bluuebunny/crossref_metadata_2025 huggingface dataset:
Sap Analysis: A Powerful Tool for Monitoring Plant Nutrition
Authors: Esteves Eduardo , Locatelli Guilherme , Bou Neus Alcon , Ferrarezi Rhuanito Soranz
Published: October 2021

Horticultural crop production is moving towards an era of higher nutrient use efficiency since nutrient deficiencies can reduce plant growth, productivity, and quality, and overfertilization can cause environmental pollution. Rapid nutrient concentration diagnostic is essential to minimize the negative effects of Huanglongbing (HLB) or citrus greening in citrus by providing the required nutrients before deficiency symptoms appear, reducing the impact of the disease on crop production. Sap analysis is an additional tool for fine-tuning nutrient applications in citrus. The main objective of this paper is to review the different methodologies and results obtained with sap analysis, considering its potential application in citrus production. Results from other crops show the pros and cons of using this tool. Substantial research has been conducted on vegetables and greenhouse crops, but few studies are available on perennial species such as citrus. Inconsistency in the extraction and analysis methods and the lack of specific sufficiency ranges for citrus open the path for further studies. Along with soil and leaf analyses, sap analysis is a complementary technique that can improve nutrient use efficiency in citrus production. Moreover, sap analysis has the potential to optimize fertilizer application, minimize environmental impacts and improve sustainability.
Effects of Pollination Interventions, Plant Age and Source on Hormonal Patterns and Fruit Set of Date Palm (Phoenix dactylifera L.)
Authors: Ali-Dinar Hassan , Mohammed Maged , Munir Muhammad
Published: October 2021

Date palm is widely propagated through conventional offshoots. It is also produced through a tissue culture technique due to the limited number of offshoots produced throughout the course of a palm’s life. Being dioecious, it is a cross-pollinated tree that can be naturally or artificially pollinated. Tissue-cultured plants often have abnormal epigenetic or genetic changes that affect specific phenotypic characteristics. The growth of parthenocarpic fruits in date palms is mostly induced by hormonal imbalances in certain tissues. The major hormones in parthenocarpic fruits are auxins (IAA), gibberellins (GA3), and abscisic acid (ABA). Parthenocarpic, or abnormal fruit development, is an undesirable trait for date palm growers since it drastically reduces farm income. The current study was therefore conducted over two seasons to confirm previous observations and included conventional offshoot-derived trees (CO) and tissue culture-derived ones (TC) of the cultivar Barhee. According to the observed ratio of the fruiting abnormalities, two date palm tree ages were selected, i.e., 6 and 13 years. Two pollination interventions were used: pollination of naturally open female spathes (NOP) and pollination of forced open female spathes (FOP). Plant hormones, IAA, GA3, and ABA were identified just before pollination and at specific intervals after pollination for up to 85 days. The ratio of the abnormal fruit set was identified 5 days after pollination. Significant differences were observed in hormonal levels between tree ages as well as between tree propagation sources. Young TC trees (6-year-old) had high abnormal fruit sets compared to CO date palm trees that were the same age. During the early fruit growth and development phases, CO date palms had much higher amounts of IAA and GA3 than TC date palms. However, ABA concentrations were surprisingly higher in the TC trees during the early fruit growth stages, while it immediately decreased after pollination in the CO date palms. The ratio of abnormal fruits was significantly reduced in the 13-year-old TC date palms, and no differences were observed compared to the CO ones. The levels of IAA, GA3, and ABA hormones in both young and old date palms derived through CO or TC followed similar patterns. The critical observations regarding the ABA pattern in the old TC date palms (13-year-old) gradually dropped after pollination, which was identical to the CO ones, whereas it was the opposite in the young 6-year-old TC date palm plants.
Gender Perspective in Research on Interventions in Children with Experiences of Parental Gender-Based Violence: Application of GPIHR Criteria
Authors: Pereira-Román Benjamín , López-Soler Concepción , Alcántara López María Vicenta
Published: October 2021

The aim of this study was to analyse the inclusion of a gender perspective (GP) in scientific production on interventions for a reduction in psychological distress in children who have experienced parental gender-based violence (CEXPGBV). To achieve this, a review of publications was carried out in the Web of Science, EBSCOhost, ProQuest and Cochrane Library databases. A total of 3418 records were found, and 44 items of research selected. For GP analysis, the questionnaire “Gender perspective in health research” (GPIHR) was applied and relationships with the terminology of violence were analysed, as well as the definition of term used, references to violence by men or received by women and the instruments used to assess these. Generally, the assessed studies do not contain a GP, since 70% of the GPIHR items were answered negatively. Likewise, 89% of research used general terms to refer to violence without referring to gender. These results show the importance of considering instruments such as GPIHR in both the planning and development of future research in order to avoid possible gender bias.
Indoor Particulate Matter in Urban Households: Sources, Pathways, Characteristics, Health Effects, and Exposure Mitigation
Authors: Zhang Ling , Ou Changjin , Magana-Arachchi Dhammika , Vithanage Meththika , Vanka Kanth Swaroop , Palanisami Thava , Masakorala Kanaji , Wijesekara Hasintha , Yan Yubo , Bolan Nanthi , Kirkham M. B.
Published: October 2021

Particulate matter (PM) is a complex mixture of solid particles and liquid droplets suspended in the air with varying size, shape, and chemical composition which intensifies significant concern due to severe health effects. Based on the well-established human health effects of outdoor PM, health-based standards for outdoor air have been promoted (e.g., the National Ambient Air Quality Standards formulated by the U.S.). Due to the exchange of indoor and outdoor air, the chemical composition of indoor particulate matter is related to the sources and components of outdoor PM. However, PM in the indoor environment has the potential to exceed outdoor PM levels. Indoor PM includes particles of outdoor origin that drift indoors and particles that originate from indoor activities, which include cooking, fireplaces, smoking, fuel combustion for heating, human activities, and burning incense. Indoor PM can be enriched with inorganic and organic contaminants, including toxic heavy metals and carcinogenic volatile organic compounds. As a potential health hazard, indoor exposure to PM has received increased attention in recent years because people spend most of their time indoors. In addition, as the quantity, quality, and scope of the research have expanded, it is necessary to conduct a systematic review of indoor PM. This review discusses the sources, pathways, characteristics, health effects, and exposure mitigation of indoor PM. Practical solutions and steps to reduce exposure to indoor PM are also discussed.
Association between Dietary Habits and Type 2 Diabetes Mellitus in Yangon, Myanmar: A Case–Control Study
Authors: Ueno Satomi , Aung Myo Nyein , Yuasa Motoyuki , Ishtiaq Ahmad , Khin Ei Thinzar , Latt Tint Swe , Moolphate Saiyud , Sato Setsuko , Tanigawa Takeshi
Published: October 2021

In Myanmar, the escalating prevalence of type 2 diabetes mellitus (T2DM) and impaired glucose tolerance among adults was recently reported, with the highest prevalence in the Yangon Region. The aim of the present study was to identify the risk factors in dietary habits and their relationship with T2DM in urban Myanmar residents. We conducted a case–control study recruiting 300 individuals aged 25–74 years living in the Yangon Region, consisting of 150 newly diagnosed cases attending a diabetes clinic, and 150 controls, who were community residents and free of diabetes. The case group had a significantly higher consumption of noodles, fish, beans, fermented food and pickles, dried food, topping seasonings, and non-dairy milk products than the control group, whereas they had a lower vegetable intake (more than three servings/day) and fruit intake (more than three servings/day) than the control group. Furthermore, the case group exhibited a higher frequency of some dietary behaviors than the control group, such as (1) having meals with family, (2) skipping breakfast, and (3) eating out. The final model showed that topping seasonings (adjusted odds ratio (aOR) 11.23, 95% confidence interval (CI) 3.08–40.90), more than three servings/day of vegetable intake (aOR 0.18, 95% CI 0.05–0.67), and having meals with family (aOR 2.23, 95% CI 1.05–4.71) were associated with diabetes. The study suggests that Myanmar’s characteristic dietary culture of topping their meals with salty seasonings and sauces and eating multiple dishes together as a family are risk factors associated with T2DM. Our findings may contribute recommendations and opportunities for the primary prevention of T2DM in urban Myanmar.
Winning Conditions for the Adoption and Maintenance of Long-Term Healthy Lifestyles According to Physical Activity Students
Authors: Couture-Wilhelmy Laurence , Chaubet Philippe , Gadais Tegwen
Published: October 2021

The literature has not yet well documented the relative elements of the adoption of healthy lifestyle habits (HLHs) over the long term. More especially, researchers are calling to complete the corpus with qualitative or mixed estimates that would allow them to better explain the conditions necessary for the adoption or maintenance of HLHs over the long term. The present study seeks to understand the winning conditions for the adoption and maintenance of HLHs. Semi-structured group interviews were conducted with three groups of university students (two in Bachelor’s degree in physical education (PE) and one in Master’s degree in physical activity science), all in favor with HLHs. The results identify some dominant winning conditions in the adoption and maintenance of HLHs, such as the role of the family environment, the role of diversity and choice in physical activities during youth, the physical and social environment, autonomy and also mental health, which is closely linked with physical health. Results were modelled in the form of an ideal pathway, which traces the impact of winning conditions from childhood to adulthood. The originality of this study stands out, among other things, because of its innovative methodology; therefore, this study opens the door to future qualitative research in the field. Investigating pathways, considering the different phases of development of children and adolescents to identify factors of change and maintenance of HLHs now seems to be an interesting and necessary avenue for research in the field.
Take-Over Intention during Conditionally Automated Driving in China: Current Situation and Influencing Factors
Authors: Feng Zhongxiang , Li Jingyu , Xu Xiaoqin , Guo Amy , Huang Congjun , Jiang Xu
Published: October 2021

Drivers’ take-over intention is important for the design of the automated driving systems and affects the safety of automated driving. This study explored the influence factors on drivers’ take-over intention during conditionally automated driving, examined the correlations among factors through path analysis, and established a take-over intention model. A questionnaire survey was conducted in Hefei, China, and a sample of 277 drivers was obtained. Our study shows that the average take-over intention of those aged under 20 is lower than that of the older age groups. In the positive emotions (PE) scenarios, the take-over intention of aged 31–40 is significantly higher than that of the other age groups. Education and occupation have a significant influence on the take-over intention. The perceived ease of use (PEofU) and perceived usefulness (PU) of automated driving are significantly negatively correlated with drivers’ take-over intention in the road conditions (RC) and climate conditions (CC) scenarios. In addition, through path model analysis, our study shows that trust in the safety of autonomous vehicles (AVs) plays an important role in drivers’ take-over intention. Technology acceptance, risk perception and self-efficacy has indirectly correlated with take-over intention through trust in the safety of AVs. In general, drivers with lower technology acceptance, lower self-efficacy and higher risk perception are less likely to trust automated driving technology and have shown stronger intention to take-over the control of the vehicles.
COVID-Transformer: Interpretable COVID-19 Detection Using Vision Transformer for Healthcare
Authors: Shome Debaditya , Kar T. , Mohanty Sachi , Tiwari Prayag , Muhammad Khan , AlTameem Abdullah , Zhang Yazhou , Saudagar Abdul
Published: October 2021

In the recent pandemic, accurate and rapid testing of patients remained a critical task in the diagnosis and control of COVID-19 disease spread in the healthcare industry. Because of the sudden increase in cases, most countries have faced scarcity and a low rate of testing. Chest X-rays have been shown in the literature to be a potential source of testing for COVID-19 patients, but manually checking X-ray reports is time-consuming and error-prone. Considering these limitations and the advancements in data science, we proposed a Vision Transformer-based deep learning pipeline for COVID-19 detection from chest X-ray-based imaging. Due to the lack of large data sets, we collected data from three open-source data sets of chest X-ray images and aggregated them to form a 30 K image data set, which is the largest publicly available collection of chest X-ray images in this domain to our knowledge. Our proposed transformer model effectively differentiates COVID-19 from normal chest X-rays with an accuracy of 98% along with an AUC score of 99% in the binary classification task. It distinguishes COVID-19, normal, and pneumonia patient’s X-rays with an accuracy of 92% and AUC score of 98% in the Multi-class classification task. For evaluation on our data set, we fine-tuned some of the widely used models in literature, namely, EfficientNetB0, InceptionV3, Resnet50, MobileNetV3, Xception, and DenseNet-121, as baselines. Our proposed transformer model outperformed them in terms of all metrics. In addition, a Grad-CAM based visualization is created which makes our approach interpretable by radiologists and can be used to monitor the progression of the disease in the affected lungs, assisting healthcare.
Twenty-One Reasons for Implementing the Act-Belong-Commit—‘ABCs of Mental Health’ Campaign
Authors: Donovan Robert J. , Koushede Vibeke J. , Drane Catherine F. , Hinrichsen Carsten , Anwar-McHenry Julia , Nielsen Line , Nicholas Amberlee , Meilstrup Charlotte , Santini Ziggi Ivan
Published: October 2021

While there has been increased attention worldwide on mental health promotion over the past two decades, what is lacking in many countries around the globe is practical knowledge of what constitutes a population-wide mental health promotion campaign, and how such a campaign can be implemented. This paper provides such knowledge based on the development, implementation and evaluation of the Act-Belong-Commit campaign, the world’s first comprehensive population-wide public mental health promotion campaign which was launched in 2008 in Western Australia. Given the learnings from the full-scale implementation and evaluation of the campaign in Western Australia and its expansion nationally and internationally, along with the continuing and expanding evidence base for the campaign constructs, we crystallise 21 reasons why jurisdictions who wish to achieve the goals of the WHO and adopt the recommendations of the European framework on mental health and wellbeing should consider adopting or adapting Act-Belong-Commit when considering implementing a public mental health promotion campaign.
Isotemporal Substitution Analysis of Accelerometer-Derived Sedentary Behavior and Physical Activity on Cardiometabolic Health in Korean Adults: A Population-Based Cross-Sectional Study
Authors: Ma Jiameng , Kim Hyunshik , Kim Junghoon
Published: October 2021

Reducing sedentary behavior and increasing physical activity may be important for maintaining good cardiometabolic health. However, many studies have focused on the independent effect of sedentary behavior and physical activity, but it is unclear whether replacing time spent in sedentary behavior with physical activity is beneficial for cardiometabolic health. Therefore, this population-based cross-sectional study aimed to investigate the effect of behavioral transformations between sedentary behavior and level of physical activity on cardiometabolic health in Korean adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2014–2017. The study participants included 2197 adults from the KNHANES. In the partition model, moderate-to-vigorous physical activity (MVPA) was significantly associated with adverse cardiometabolic health, adjusted for potential confounding factors. The odds ratio for adverse cardiometabolic health significantly decreased with the replacement of sedentary behavior and light intensity activity with MVPA in the isotemporal substitution model (p < 0.05). In the models stratified by sex, we observed significant associations between handgrip strength and cardiometabolic health in women (p < 0.001), but not in men. Thus, our findings suggest that replacing sedentary behavior with MVPA may contribute to improved cardiometabolic health.
Perceptions and Practices of General Practitioners towards Oral Cancer and Emerging Risk Factors among Indian Immigrants in Australia: A Qualitative Study
Authors: Saraswat Nidhi , Pillay Rona , Prabhu Neeta , Everett Bronwyn , George Ajesh
Published: October 2021

Background: In Australia, Indian immigrants are one of the fastest-growing communities. Since oral cancer is widespread in India, the indulgence of Indians in customs of areca (betel) nut use in Australia may be linked to the recent rise in oral cancer cases. Since GPs (general practitioners) are primary healthcare providers, it is pivotal to ensure the oral cancer awareness of GPs. This study aimed to explore oral cancer risk-related knowledge, beliefs, and clinical practices of GPs in Australia. Methods: Fourteen semi-structured interviews were conducted with GPs practicing across New South Wales and Victoria. Purposive and snowball sampling were used for recruitment. Data were analysed through a directed content analysis approach. Results: All GPs were knowledgeable of major oral cancer causative factors including tobacco and alcohol, but some had limited understanding about the risks associated with areca nut preparations. Positive attitudes were evident, with all participants acknowledging the importance of oral cancer risk assessment. Most GPs recalled not performing oral cancer routine check-ups. Conclusion: GPs presented good oral cancer knowledge except for emerging risk factors such as areca nut use. Varied beliefs and inconsistent clinical practices relating to oral cancer screening is concerning. Accessible oral cancer training around emerging risk factors may benefit GPs.
Correction: Kwiatosz-Muc et al. Personality Traits and the Sense of Self-Efficacy among Nurse Anaesthetists. Multi-Centre Questionnaire Survey. Int. J. Environ. Res. Public Health 2021, 18, 9381
Authors: Kwiatosz-Muc Magdalena , Kotus Marzena , Aftyka Anna
Published: October 2021

There was an error in the original article [...]
Influenza Vaccination Programs for Healthcare Personnel: Organizational Issues and Beyond
Authors: Maltezou Helena C. , Ioannidou Eleni , De Schrijver Koen , François Guido , De Schryver Antoon
Published: October 2021

Healthcare personnel (HCP) are a high priority group for influenza vaccination aiming to protect them but also to protect vulnerable patients and healthcare services from healthcare-associated influenza and HCP absenteeism. Multi-component influenza vaccination programs targeting behavioral, organizational, and administrative barriers are critical, if influenza vaccination rates among HCP are to be raised on a sustained basis. Mandatory influenza vaccination policy is the only single intervention that can achieve high and sustainable vaccination rates in HCP in short term. In this article, we provide an overview of issues pertaining to influenza vaccination of HCP, with an emphasis on organizational issues of influenza vaccination programs.
Application of an Automatic Medical Information System to Implement Bundle Care for the Prevention of Ventilator-Associated Pneumonia
Authors: Lee Hung-Hui , Lin Li-Ying , Yang Hsiu-Fen , Tang Yu-Yi , Wang Pei-Hern
Published: October 2021

Ventilator-associated pneumonia is a common hospital-acquired infection. It causes patients to stay longer in the hospital and increases medical costs. This study explores the effect of applying an automatic medical information system to implement five-item prevention care bundles on the prevention of ventilator-related pneumonia. This study was a retrospective cohort study. This study was conducted from October 2017 to February 2018 and collected data from the intensive care unit of a medical center in southern Taiwan from January 2013 to May 2016. The control group (enrolled from January 2013 to June 2014) received oral hygiene. The experimental group (enrolled from July 2014 to December 2015) received five-item ventilator-associated pneumonia prevention care bundles, which consisted of (1) elevation of the head of the bed to 30–45°; (2) daily oral care with 0.12−0.2% chlorhexidine twice daily; (3) daily assessment of readiness to extubate; (4) daily sedative interruption; and (5) emptying water from the respirator tube. Results showed the incidence of ventilator-associated pneumonia in the bundle group was significantly less than the oral hygiene group (p = 0.029). The factors that significantly affected the incidence of ventilator-associated pneumonia were ventilator-associated pneumonia care bundle, ventilator-days, and intensive care unit length of stay. A significant reduction in ventilator-associated pneumonia rate in the bundle group compared to the oral hygiene group (OR = 0.366, 95% CI = 0.159–0.840) was observed, with 63.4% effectiveness. Application of an automatic medical information system to implement bundle care can significantly reduce the incidence of ventilator-associated pneumonia.
Editorial of Special Issue “Non-Coding RNAs in Pathogen-Host Interaction”
Authors: Lee Yong Sun
Published: October 2021

Clinical outcomes after pathologic infection are variable in infected individuals, ranging from no symptoms, moderate symptoms, hospitalization, and even death [...]
Biphalin—A Potent Opioid Agonist—As a Panacea for Opioid System-Dependent Pathophysiological Diseases?
Authors: Redkiewicz Patrycja , Dyniewicz Jolanta , Misicka Aleksandra
Published: October 2021

Biphalin, one of the opioid agonists, is a dimeric analog of enkephalin with a high affinity for opioid receptors. Opioid receptors are widespread in the central nervous system and in peripheral neuronal and non-neuronal tissues. Hence, these receptors and their agonists, which play an important role in pain blocking, may also be involved in the regulation of other physiological functions. Biphalin was designed and synthesized in 1982 by Lipkowski as an analgesic peptide. Extensive further research in various laboratories on the antinociceptive effects of biphalin has shown its excellent properties. It has been demonstrated that biphalin exhibits an analgesic effect in acute, neuropathic, and chronic animal pain models, and is 1000 times more potent than morphine when administered intrathecally. In the course of the broad conducted research devoted primarily to the antinociceptive effect of this compound, it has been found that biphalin may also potentially participate in the regulation of other opioid system-dependent functions. Nearly 40 years of research on the properties of biphalin have shown that it may play a beneficial role as an antiviral, antiproliferative, anti-inflammatory, and neuroprotective agent, and may also affect many physiological functions. This integral review analyzes the literature on the multidirectional biological effects of biphalin and its potential in the treatment of many opioid system-dependent pathophysiological diseases.
The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity
Authors: Serek Paweł , Oleksy-Wawrzyniak Monika
Published: October 2021

The intestinal barrier plays an extremely important role in maintaining the immune homeostasis of the gut and the entire body. It is made up of an intricate system of cells, mucus and intestinal microbiota. A complex system of proteins allows the selective permeability of elements that are safe and necessary for the proper nutrition of the body. Disturbances in the tightness of this barrier result in the penetration of toxins and other harmful antigens into the system. Such events lead to various digestive tract dysfunctions, systemic infections, food intolerances and autoimmune diseases. Pathogenic and probiotic bacteria, and the compounds they secrete, undoubtedly affect the properties of the intestinal barrier. The discovery of zonulin, a protein with tight junction regulatory activity in the epithelia, sheds new light on the understanding of the role of the gut barrier in promoting health, as well as the formation of diseases. Coincidentally, there is an increasing number of reports on treatment methods that target gut microbiota, which suggests that the prevention of gut-barrier defects may be a viable approach for improving the condition of COVID-19 patients. Various bacteria–intestinal barrier interactions are the subject of this review, aiming to show the current state of knowledge on this topic and its potential therapeutic applications.
The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors
Authors: Velichinskii Rodion A. , Streltsova Maria A. , Kust Sofya A. , Sapozhnikov Alexander M. , Kovalenko Elena I.
Published: October 2021

NK cells are an attractive target for cancer immunotherapy due to their potent antitumor activity. The main advantage of using NK cells as cytotoxic effectors over T cells is a reduced risk of graft versus host disease. At present, several variants of NK-cell-based therapies are undergoing clinical trials and show considerable effectiveness for hematological tumors. In these types of cancers, the immune cells themselves often undergo malignant transformation, which determines the features of the disease. In contrast, the current use of NK cells as therapeutic agents for the treatment of solid tumors is much less promising. Most studies are at the stage of preclinical investigation, but few progress to clinical trials. Low efficiency of NK cell migration and functional activity in the tumor environment are currently considered the major barriers to NK cell anti-tumor therapies. Various therapeutic combinations, genetic engineering methods, alternative sources for obtaining NK cells, and other techniques are aiming at the development of promising NK cell anticancer therapies, regardless of tumorigenesis. In this review, we compare the role of NK cells in the pathogenesis of hematological and solid tumors and discuss current prospects of NK-cell-based therapy for hematological and solid tumors.
Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar
Authors: Muñoz David , Fuentes Ricardo , Carnicero Beatriz , Aguilar Andrea , Sanhueza Nataly , San-Martin Sergio , Agurto Cristian , Donoso Andrea , Valdivia Leonardo E. , Miguez Jesús M. , Tort Lluis , Boltana Sebastián
Published: October 2021

The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic–pituitary–adrenocortical axes in stress-induced food intake behavior in fish.
Nanomicellar Extraction of Polyphenols—Methodology and Applications Review
Authors: Śliwa Paweł , Śliwa Karolina
Published: October 2021

The selection of the appropriate extraction method is crucial, especially for the receiving of active substances from plant material. The extraction using supercritical liquids and micellar-mediated extraction (MME) is the most advantageous among the alternative methods to classical solid–liquid extraction. However, the latter seems to be the best solution when the desired actives are polar. The following article presents a comprehensive review of the micellar-mediated extraction method in the last decade. The theoretical principle of the process was also refreshed and the current state of knowledge on the applications for analytical and manufacturing purposes was summarized.
Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions
Authors: Rincón-Riveros Andrés , Morales Duvan , Rodríguez Josefa Antonia , Villegas Victoria E. , López-Kleine Liliana
Published: October 2021

Noncoding RNAs (ncRNAs) play prominent roles in the regulation of gene expression via their interactions with other biological molecules such as proteins and nucleic acids. Although much of our knowledge about how these ncRNAs operate in different biological processes has been obtained from experimental findings, computational biology can also clearly substantially boost this knowledge by suggesting possible novel interactions of these ncRNAs with other molecules. Computational predictions are thus used as an alternative source of new insights through a process of mutual enrichment because the information obtained through experiments continuously feeds through into computational methods. The results of these predictions in turn shed light on possible interactions that are subsequently validated experimentally. This review describes the latest advances in databases, bioinformatic tools, and new in silico strategies that allow the establishment or prediction of biological interactions of ncRNAs, particularly miRNAs and lncRNAs. The ncRNA species described in this work have a special emphasis on those found in humans, but information on ncRNA of other species is also included.
Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity
Authors: Wang Chiung-Min , Yang William Harry , Cardoso Leticia , Gutierrez Ninoska , Yang Richard Henry , Yang Wei-Hsiung
Published: October 2021

Activating transcription factor 3 (ATF3), a transcription factor and acute stress sensor, is rapidly induced by a variety of pathophysiological signals and is essential in the complex processes in cellular stress response. FOXP3, a well-known breast and prostate tumor suppressor from the X chromosome, is a novel transcriptional repressor for several oncogenes. However, it remains unknown whether ATF3 is the target protein of FOXP3. Herein, we demonstrate that ATF3 expression is regulated by FOXP3. Firstly, we observed that overexpression of FOXP3 reduced ATF3 protein level. Moreover, knockdown FOXP3 by siRNA increased ATF3 expression. Secondly, FOXP3 dose-dependently reduced ATF3 promoter activity in the luciferase reporter assay. Since FOXP3 is regulated by post-translational modifications (PTMs), we next investigated whether PTMs affect FOXP3-mediated ATF3 expression. Interestingly, we observed that phosphorylation mutation on FOXP3 (Y342F) significantly abolished FOXP3-mediated ATF3 expression. However, other PTM mutations on FOXP3, including S418 phosphorylation, K263 acetylation and ubiquitination, and K268 acetylation and ubiquitination, did not alter FOXP3-mediated ATF3 expression. Finally, the FOXP3 binding site was found on ATF3 promoter region by deletion and mutagenesis analysis. Taken together, our results suggest that FOXP3 functions as a novel regulator of ATF3 and that this novel event may be involved in tumor development and progression.
5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
Authors: Hashimoto Takaaki , Sugihara Takaaki , Kanda Tsutomu , Takata Tomoaki , Isomoto Hajime
Published: October 2021

Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 μM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 μM) was added with PA. The gene expression levels of the nuclear factor erythroid 2–related factor 2 (NRF2), HO-1, Glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), C/EBP homologous protein (CHOP), and B-cell lymphoma 2 (BCL-2) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased GRP78 expression in Huh-7 cells. 5-ALA significantly induced HO-1 and decreased GRP78 expression. ATF6 was subsequently decreased. However, NRF2 and CHOP expression were not altered. Anti-apoptotic BCL-2 expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating GRP78 via HO-1 induction.
NLRP2 Is Overexpressed in Spinal Astrocytes at the Peak of Mechanical Pain Sensitivity during Complete Freund Adjuvant-Induced Persistent Pain
Authors: Ducza László , Szücs Péter , Hegedűs Krisztina , Bakk Erzsébet , Gajtkó Andrea , Wéber Ildikó , Holló Krisztina
Published: October 2021

Our earlier findings revealed that interleukin-1 receptor type-1 (IL-1R1) was overexpressed in spinal neurons, and IL-1R1-deficient mice showed significant attenuation of thermal and mechanical allodynia during the course of the Complete Freund adjuvant (CFA)-induced persistent pain model. In the present study, we found that a ligand of IL-1R1, termed interleukin-1β (IL-1β), is also significantly overexpressed at the peak of mechanical pain sensitivity in the CFA-evoked pain model. Analysis of cellular distribution and modeling using IMARIS software showed that in the lumbar spinal dorsal horn, IL-1β is significantly elevated by astrocytic expression. Maturation of IL-1β to its active form is facilitated by the formation of the multiprotein complex called inflammasome; thus, we tested the expression of NOD-like receptor proteins (NLRPs) in astrocytes. At the peak of mechanical allodynia, we found expression of the NLRP2 inflammasome sensor and its significantly elevated co-localization with the GFAP astrocytic marker, while NLRP3 was moderately present and NLRP1 showed total segregation from the astrocytic profiles. Our results indicate that peripheral CFA injection induces NLRP2 inflammasome and IL-1β expression in spinal astrocytes. The release of mature IL-1β can contribute to the maintenance of persistent pain by acting on its neuronally expressed receptor, which can lead to altered neuronal excitability.
Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes
Authors: Lim Sung Ho , Lee Ho Seon , Han Hyo-Kyung , Choi Chang-Ik
Published: October 2021

Obesity is a lipid metabolism disorder caused by genetic, medicinal, nutritional, and other environmental factors. It is characterized by a complex condition of excess lipid accumulation in adipocytes. Adipogenesis is a differentiation process that converts preadipocytes into mature adipocytes and contributes to excessive fat deposition. Saikosaponin A (SSA) and saikosaponin D (SSD) are triterpenoid saponins separated from the root of the Bupleurum chinensis, which has long been used to treat inflammation, fever, and liver diseases. However, the effects of these constituents on lipid accumulation and obesity are poorly understood. We investigated the anti-obesity effects of SSA and SSD in mouse 3T3-L1 adipocytes. The MTT assay was performed to measure cell viability, and Oil Red O staining was conducted to determine lipid accumulation. Various adipogenic transcription factors were evaluated at the protein and mRNA levels by Western blot assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Here, we showed that SSA and SSD significantly inhibited lipid accumulation without affecting cell viability within the range of the tested concentrations (0.938–15 µM). SSA and SSD also dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and adiponectin. Furthermore, the decrease of these transcriptional factors resulted in the repressed expression of several lipogenic genes including fatty acid binding protein (FABP4), fatty acid synthase (FAS), and lipoprotein lipase (LPL). In addition, SSA and SSD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), and inhibited the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). These results suggest that SSA and SSD inhibit adipogenesis through the AMPK or mitogen-activated protein kinase (MAPK) pathways in the early stages of adipocyte differentiation. This is the first study on the anti-adipogenic effects of SSA and SSD, and further research in animals and humans is necessary to confirm the potential of saikosaponins as therapeutic agents for obesity.
Fibronectin Molecular Status in Plasma of Women with Endometriosis and Fertility Disorders
Authors: Lis-Kuberka Jolanta , Kubik Paulina , Chrobak Agnieszka , Pająk Jarosław , Chełmońska-Soyta Anna , Orczyk-Pawiłowicz Magdalena
Published: October 2021

The diagnosis of endometriosis and fertility disorders is difficult; therefore, it is necessary to look for reliable biomarkers. Analysis of the molecular status of fibronectin as a key player in repair and wound healing processes, as well as in coagulation and fibrinolysis pathways, is justified. ELISA and SDS-agarose immunoblotting were applied to determine the fibronectin concentration and presence and occurrence of soluble FN-fibrin complexes in the blood plasma of women with endometriosis (n = 38), fertility disorders (n = 28) and the healthy group (n = 25). The concentration of fibronectin in the blood plasma of women with endometriosis (292.61 ± 96.17 mg/L) and fertility disorders (287.53 ± 122.68 mg/L) was significantly higher than in the normal group (226.55 ± 91.98 mg/L). The presence of FN-fibrin complexes of 750, 1000, 1300, 1600 and 1900 kDa in the plasma of women with endometriosis and fertility disorders was shown. The presence of FN-fibrin complexes with a molecular mass of more than 1300 kDa in women with endometriosis and infertility and the complete absence of these complexes in healthy women may indicate an increased and chronic activation of coagulation mechanisms in these patients. The presence of complexes of high molecular mass may be one of the biomarkers of fertility disorders in women.
Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
Authors: Zhong Cheng , Xu Minze , Boral Sengül , Summer Holger , Lichtenberger Falk-Bach , Erdoğan Cem , Gollasch Maik , Golz Stefan , Persson Pontus B. , Schleifenbaum Johanna , Patzak Andreas , Khedkar Pratik H.
Published: October 2021

Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10−6 mol L−1) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10−6 mol L−1) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.
The Overexpression of NUC Promotes Development and Increases Resistance to Nitrogen Deficiency in Arabidopsis thaliana
Authors: Ling Jing , Huang Xing , Jia Yanxia , Li Weiqi , Zhang Xudong
Published: October 2021

NUTCRACKER (NUC) is a transcription factor expressed in multiple tissues, but little is known about its physiological roles. In this study, we explored the physiological function of NUC with the Arabidopsis knockout, rescue, and overexpression lines. We found that NUC overexpression promoted development at the germination, seedling, and juvenile stages. NUC overexpression increased resistance to nitrogen (N) deficiency stress by increasing the chlorophyll content, suppressing anthocyanin accumulation, and increasing the biomass under N deficiency. In contrast, the absence of NUC did not affect such characteristics. N deficiency significantly increased the expression of NUC in leaves but did not affect the expression of NUC in roots. The overexpression of NUC promoted primary root length under both normal and N deficiency conditions. Furthermore, we found that the N-responsive and lateral-root-related genes TGA1 and NRT2.4 had NUC-binding sites in their promoter regions and that their expression was upregulated by NUC under N deficiency. The overexpression of the NUC increased the number and length of the lateral roots under N deficiency through inducible promotion. Multiple lines of investigation suggest that the regulatory function of the NUC could be bypassed through its redundant MAGPIE (MGP) when the NUC is absent. Our findings provide novel insight into NUC’s functions and will assist efforts to improve plants’ development and resistance to nutrient stresses.
Role of Energy Metabolism in the Progression of Neuroblastoma
Authors: Sakowicz-Burkiewicz Monika , Pawełczyk Tadeusz , Zyśk Marlena
Published: October 2021

Neuroblastoma is a common childhood cancer possessing a significant risk of death. This solid tumor manifests variable clinical behaviors ranging from spontaneous regression to widespread metastatic disease. The lack of promising treatments calls for new research approaches which can enhance the understanding of the molecular background of neuroblastoma. The high proliferation of malignant neuroblastoma cells requires efficient energy metabolism. Thus, we focus our attention on energy pathways and their role in neuroblastoma tumorigenesis. Recent studies suggest that neuroblastoma-driven extracellular vesicles stimulate tumorigenesis inside the recipient cells. Furthermore, proteomic studies have demonstrated extracellular vesicles (EVs) to cargo metabolic enzymes needed to build up a fully operative energy metabolism network. The majority of EV-derived enzymes comes from glycolysis, while other metabolic enzymes have a fatty acid β-oxidation and tricarboxylic acid cycle origin. The previously mentioned glycolysis has been shown to play a primary role in neuroblastoma energy metabolism. Therefore, another way to modify the energy metabolism in neuroblastoma is linked with genetic alterations resulting in the decreased activity of some tricarboxylic acid cycle enzymes and enhanced glycolysis. This metabolic shift enables malignant cells to cope with increasing metabolic stress, nutrition breakdown and an upregulated proliferation ratio.
Quality Assessment Methods for Textual Conversational Interfaces: A Multivocal Literature Review
Authors: Coppola Riccardo , Ardito Luca
Published: October 2021

The evaluation and assessment of conversational interfaces is a complex task since such software products are challenging to validate through traditional testing approaches. We conducted a systematic Multivocal Literature Review (MLR), on five different literature sources, to provide a view on quality attributes, evaluation frameworks, and evaluation datasets proposed to provide aid to the researchers and practitioners of the field. We came up with a final pool of 118 contributions, including grey (35) and white literature (83). We categorized 123 different quality attributes and metrics under ten different categories and four macro-categories: Relational, Conversational, User-Centered and Quantitative attributes. While Relational and Conversational attributes are most commonly explored by the scientific literature, we testified a predominance of User-Centered Attributes in industrial literature. We also identified five different academic frameworks/tools to automatically compute sets of metrics, and 28 datasets (subdivided into seven different categories based on the type of data contained) that can produce conversations for the evaluation of conversational interfaces. Our analysis of literature highlights that a high number of qualitative and quantitative attributes are available in the literature to evaluate the performance of conversational interfaces. Our categorization can serve as a valid entry point for researchers and practitioners to select the proper functional and non-functional aspects to be evaluated for their products.