Júnior Rafael Timóteo
Published: June 2021

The management practicality and economy offered by the various technological solutions based on cloud computing have attracted many organizations, which have chosen to migrate services to the cloud, despite the numerous challenges arising from this migration. Cloud storage services are emerging as a relevant solution to meet the legal requirements of maintaining custody of electronic documents for long periods. However, the possibility of losses and the consequent financial damage require the permanent monitoring of this information. In a previous work named “Monitoring File Integrity Using Blockchain and Smart Contracts”, the authors proposed an architecture based on blockchain, smart contract, and computational trust technologies that allows the periodic monitoring of the integrity of files stored in the cloud. However, the experiments carried out in the initial studies that validated the architecture included only small- and medium-sized files. As such, this paper presents a validation of the architecture to determine its effectiveness and efficiency when storing large files for long periods. The article provides an improved and detailed description of the proposed processes, followed by a security analysis of the architecture. The results of both the validation experiments and the implemented defense mechanism analysis confirm the security and the efficiency of the architecture in identifying corrupted files, regardless of file size and storage time.