bluuebunny/crossref_metadata_2025_split huggingface dataset:
RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma
Authors: shi xinli , Li Shenghao , Wang Li , Li Hui , Li Zhen , Wang Weiyi , Bai Jing , Sun Yajing , Li Jianchun , Li Xiaoming 
Published: April 2020

Abstract
Background Interferon-inducible 16 (IFI16) /caspase-1 inflammasome activates and secretes IL-1β. However, whether the IFI16 inflammasome involved in human Laryngeal squamous cell carcinoma is still unclear. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulation the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells with DHA treatment. Hep-2 cell xenograft tumor in nude mice were used to assess the effect of DHA on laryngeal cancer. Results The study was firstly reported that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA alone or in combination with cisplatin significantly inhibited inflammasome activation and reduced IL-1β production in the xenograft tumor microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB by inhibiting USP33 expression, leading to triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Therefore, DHA depresses RalB, resulting in formation a positive feedback loop between USP33 and autophagy. Further, DHA promotes autophagy, which suppresses the IFI16/caspase-1 inflammasome activation and IL-1β production. Conclusions Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.
Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter
Authors: Campen C (Linda) MC van , Rowe Peter C , Verheugt Freek WA , Visser Frans C 
Published: April 2020

Abstract
Background most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. Therefore three measures of physical activity in ME/CFS patients, being the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) of an actometer and the %peak VO 2 of a cardiopulmonary stress test were compared. Methods female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ three months. Data of the three measures were compared by linear regression. Results in 99 female patients the three different measures were linearly, significantly and positively correlated (PFS vs Steps, PFS vs %peak VO 2 and Steps vs %peak VO 2 : all P<0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER≥1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P<0.0001), strengthening the observation of the relations between them. Despite the close correlation a large variation was observed between the three measures in individual patients. Conclusions given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies and may aid study designs aimed at improving exercise capacity.
Proficiency testing for identifying underperforming students before postgraduate education: a longitudinal study
Authors: Andreou Vasiliki , Eggermont Jan , Gielis Guy , Schoenmakers Birgitte 
Published: April 2020

Abstract
Background

Cognitive competencies are widely used to evaluate medical students’ performance in postgraduate education. However, non-cognitive competencies equally play an important role in medical students’ future career. Efficient selection of medical students in GP training plays an important role in improving healthcare quality. The aim of this study was to examine quantitatively and qualitatively the validity of a multicomponent proficiency assessment tool for identifying underperforming students in cognitive and non-cognitive competencies, prior to entering postgraduate GP education.

Design

Longitudinal cohort study with quantitative and qualitative data.

Setting

894 medical GP students from 2016 to 2018 in four Flemish universities in Belgium registered to take a multicomponent proficiency-test before admission to postgraduate education.

Method

Data on students were obtained from a proficiency-test as a test-score and from traineeship mentors’ reports qualitatively. A thematic analysis was performed to analyze mentors’ reports. The lowest and highest score quartiles were compared. The relationship between test score and whether a student was labelled as underperforming was calculated with chi-square tests, and the effect estimate was calculated with odds ratios.

Results

In total, 849 students took the multicomponent proficiency-test during 2016-2018. Test scores were normally distributed. Five different descriptive labels were extracted from mentors’ reports considering both cognitive and non-cognitive competences.

Conclusion

Students that ranked in the lowest score quartile had a higher likelihood of being signaled as underperforming than students ranking in the highest score quartile. Therefore, a low score in the multicomponent proficiency-test could indicate the need for early remediating actions. This present study did not address reliability.
Integrated regulatory-metabolic network model reveals critical mechanism and potential targets for Hepatocellular Carcinoma
Authors: Xu Yi-Zhou , Zhang Hang , Yang Qiang-Zhen , Sun Ren-Liang , Wang Ke , Shi Yong-Yong , Wang Zhuo 
Published: April 2020

Abstract
Background HCC (Hepatocellular carcinoma), the predominant form of liver cancer, has long been the top three leading cause of death in cancer worldwide. Although researchers have spent lot of effort to identify molecular targets available for treatment, the high tumor heterogeneity makes it difficult to develop effective therapy options and the drug response remains low. Under this circumstance, the precise stratification strategies are more than required. However, previous researches generally focused on single biological level, such as genome, transcriptome, or proteome, and are not able to discover effective therapeutic targets, so the systematic study of both regulation and metabolism of HCC is needed. Methods In this paper, we use two different algorithms to reconstruct regulatory networks for both HCC and normal liver cells, then integrate them with corresponding metabolic models in order to discover TFs (transcriptional factors) affecting tumorigenesis. Furthermore, a machine learning algorithm is utilized to classify HCC samples, differentially expressed genes, altered metabolic reactions and biological pathways are identified in lowest overall survival (OS) rate sub-type compared to others. Results We classify TCGA-LIHC samples into three sub-types with significantly different OS rate, and this stratification strategy is validated in another independent dataset LIRI-JP. Then, we identify 5 key TFs affecting cancer cell growth and CREB3L3 is believed to be associated with poor prognosis. The comprehensive metabolic analysis on personalized metabolic models highlight 18 metabolic genes essential for tumorigenesis in all three sub-types of patients, besides, ACADSB and CMPK1 are highly possible to be strongly correlated with lower OS. Conclusions Among 20 metabolic genes identified through metabolic analysis, 15 of them have already been targeted by approved drugs according to DrugBank. In addition, miRNAs targeting key TFs and genes are also involved in well-known cancer related pathways. The multi-scale regulatory-metabolic model reveals the critical mechanism of HCC cell proliferation and suggests potential targets.
RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells
Authors: Wu Zizhen , Liu Huifang , Sun Weilin , Du Yingxin , He Wenting , Guo Shiwei , Chen Liqiao , Zhao Zhenzhen , Wang Pengliang , Liang Han , Deng Jingyu 
Published: April 2020

Abstract
Background Ring finger protein 180 (RNF180) is an important member of the E3 ubiquitin ligase family. As a tumor suppressor gene, RNF180 is significantly associated with the prognosis of patients with gastric cancer (GC) and can inhibit the proliferation, invasion, and migration of GC cells. Signal transducer and activator of transcription 3 (STAT3) is considered one of the most common oncogenes in human cancers with a key role in GC progression. In this study, we explored the relationship between RNF180 and STAT3 in GC cells. Methods The RNF180 gene was significantly overexpressed to observe its regulatory activity on STAT3 and pSTAT3 in GC cells. We then explored the molecular signaling pathways by which RNF180 could potentially regulate STAT3 through transcriptomics and proteomics experiments. Results RNF180 overexpression could suppress STAT3 phosphorylation in GC cells. Ubiquitin label-free experiments showed that the ubiquitination level of Ras homolog gene family member C (RhoC) is significantly increased in GC cells transfected with an RNF180 expression vector (RNF180-GFP vector) compared with cells transfected with an empty vector (vehicle vector). We subsequently demonstrated that RNF180 could directly combine with RhoC and promote the ubiquitination and degradation of RhoC protein in GC cells. The phosphorylation level of STAT3 significantly decreased in GC cells after RhoC knockdown using small hairpin RNA(shRNA). Conclusions RNF180 could inhibit GC progression by reducing the phosphorylation of STAT3 via the ubiquitination and degradation of RhoC protein in GC cells. Thus, the protein may be considered a novel therapeutic target for patients with GC.
CircNOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression
Authors: Chen Shuo , Wu Wu , Li Qian-hui , Xie Bu-min , Shen Fan , Du Yu-ping , Zong Zhi-hong , Wang Li-li , Wei Xiao-qing , Zhao Yang 
Published: April 2020

Abstract
Background: Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, and could represent prognostic biomarkers and therapeutic targets. Herein, we demonstrated the role of circNOLC1 in epithelial ovarian cancer (EOC). Methods: CircNOLC1 expression was quantified in ovarian cancer tissues and normal ovarian tissues using quantitative real-time reverse transcriptase. After circNOLC1 overexpression or downregulation using a circNOLC1 overexpression plasmid or circNOLC1 short hairpin RNA (shRNA) transfection, respectively, ovarian cancer cell phenotypes and molecular mechanisms were examined in vivo and in vitro. Results: Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion, while silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced nucleolar and coiled-body phosphoprotein 1 ( NOLC1 ) mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth . Bioinformatic analysis and RNA binding protein immunoprecipitation showed that circNOLC1 could bind to epithelial splicing regulatory protein 1 (ESRP1). In addition, circ-NOLC1 overexpression significantly increased ESRP1 protein levels, and those of ras homolog family member A (RhoA) and cyclin dependent kinase 1 (CDK1); circNOLC1 downregulation had the opposite effects. The tumor-promoting effect of circNOLC1 was inhibited by knockdown of ESRP1 expression in circ-NOLC1 overexpressing cells, which might act by modulating RhoA and CDK1 expression. Conclusion: CircNOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.
Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention
Authors: Jena Atala B. , Kanungo Namrata , Nayak Vinayak , Chainy G.B.N. , Dandapat Jagneshwar 
Published: April 2020

Abstract
The recent outbreak of the coronavirus (2019n-CoV) is an unprecedented threat for human health throughout the globe. In this regards development of a suitable intervention is the need of the hour. The viral spike protein (S-Protein) and the cognate host cell receptor ACE2 can prove to be effective. Here, through computational approaches we have reported two polyphenols, Catechin and Curcumin which have dual binding affinity i.e both the molecule binds to viral S-protein and as well as ACE2. Catechin binds with S-protein and ACE2 with binding energy of -10.5 Kcal/mol and -8.9 Kcal/mol, respectively. Catechin binds with a greater affinty than that of curcumin which has a binding energy of -7.9Kcal/mol and - 7.8Kcal/mol for S-protein and ACE2, respectively. While curcumin gets bound directly to receptor binding domain (RBD) of viral S-protein, catechin binds to near proximity of RBD sequence of S-protein. Molecular simulation study demonstrates that curcumin directly binds with RBD site of S-protein during 40-100ns. In contrast, catechin binds with S-protein near the RBD site and causes fluctuation in the amino acids present in the RBD and it’s near proximity. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols, for therapeutic/preventive intervention.
Contact network analysis of patients with Novel Coronavirus Pneumonia - Based on 237 cases in Shaanxi Province
Authors: Zhangbo Yang 
Published: April 2020

Abstract
The spread of novel coronavirus is closely related to the structure of human social networks. Based on 237 cases in Shaanxi Province, using epidemiological retrospective statistics, data visualization, and social network analysis methods, this paper summarized characteristics of patients with new coronary pneumonia in Shaanxi Province, and analyzes these patients’ dynamic contact network structure. The study found that there are many clustered infections through strong ties, about one-third cases are caused by relatives' infection. In the early stages of the epidemic, it was mainly imported cases, and in the later stages, it was mainly local infection cases. The infected people were mainly middle-aged men. Symptoms of imported cases occurred on average 3 days after they arrived, and medical measures were taken on average 5 days later. All cases showed symptoms in less than 2 days on average and were then taken to medical treatment. The virus contact network can be divided into multiple disconnected components. The largest component has 12 patients. The average degree centrality in the network is 0.987. The average betweenness degree is 0. The average closeness degree is 0.452. The average PageRank index is 0.0042. The number of contacts of patients is unevenly distributed in the network.
Study on spatial distribution of pollutants and total amount reduction in the Duliujian River (Tianjin, China)
Authors: Liu Qiongqiong , Liu Dan , Zhang Yan , Wang Yanxi , Xing Meinan 
Published: April 2020

Abstract
The Duliujian River is the largest river in the downstream area of the Haihe River. In order to further clarify the main pollutant load and load contribution of the basin, and analyze the watershed pollution control unit, key pollution sources and their spatial distribution characteristics, this study divides the control unit of the basin, which is based on the digital elevation model (DEM), and applies the expansion template of Arc Map–Arc Hydro tools software. On the basis of water environment capacity and total maximum daily load (TMDL) theory, water quality standards are set in accordance with the requirements of the water body function. Considering seasonal influence and the pollution load contribution rate, a total pollution load control plan and a load optimization allocation plan are proposed, in order to realize the distribution of pollution load among point source, non-point source and safety margin. According to the calculations, TMDL of chemical oxygen demand (COD) and NH3-N in the flood season (June–September) in the Duliujian River is the largest, about 27,005 kg/d and 2,296 kg/d, respectively. During the dry season (December–March), the reduction of COD and NH3-N is the largest, reaching 50.74% and 90.14%, respectively. And Duliujian River is dominated by non-point source pollution.
Plant Extracts and Isolated Compounds Reduce Parameters of Oxidative Stress Induced by Heavy Metals: An up-to-Date Review on Animal Studies
Authors: Mirkov Ivana , Stojković Dejan , Aleksandrov Aleksandra P. , Ivanov Marija , Kostić Marina , Glamočlija Jasmina , Soković Marina 
Published: April 2020

Background:Heavy metals are elements that are naturally found in the earth. They are used in many modern-day applications in agriculture, medicine, and industry. Heavy metal poisoning occurs when the body’s soft tissues absorb too much of a particular metal. The heavy metals of interest for this review paper were cadmium, arsenic, mercury, and lead since these are the most common metals that the human body can absorb in toxic amounts. Different plant species were investigated in recent years for their effect on oxidative stress parameters after intoxication with heavy metals.Objectives:This review paper is focused on the current update to research on heavy metals induced oxidative stress in animal models and improvement of the oxidative stress parameters upon/co-/after treatment with different plant extracts and isolated compounds.Methods:The available literature was screened for the novel data regarding the influence of plant extracts and compounds on heavy metals induced oxidative stress. For that purposes Scopus database was used, looking for the publications in the last 5-10 years with the key terms: plant extracts, oxidative stress, in vivo, cadmium, lead, mercury and arcenic.Results:Various parameters of oxidative stress were investigated, and their improvement with plant extracts/ compounds was observed in the brain, lungs, kidneys, liver, uterus, testis, thymus, spleen, heart, skin and blood of experimental animals. Common parameters used to determine oxidative stress in animals were: superoxide dismutase; catalase; reduced glutathione; glutathione reductase; glutathione-S-transferase; glutathione peroxidase; lipid peroxidation; oxidized glutathione; malondialdehyde; xanthine oxidase; nonprotein-soluble thiol; thioredoxin reductase; total sulphydryl group; nitric oxide; γ-glutamyl cysteine synthetase.Conclusions:The most investigated species for antioxidant effects upon intoxication with heavy metals seem to be Allium sp., Bacopa monniera, Camellia sinensis, Moringa oleifera, Vitis vinifera and Zingiber officinale. According to literature data, the most promising effect to alleviate symptoms of intoxication was achieved with proanthocyanidins obtained from Vitis vinifera.
Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats
Authors: Li Lin-Zi , Lei Shan-Shan , Li Bo , Zhou Fu-Chen , Chen Ye-Hui , Su Jie , Lv Gui-Yuan , Chen Su-Hong 
Published: April 2020

Aim and Objective:
The Dendrobium officinalis flower (DOF) is popular in China due
to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there
have been relatively few confirmatory pharmacological experiments conducted to date. The aim of
this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent
rats, and, if so, to determine its potential mechanism of effect.

Materials and Methods:
SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg
once a day for 8 weeks. Two other groups included a healthy untreated control group and a
senescent control group. During the 7th week, a Morris water maze test was performed to assess
learning and memory. At the end of the experiment, serum and brain samples were collected to
measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide
dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the
neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine
oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using
hematoxylin-eosin (H&E) staining.

Results:
The results suggested that treatment with DOF improved learning as measured by escape
latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain.
In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx.
Histopathological analysis showed that DOF also significantly reduced structural lesions and
neurodegeneration in the hippocampus relative to untreated senescent rats.

Conclusion:
DOF alleviated brain aging and improved the spatial learning abilities in senescent
rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and
balancing the release of neurotransmitters.