bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of the Potential Mechanism of Tao Hong Si Wu Decoction for the Treatment of Breast Cancer Based on Network Pharmacology and In Vitro Experimental Verification
Authors: Huang Shi , Chen Yan , Pan Lingyu , Fei Changyi , Wang Ni , Chu Furui , Peng Daiyin , Duan Xianchun , Wang Yongzhong
Published: August 2021

Background

Tao Hong Si Wu Decoction (THSWD) is a well-known traditional Chinese medicine used clinically alone or combined with drugs to treat breast cancer. However, there has been no study to date on the underlying mechanisms of its therapeutic effects.

Objectives

To explore the potential mechanism of THSWD for the treatment of breast cancer using network pharmacology and experimental research.

Methods

The active ingredients of THSWD were screened according to Lipinski’s rule of five based on the 107 ingredients of THSWD identified by UPLC-Q-TOF-MSE. The targets of THSWD and breast cancer from multiple databases were collected, and a Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Gene ontology (GO) analysis and KEGG pathway analysis were performed via the DAVID server. Molecular docking studies verified the selected key ingredients and key targets. The results of network pharmacology were verified by in vitro experiments. Including the effects of THSWD drug-containing rat serum (THSWD serum) on cell proliferation, and on the targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 were assayed by RT-qPCR and Western blot assays.

Results

In total, 27 active ingredients including 8 core components, were obtained from 107 ingredients and 218 THSWD target genes for the treatment of breast cancer were identified. THSWD is active in the treatment of breast cancer by targeting Ras, FoxO, PI3K-Akt and other signaling pathways. MCF-7 and MDA-MB-231 cell proliferation was inhibited by THSWD serum in a time and concentration dependent manner. THSWD could regulated the RNA and protein expression of core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 for treatment of breast cancer.

Conclusion

The results of network pharmacology study showed that THSWD is active against breast cancer by intervening with multiple targets and pathways. Luteolin, kaempferol, senkyunolide E, and other 8 compounds may be the core active ingredients of THSWD in the treatment of breast cancer. THSWD treatment of breast cancer may be related to targeting Ras, FoxO, PI3K-Akt, and other signal pathways associated with the core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14.
Attention-Based Fault-Tolerant Approach for Multi-Agent Reinforcement Learning Systems
Authors: Gu Shanzhi , Geng Mingyang , Lan Long
Published: August 2021

The aim of multi-agent reinforcement learning systems is to provide interacting agents with the ability to collaboratively learn and adapt to the behavior of other agents. Typically, an agent receives its private observations providing a partial view of the true state of the environment. However, in realistic settings, the harsh environment might cause one or more agents to show arbitrarily faulty or malicious behavior, which may suffice to allow the current coordination mechanisms fail. In this paper, we study a practical scenario of multi-agent reinforcement learning systems considering the security issues in the presence of agents with arbitrarily faulty or malicious behavior. The previous state-of-the-art work that coped with extremely noisy environments was designed on the basis that the noise intensity in the environment was known in advance. However, when the noise intensity changes, the existing method has to adjust the configuration of the model to learn in new environments, which limits the practical applications. To overcome these difficulties, we present an Attention-based Fault-Tolerant (FT-Attn) model, which can select not only correct, but also relevant information for each agent at every time step in noisy environments. The multihead attention mechanism enables the agents to learn effective communication policies through experience concurrent with the action policies. Empirical results showed that FT-Attn beats previous state-of-the-art methods in some extremely noisy environments in both cooperative and competitive scenarios, much closer to the upper-bound performance. Furthermore, FT-Attn maintains a more general fault tolerance ability and does not rely on the prior knowledge about the noise intensity of the environment.
Learning from Scarce Information: Using Synthetic Data to Classify Roman Fine Ware Pottery
Authors: Núñez Jareño Santos J. , van Helden Daniël P. , Mirkes Evgeny M. , Tyukin Ivan Y. , Allison Penelope M.
Published: August 2021

In this article, we consider a version of the challenging problem of learning from datasets whose size is too limited to allow generalisation beyond the training set. To address the challenge, we propose to use a transfer learning approach whereby the model is first trained on a synthetic dataset replicating features of the original objects. In this study, the objects were smartphone photographs of near-complete Roman terra sigillata pottery vessels from the collection of the Museum of London. Taking the replicated features from published profile drawings of pottery forms allowed the integration of expert knowledge into the process through our synthetic data generator. After this first initial training the model was fine-tuned with data from photographs of real vessels. We show, through exhaustive experiments across several popular deep learning architectures, different test priors, and considering the impact of the photograph viewpoint and excessive damage to the vessels, that the proposed hybrid approach enables the creation of classifiers with appropriate generalisation performance. This performance is significantly better than that of classifiers trained exclusively on the original data, which shows the promise of the approach to alleviate the fundamental issue of learning from small datasets.
Biomass Fast Pyrolysis Vapor Upgrading over γ-Alumina, Hydrotalcite, Dolomite and Effect of Na2CO3 Loading: A Pyro Probe GCMS Study
Authors: Mysore Prabhakara Harsha , Bramer Eddy , Brem Gerrit
Published: August 2021

The influence of γ-alumina, hydrotalcite, dolomite and Na2CO3 loaded γ-alumina, hydrotalcite, dolomite on fast pyrolysis vapor upgrading of beechwood was investigated using an analytical pyro probe-gas chromatography/mass spectrometry instrument (Py-GC/MS) at a temperature of 500 °C. Overall, this research showcased that these catalysts can deoxygenate biomass pyrolysis vapors into a mixture of intermediate compounds which have substantially lower oxygen content. The intermediate compounds are deemed to be suitable for downstream hydrodeoxygenation processes and it also means that hydrogen consumption will be reduced as a result of moderate in-situ deoxygenation. Among the support catalysts, the application of hydrotalcite yielded the best results with the formation of moderately deoxygenated compounds such as light phenols, mono-oxy ketones, light furans and hydrocarbons with a TIC area % of 7.5, 44.8, 9.8 and 9.8, respectively. In addition, acids were considerably reduced. Dolomite was the next most effective catalyst as γ-alumina retained most of the acids and other oxygenates. Na2CO3 loading on γ-alumina had a noticeable effect on eliminating more or less all the acids, enhancing the mono-oxy-ketones and producing lighter furans. In contrast, Na2CO3 loading on dolomite and hydrotalcite did not show a major impact on the composition except for further enhancing the mono-oxy-ketones (e.g., acetone and cyclopentenones). Additionally, in the case of hydrotalcite and γ-alumina, Na2CO3 loading suppressed the formation of hydrocarbons. In this research, the composition of pyrolytic vapors as a result of catalysis is elaborated further under the specific oxygenate groups such as acids, phenolics, furanics, ketones and acids. Further the catalysts were also characterized by BET, XRD and TGA analysis.
Effect of Biodiesel Blends on the Transient Performance of Compression Ignition Engines
Authors: Tesfa Belachew Cekene , Mishra Rakesh , Aliyu Aliyu M.
Published: August 2021

Prior to full electric conversion, internal combustion engines will still maintain a paramount position in heavy goods and earth-moving vehicles. The most promising, cleaner alternative to fossil fuels is biodiesel. While it does not require alterations in the engine design, hence no major overhaul of existing infrastructure, biodiesel is more sustainable and clean-burning than petro-diesel. Extensive research has been reported on the effect of biodiesel blends, on the operational characteristics of compression ignition (CI) engines as well as the emissions behaviour of such engines. The performance characteristics of CI engines under transient operational conditions with Biodiesel blends has had limited attention so far from researchers. In the present work, transient performance characteristics of a CI engine has been evaluated for various biodiesel blends and its effects on performance behaviour have been quantified. In addition, emission footprints of CI engines under various transient operational conditions have also been enumerated.
Food Insecurity and Eating Pathology in Adolescents
Authors: Kim Brittany H. , Ranzenhofer Lisa , Stadterman Jill , Karvay Yvette G. , Burke Natasha L.
Published: August 2021

Adolescence is a critical period for the emergence of eating disorders, and food insecurity may be related to eating pathology and weight, as evidenced in adults. However, little is known about food insecurity and eating pathology during this developmental period, and associations between food insecurity and body mass index (BMI) are mixed. Therefore, we examined associations between food insecurity and BMI percentile, self-reported eating-related pathology and binge eating, and subgroup differences by race/ethnicity. In a subset, we examined the relationship between food insecurity and real-world hunger, food craving, and loss-of-control eating using ecological momentary assessment (EMA). Fifty-eight adolescents at two sites (clinical sample, n = 38, BMI percentile ≥ 70th; community sample, n = 20, all BMI strata) completed self-report questionnaires. Adolescents were 15.2 ± 2.1 years old, 62% female, 50% Black, 34.5% Hispanic, with BMI percentile = 80.5 ± 25.8 (range 4–99). In the full sample, food insecurity was associated with greater BMI (p < 0.01), higher shape/weight overvaluation (p = 0.04), and greater number of binge eating episodes among those reporting at least one binge episode (p < 0.01), with significant relationships for BMI percentile, shape/weight overvaluation, body dissatisfaction, and binge episode frequency among Hispanic adolescents only (each p < 0.01). As in adults, food insecurity may be a risk factor for eating pathology, particularly for Hispanic teens.
Prevalence of Psychological Impacts on Healthcare Providers during COVID-19 Pandemic in Asia
Authors: Norhayati Mohd Noor , Che Yusof Ruhana , Azman Mohd Yacob
Published: August 2021

COVID-19 has impacted people psychologically globally, including healthcare providers. Anxiety, depression, and stress are the most common impacts that have affected these people. Thus, this study was aimed to ascertain the estimated prevalence of psychological impacts among healthcare providers in the Asian region. A systematic search was performed in the MEDLINE, CINAHL, and Scopus databases for original research articles published between 2020 and April 2021. Only studies published in English were included. The quality of data was assessed using the Joanna Briggs Institute Meta-Analysis, and the analysis was performed using generic inverse variance with a random-effects model by Review Manager software. A total of 80 studies across 18 countries in Asia region were pooled to assess the data prevalence on anxiety (34.81% (95% CI: 30.80%, 38.83%)), depression (34.61% (95% CI: 30.87%, 38.36%)), stress (31.72% (95% CI: 21.25%, 42.18%)), insomnia (37.89% (95% CI: 25.43%, 50.35%)), and post-traumatic stress disorder (15.29% (95% CI: 11.43%, 19.15%)). Subgroup analyses were conducted across regions, type of healthcare providers, sex, and occupation. This review has identified a high prevalence of anxiety, depression, stress, and insomnia but a low prevalence of post-traumatic stress disorder among healthcare providers in Asia regions. Effective intervention support programs are urgently needed to improve psychological health of healthcare providers and maintaining the health system.
A Statistical Model to Assess Risk for Supporting COVID-19 Quarantine Decisions
Authors: Jäckle Sonja , Röger Elias , Dicken Volker , Geisler Benjamin , Schumacher Jakob , Westphal Max
Published: August 2021

In Germany, local health departments are responsible for surveillance of the current pandemic situation. One of their major tasks is to monitor infected persons. For instance, the direct contacts of infectious persons at group meetings have to be traced and potentially quarantined. Such quarantine requirements may be revoked, when all contact persons obtain a negative polymerase chain reaction (PCR) test result. However, contact tracing and testing is time-consuming, costly and not always feasible. In this work, we present a statistical model for the probability that no transmission of COVID-19 occurred given an arbitrary number of negative test results among contact persons. Hereby, the time-dependent sensitivity and specificity of the PCR test are taken into account. We employ a parametric Bayesian model which combines an adaptable Beta-Binomial prior and two likelihood components in a novel fashion. This is illustrated for group events in German school classes. The first evaluation on a real-world dataset showed that our approach can support important quarantine decisions with the goal to achieve a better balance between necessary containment of the pandemic and preservation of social and economic life. Future work will focus on further refinement and evaluation of quarantine decisions based on our statistical model.
Associations between Physical Activity, Sitting Time, and Time Spent Outdoors with Mental Health during the First COVID-19 Lock Down in Austria
Authors: Haider Sandra , Smith Lee , Markovic Lovro , Schuch Felipe B. , Sadarangani Kabir P. , Lopez Sanchez Guillermo Felipe , Lopez-Bueno Rubén , Gil-Salmerón Alejandro , Rieder Anita , Tully Mark A. , Tschiderer Lena , Seekircher Lisa , Willeit Peter , Grabovac Igor
Published: August 2021

Measures implemented to reduce the spread of SARS-CoV-2 have resulted in a decrease in physical activity (PA) while sedentary behaviour increased. The aim of the present study was to explore associations between PA and mental health in Austria during COVID-19 social restrictions. In this web-based cross-sectional study (April–May 2020) moderate-to-vigorous physical activity (MVPA), sitting time, and time spent outdoors were self-reported before and during self-isolation. Mental well-being was assessed with the Warwick-Edinburgh Mental Well-being Scale, and the Beck depression and anxiety inventories. The majority of the participants (n = 652) were female (72.4%), with a mean age of 36.0 years and a standard deviation (SD) of 14.4. Moreover, 76.5% took part in ≥30 min/day of MVPA, 53.5% sat ≥10 h/day, and 66.1% spent ≥60 min/day outdoors during self-isolation. Thirty-eight point five percent reported high mental well-being, 40.5% reported depressive symptoms, and 33.9% anxiety symptoms. Participating in higher levels of MVPA was associated with higher mental well-being (odds ratio = OR: 3.92; 95% confidence interval = 95%CI: 1.51–10.15), less depressive symptoms (OR: 0.44; 95%CI: 0.29–0.66) and anxiety symptoms (OR = 0.62; 95%CI: 0.41–0.94), and less loneliness (OR: 0.46; 95%CI: 0.31–0.69). Participants sitting <10 h/day had higher odds of mental well-being (OR: 3.58; 95%CI: 1.13–11.35). Comparable results were found for spending ≥60 min/day outdoors. Maintaining one’s MVPA levels was associated with higher mental well-being (OR = 8.61, 95%CI: 2.68–27.62). In conclusion, results show a positive association between PA, time spent outdoors and mental well-being during COVID-19 social restrictions. Interventions aiming to increase PA might mitigate negative effects of such restrictions.
A Study on Physical Exercise and General Mobility in People with Cerebral Palsy: Health through Costless Routines
Authors: Molina-Cantero Alberto J. , Merino-Monge Manuel , Castro-García Juan A. , Pousada-García Thais , Valenzuela-Muñoz David , Gutiérrez-Párraga Juan , López-Álvarez Setefilla , Gómez-González Isabel M.
Published: August 2021

Sedentary behavior (SB) is a common problem that may produce health issues in people with cerebral palsy (CP). When added to a progressive reduction in motor functions over time, SB can lead to higher percentages of body fat, muscle stiffness and associated health issues in this population. Regular physical activity (RPA) may prevent the loss of motor skills and reduce health risks. In this work, we analyzed data collected from 40 people (20 children and teenagers, and 20 adults) who attend two specialist centers in Seville to obtain an up-to-date picture regarding the practice of RPA in people with CP. Roughly 60% of the participants showed mostly mid/severe mobility difficulties, while 38% also had communicative issues. Most of the participants performed light-intensity physical activity (PA) at least once or twice a week and, in the majority of cases, had a neutral or positive attitude to exercising. In the Asociación Sevillana de Parálisis Cerebral (ASPACE) sample test, the higher the International Classification of Functioning, Disability and Health (ICF), the higher the percentage of negative responses to doing exercise. Conversely, in the Centro Específico de Educación Especial Mercedes Sanromá (CEEEMS), people likes PA but slightly higher ratios of positive responses were found at Gross Motor Function Classification System (GMFCS) levels V and II, agreeing with the higher personal engagement of people at those levels. We have also performed a literature review regarding RPA in CP and the use of low-cost equipment. As a conclusion, we found that RPA produces enormous benefits for health and motor functions, whatever its intensity and duration. Costless activities such as walking, running or playing sports; exercises requiring low-cost equipment such as elastic bands, certain smartwatches or video-games; or therapies with animals, among many others, have all demonstrated their suitability for such a purpose.
Socioeconomic Inequalities and Obesity in South Africa—A Decomposition Analysis
Authors: Goetjes Eva , Pavlova Milena , Hongoro Charles , Groot Wim
Published: August 2021

Background: Prior evidence shows that inequalities are related to overweight and obesity in South Africa. Using data from a recent national study, we examine the socioeconomic inequalities associated with obesity in South Africa and the factors associated with it. Methods: We use quantitative data from the South African National Health and Nutrition Examination Survey (SANHANES-1) carried out in 2012. We estimate the concentration index (CI) to identify inequalities and decompose the CI to explore the determinants of these inequalities. Results: We confirm the existence of pro-rich inequalities associated with obesity in South Africa. The inequalities among males are larger (CI of 0.16) than among women (CI of 0.09), though more women are obese than men. Marriage increases the risk of obesity for women and men, while smoking decreases the risk of obesity among men significantly. Higher education is associated with lower inequalities among females. Conclusions: We recommend policies to focus on promoting a healthy lifestyle, including the individual’s perception of a healthy body size and image, especially among women.
Exploring Tertiary Health Science Student Willingness or Resistance to Cultural Competency and Safety Pedagogy
Authors: Micheal Sowbhagya , Ogbeide Anita Eseosa , Arora Amit , Alford Stewart , Firdaus Rubab , Lim David , Dune Tinashe
Published: August 2021

There is an increasing body of literature that considers the relevance and experiences of cultural competency and safety training in health professional students. However, less is written about Australian tertiary learners’ experiences of engaging with cultural competency training. The aim of this study is to explore tertiary students’ willingness or resistance to cultural competency and safety pedagogy. Qualitative student feedback to a teaching unit was collected and triangulated with data from focus groups with tutors. Results were thematically analyzed. Willingness and resistance to cultural competency and safety teaching emerged as two key themes. Willingness to engage with the unit was largely due to student interest in the content, teaching environment and relevance of cultural competency to students’ future practice. Resistance was linked to the students feeling personally attacked, or culturally confronted, with tutors noting the topics around sexuality and white privilege being more resisted. Acknowledging reasons for student resistance and developing strategies to reduce resistance can facilitate more student engagement with cultural competency topics, ultimately leading to their future provision of culturally competent healthcare.
COVID-19 among Health Workers in Germany—An Update
Authors: Nienhaus Albert
Published: August 2021

This is an update of our report on COVID-19 among health and social welfare workers in Germany. Workers’ compensation claims for occupational diseases (OD) are recorded in a standardized database of the Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW). We analyzed which workers in the health and welfare sector are most often affected by COVID-19. For the different sectors in healthcare and welfare, the number of full-time workers is known (FTW), allowing for calculation of claim rates by sector. The period for data presentation was extended to 3 May 2021 for this update. The cumulative number of COVID-19 claims increased from 4398 by May 2020 to 84,728 by May 2021. The majority of claims concern nursing homes (39.5%) and hospitals (37.6%). Nursing is the profession most often concerned (68.8%). Relative to the number of workers, the claim rate is highest for hospitals (41.3/1000 FTW). Seventy-seven workers died (0.09%) and three hundred and seventy-five (0.4%) were hospitalized. A total of 65,693 (77.5%) claims were assessed, and for 81.4% of these claims, the OD was confirmed. The number of health and welfare workers affected by COVID-19 is high. With most HW vaccinated by now in Germany, within the next few weeks or months, the number of new cases should decrease.
Investigating the Molecular Processes behind the Cell-Specific Toxicity Response to Titanium Dioxide Nanobelts
Authors: Winckers Laurent A. , Evelo Chris T. , Willighagen Egon L. , Kutmon Martina
Published: August 2021

Some engineered nanomaterials incite toxicological effects, but the underlying molecular processes are understudied. The varied physicochemical properties cause different initial molecular interactions, complicating toxicological predictions. Gene expression data allow us to study the responses of genes and biological processes. Overrepresentation analysis identifies enriched biological processes using the experimental data but prompts broad results instead of detailed toxicological processes. We demonstrate a targeted filtering approach to compare public gene expression data for low and high exposure on three cell lines to titanium dioxide nanobelts. Our workflow finds cell and concentration-specific changes in affected pathways linked to four Gene Ontology terms (apoptosis, inflammation, DNA damage, and oxidative stress) to select pathways with a clear toxicity focus. We saw more differentially expressed genes at higher exposure, but our analysis identifies clear differences between the cell lines in affected processes. Colorectal adenocarcinoma cells showed resilience to both concentrations. Small airway epithelial cells displayed a cytotoxic response to the high concentration, but not as strongly as monocytic-like cells. The pathway-gene networks highlighted the gene overlap between altered toxicity-related pathways. The automated workflow is flexible and can focus on other biological processes by selecting other GO terms.
Molecular Imaging of Brown Adipose Tissue Mass
Authors: Yang Jing , Zhang Haili , Parhat Kadirya , Xu Hui , Li Mingshuang , Wang Xiangyu , Ran Chongzhao
Published: August 2021

Brown adipose tissue (BAT), a uniquely thermogenic tissue that plays an important role in metabolism and energy expenditure, has recently become a revived target in the fight against metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Different from white adipose tissue (WAT), the brown adipocytes have distinctive features including multilocular lipid droplets, a large number of mitochondria, and a high expression of uncoupling protein-1 (UCP-1), as well as abundant capillarity. These histologic characteristics provide an opportunity to differentiate BAT from WAT using imaging modalities, such as PET/CT, SPECT/CT, MRI, NIRF and Ultrasound. However, most of the reported imaging methods were BAT activation dependent, and the imaging signals could be affected by many factors, including environmental temperatures and the states of the sympathetic nervous system. Accurate BAT mass detection methods that are independent of temperature and hormone levels have the capacity to track the development and changes of BAT throughout the lifetime of mammals, and such methods could be very useful for the investigation of potential BAT-related therapies. In this review, we focus on molecular imaging modalities that can detect and quantify BAT mass. In addition, their detection mechanism and limitations will be discussed as well.
Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients
Authors: Pozo-Agundo Ana , Villaescusa Nerea , Martorell-Marugán Jordi , Soriano Olga , Leyva Socorro , Jódar-Reyes Ana Belén , Botella Luisa María , Carmona-Sáez Pedro , Blanco Francisco Javier
Published: August 2021

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. Here, we carried out a liquid biopsy by which we isolated total RNA from plasma exosome samples. A cohort of 15 HHT type 1 patients, 15 HHT type 2 patients, and 10 healthy relatives were analyzed. Upon gene expression data processing and normalization, a statistical analysis was performed to explore similarities in microRNA expression patterns among samples and detect differentially expressed microRNAs between HHT samples and the control group. We found a disease-associated molecular fingerprint of 35 miRNAs over-represented in HHT vs. controls, with eight being specific for HHT1 and 11 for HHT2; we also found 30 under-represented, including nine distinct for HHT1 and nine for HHT2. The analysis of the receiver operating characteristic (ROC) curves showed that eight miRNAs had good (AUC > 75%) or excellent (AUC > 90%) diagnosis value for HHT and even for type HHT1 and HHT2. In addition, we identified the cellular origin of these miRNAs among the cell types involved in the vascular malformations. Interestingly, we found that only some of them were incorporated into exosomes, which suggests a key functional role of these exosomal miRNAs in the pathophysiology of HHT.
Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane
Authors: Knop Jan , Lienemann Tim , El-Kilani Haifa , Falke Sven , Krings Catharina , Sindalovskaya Maria , Bergler Johannes , Betzel Christian , Hoth Stefan
Published: August 2021

Plant U-box armadillo repeat (PUB-ARM) ubiquitin (Ub) ligases have important functions in plant defense through the ubiquitination of target proteins. Defense against pathogens involves vesicle trafficking and the formation of extracellular vesicles. The PUB-ARM protein SENESCENCE ASSOCIATED UBIQUITIN E3 LIGASE1 (SAUL1) can form patches at the plasma membrane related to tethering multi-vesicular bodies (MVBs) to the plasma membrane. We uncovered the structure of a full-length plant ubiquitin ligase and the structural requirements of SAUL1, which are crucial for its function in patch formation. We resolved the structure of SAUL1 monomers by small-angle X-ray scattering (SAXS). The SAUL1 model showed that SAUL1 consists of two domains: a domain containing the N-terminal U-box and armadillo (ARM) repeats and the C-terminal ARM repeat domain, which includes a positively charged groove. We showed that all C-terminal ARM repeats are essential for patch formation and that this function requires arginine residue at position 736. By applying SAXS to polydisperse SAUL1 systems, the oligomerization of SAUL1 is detectable, with SAUL1 tetramers being the most prominent oligomers at higher concentrations. The oligomerization domain consists of the N-terminal U-box and some N-terminal ARM repeats. Deleting the U-box resulted in the promotion of the SAUL1 tethering function. Our findings indicate that structural changes in SAUL1 may be fundamental to its function in forming patches at the plasma membrane.
The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma
Authors: Della Bella Chiara , Soluri Maria Felicia , Puccio Simone , Benagiano Marisa , Grassi Alessia , Bitetti Jacopo , Cianchi Fabio , Sblattero Daniele , Peano Clelia , D’Elios Mario Milco
Published: August 2021

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.
Efficacy of a Topical Wound Agent Methanesulfonic Acid and Dimethylsulfoxide on In Vitro Biofilms
Authors: Schwarzer Saskia , Radzieta Michael , Jensen Slade O. , Malone Matthew
Published: August 2021

A topical desiccating wound agent containing methanesulfonic acid, dimethylsulfoxide and amorphous silica was evaluated in three in vitro models for its efficacy against biofilms produced by Pseudomonas aeruginosa (ATCC-15442) and Staphylococcus aureus (ATCC-6538). The in vitro biofilm models used were; the MBEC Assay®, Centre for Disease Control (CDC) Biofilm Reactor® and a Semi-solid biofilm model. A 30-s exposure of a topical wound desiccating agent was used in each model. A complete eradication of viable cells was demonstrated in all models for both strains (p < 0.0001). Imaging with scanning electron microscopy (SEM) was performed where possible. All three models demonstrated complete eradication of viable cells with a 30 s application of a topical wound desiccating agent.
The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases
Authors: Lowe Henry , Toyang Ngeh , Steele Blair , Bryant Joseph , Ngwa Wilfred
Published: August 2021

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.
Saringosterol from Sargassum fusiforme Modulates Cholesterol Metabolism and Alleviates Atherosclerosis in ApoE-Deficient Mice
Authors: Yan Ying , Niu Zhoumin , Wang Boyang , Zhao Shangge , Sun Chao , Wu Yuting , Li Yuying , Ying Hao , Liu Hongbing
Published: August 2021

Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and β are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRβ provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRβ, which we identified previously in edible marine seaweed Sargassum fusiforme. We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.
The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants
Authors: Lin Lisha , Li Sujuan , Gao Na , Wang Weili , Zhang Taocui , Yang Lian , Yang Xingzhi , Luo Dan , Ji Xu , Zhao Jinhua
Published: August 2021

Fucosylated glycosaminoglycan (FG) from sea cucumber is a potent anticoagulant by inhibiting intrinsic coagulation tenase (iXase). However, high-molecular-weight FGs can activate platelets and plasma contact system, and induce hypotension in rats, which limits its application. Herein, we found that FG from T. ananas (TaFG) and FG from H. fuscopunctata (HfFG) at 4.0 mg/kg (i.v.) could cause significant cardiovascular and respiratory dysfunction in rats, even lethality, while their depolymerized products had no obvious side effects. After injection, native FG increased rat plasma kallikrein activity and levels of the vasoactive peptide bradykinin (BK), consistent with their contact activation activity, which was assumed to be the cause of hypotension in rats. However, the hemodynamic effects of native FG cannot be prevented by the BK receptor antagonist. Further study showed that native FG induced in vivo procoagulation, thrombocytopenia, and pulmonary embolism. Additionally, its lethal effect could be prevented by anticoagulant combined with antiplatelet drugs. In summary, the acute toxicity of native FG is mainly ascribed to pulmonary microvessel embolism due to platelet aggregation and contact activation-mediated coagulation, while depolymerized FG is a safe anticoagulant candidate by selectively targeting iXase.
Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms
Authors: Wu Lichuan , Ye Ke , Jiang Sheng , Zhou Guangbiao
Published: August 2021

Worldwide, 19.3 million new cancer cases and almost 10.0 million cancer deaths occur each year. Recently, much attention has been paid to the ocean, the largest biosphere of the earth that harbors a great many different organisms and natural products, to identify novel drugs and drug candidates to fight against malignant neoplasms. The marine compounds show potent anticancer activity in vitro and in vivo, and relatively few drugs have been approved by the U.S. Food and Drug Administration for the treatment of metastatic malignant lymphoma, breast cancer, or Hodgkin′s disease. This review provides a summary of the anticancer effects and mechanisms of action of selected marine compounds, including cytarabine, eribulin, marizomib, plitidepsin, trabectedin, zalypsis, adcetris, and OKI-179. The future development of anticancer marine drugs requires innovative biochemical biology approaches and introduction of novel therapeutic targets, as well as efficient isolation and synthesis of marine-derived natural compounds and derivatives.
Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3
Authors: Yang Wencong , Tan Qi , Yin Yihao , Chen Yan , Zhang Yi , Wu Jianying , Gao Leyao , Wang Bo , She Zhigang
Published: August 2021

Eight new compounds, including two sambutoxin derivatives (1–2), two highly oxygenated cyclopentenones (7–8), four highly oxygenated cyclohexenones (9–12), together with four known sambutoxin derivatives (3–6), were isolated from semimangrove endophytic fungus Talaromyces sp. CY-3, under the guidance of molecular networking. The structures of new isolates were elucidated by analysis of detailed spectroscopic data, ECD spectra, chemical hydrolysis, 13C NMR calculation, and DP4+ analysis. In bioassays, compounds 1–5 displayed better α-glucosidase inhibitory activity than the positive control 1-deoxynojirimycin (IC50 = 80.8 ± 0.3 μM), and the IC50 value was in the range of 12.6 ± 0.9 to 57.3 ± 1.3 μM.
Early and Late Outcomes after Arterial Switch Operation: A 40-Year Journey in a Single Low Case Volume Center
Authors: Jonas Karolis , Jakutis Virginijus , Sudikienė Rita , Lebetkevičius Virgilijus , Baliulis Giedrius , Tarutis Virgilijus
Published: August 2021

Background and Objectives: The results of the arterial switch operation in large congenital heart centers are excellent, and the results in small and medium centers are improving. The objective of this article is to share our experience utilizing the international knowledge transfer program to improve early and late arterial switch operation outcomes in our center. Materials and Methods: A retrospective analysis of patients who underwent the arterial switch operation in Vilnius University Santaros Clinics Cardiothoracic Surgery Center between 1977–2020 was performed. Results: A total of 127 consecutive arterial switch operations were performed in our center. Surgical mortality during the entire study period was 24.6%. Surgical mortality prior to the program, during the program, and after the program was 88.24%, 41.7%, and 5.81%, respectively (p < 0.0001). The surgical mortality of patients operated on during the last 10 years was 4%. The overall survival estimate for the 97 surviving patients was 96.9%, 94.9%, 93.8%, 93.8%, 93.8%, 93.8% at 1, 3, 5, 10, 15, and 20 years, respectively. Risk factors for early mortality included longer aortic cross-clamp time and operation prior to the knowledge transfer program. The only significant risk factor for late reintervention was concomitant aortic arch obstruction treated at the time of the arterial switch. Conclusions: The surgical treatment of transposition of the great arteries by means of an arterial switch with good results can be possible in low-to-medium volume congenital heart surgery centers. International knowledge transfer programs between high-expertise high-volume congenital heart centers and low-to-medium volume congenital heart centers may help to shorten the learning curve and improve early and late outcomes after an arterial switch. The risk factors for surgical mortality and intervention-free survival in low-volume surgical centers are similar to those in high-volume centers. Late arterial switch-related complications are similar to those among different-sized congenital heart centers.
System for Monitoring Progress in a Mixing and Grinding Machine Using Sound Signal Processing
Authors: Wangkanklang Ekkawit , Koike Yoshikazu
Published: August 2021

In this paper we present a system for monitoring progress in a mixing and grinding machine via the signal processing of sound emitted by the machine. Our low-cost, low-maintenance system may improve automatic machines and the industrial Internet of Things. We used the Pumpkin Pi board and Raspberry Pi, which are low-cost hardware devices, for recording sounds via a microphone and analyzing the sound signals, respectively. Sound data obtained at regular intervals were compressed. The estimated power spectral density (PSD) values calculated from the sound signals were related to the status of the material during mixing and grinding. We examined the correlation between the PSD obtained by the STFT and the particle distributions in detail. We found that PSD values had both repeatability and a strong relation with the particle distributions that were created by the mixing and grinding machine, although the relation between the PSD and the particle size distributions was not merely linear. We used the PSD values to estimate the progress remotely during the operation of the machine.
The Early Adhesion Effects of Human Gingival Fibroblasts on Bovine Serum Albumin Loaded Hydrogenated Titanium Nanotube Surface
Authors: Sun Yuchen , Lu Ran , Liu Jingming , Wang Xin , Dong Haitao , Chen Su
Published: August 2021

The soft tissue sealing at the transmucal portion of implants is vital for the long-term stability of implants. Hydrogenated titanium nanotubes (H2-TNTs) as implant surface treatments were proved to promote the adhesion of human gingival fibroblasts (HGFs) and have broad usage as drug delivery systems. Bovine serum albumin (BSA) as the most abundant albumin in body fluid was crucial for cell adhesion and was demonstrated as a normal loading protein. As the first protein arriving on the surface of the implant, albumin plays an important role in initial adhesion of soft tissue cells, it is also a common carrier, transferring and loading different endogenous and exogenous substances, ions, drugs, and other small molecules. The aim of the present work was to investigate whether BSA-loaded H2-TNTs could promote the early adhesion of HGFs; H2-TNTs were obtained by hydrogenated anodized titanium dioxide nanotubes (TNTs) in thermal treatment, and BSA was loaded in the nanotubes by vacuum drying; our results showed that the superhydrophilicity of H2-TNTs is conducive to the loading of BSA. In both hydrogenated titanium nanotubes and non-hydrogenated titanium nanotubes, a high rate of release was observed over the first hour, followed by a period of slow and sustained release; however, BSA-loading inhibits the early adhesion of human gingival fibroblasts, and H2-TNTs has the best promoting effect on cell adhesion. With the release of BSA after 4 h, the inhibitory effect of BSA on cell adhesion was weakened.
Secondary Dopants of Electrically Conducting Polyanilines
Authors: Kim Young-Gi , Nguyen Hai-Long , Kinlen Patrick
Published: August 2021

Secondary dopants and the doping methods were identified for increasing the electrical conductivity of a highly processable and a primarily doped polyaniline dinonylnaphthalene sulfonic acid (PANI-DNNSA). The secondary doping was carried out using film, solution, and vapor doping methods. The doping methods and functional groups of secondary dopants were observed to play a critical role for inducing electrical characteristics of polyaniline. When secondary film doping method and p-toluenesulfonic acid were used, the electrical conductivity of the secondary doped polyaniline was measured to be increased from 0.16 to 334 S/cm. A novel vapor annealing doping method was developed to incorporate secondary dopants into solution cast polyaniline films.
LA ENSEÑANZA DE LAS CIENCIAS SOCIALES EN LA ESCUELA PRIMARIA
Authors: Pérez-Guzmán María Eugenia
Published: August 2021

El presente artículo de revisión, tiene como objetivo identificar qué se ha venido investigando sobre la enseñanza de las Ciencias Sociales en la básica primaria, a partir del rastreo de artículos de revistas derivados de investigaciones, estudios de maestría y doctorado, en países como España, México, Chile, Argentina y Colombia en los últimos cincos años. Con dicha revisión se logró concluir que los estudios sobre la enseñanza de las Ciencias Sociales están enfocados en aspectos didácticos e históricos. De ahí que es importante propender por investigaciones que busquen indagar cómo se concreta la enseñanza de las Ciencias Sociales en la escuela primaria, para tener una mirada global del objeto de estudio.
Fatores de risco odontológicos, moleculares e genéticos para o AVC: uma revisão sistemática
Authors: De Araújo Melo César Antonio , De Oliveira Morais Jullierme , Martins Gabriela de Oliveira , Costa de Araújo Souza Geórgia , De Castro Santos Pablo
Published: August 2021

Introdução. As doenças cerebrovasculares são consideradas um problema de saúde pública, dentre elas o Acidente vascular cerebral se destaca pelo seu elevado potencial de causar morbimortalidade. Objetivo. Compreender como os fatores odontológicos, moleculares e genéticos em conjunto potencializam os episódios de Acidente vascular cerebral. Método. O presente artigo foi estruturado como uma revisão sistemática da literatura e a busca dos artigos foi realizada no período de março a junho de 2020 nos portais da Biblioteca Virtual em Saúde, PubMed e nas bases de dados Scientific Electronic Library Online, ScienceDirect e SpringerLink. Resultados. Pôde-se observar a existência de associação entre a periodontite e Acidente vascular cerebral, também entre as bactérias Actinomycetemcomitans, Staphylococcus, Porphyromonas gingivalis e Streptococcus mutans causadoras de hemorragias mediadas por IL-6 e Acidente vascular cerebral. Já os ácidos graxos como ômega-3 e Ácidos Graxos Poli-Insaturados estão associados a prevenção primária e secundária da doença cardiovascular e influenciar no risco de Acidente vascular cerebral. Por fim, alguns estudos sugerem que variações e polimorfismos nos genes BRCA2 e HDAC9 estão associados a doenças cardiovasculares e cerebrovasculares. Conclusão. Destaca-se a importância da contribuição desse conhecimento em conjunto para um melhor prognóstico, segurança do paciente e assistência em saúde.