bluuebunny/crossref_metadata_2025 huggingface dataset:
IncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch Schonlein purpura rats
Authors: Jiang mingyu , Dai Ji-cheng , Yin Ming-ying , Ren Ming-yong
Published: March 2021

Background: Long noncoding RNAs (lncRNAs) are important regulatory molecules in various biological and pathological processes. We herein aimed to explore whether maternally expressed gene 8 (MEG8) promotes M1 macrophage polarization in Henoch-Schonlein purpura (HSP) rats and to investigate the underlying mechanism.Methods: Relative MEG8 and miR-181a-5p expression and suppressor of SH2 domain-containing tyrosine phosphatase 2 (SHP2) RNA level were examined using quantitative reverse transcription polymerase chain reaction. Expression of SHP2 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway-related proteins was detected using western blot. Luciferase activity assay was performed to test whether miR-181a-5p could bind to MEG8 or SHP2. The macrophage phenotype was determined using flow cytometry analysis and enzyme-linked immunosorbent assay.Results: The macrophage polarization toward the M2 phenotype was observed inperipheral blood from HSP rats. Furthermore, MEG8 and SHP2 expression were down-regulated but miR-181a-5p was up-regulated in monocyte-derived macrophages from HSP rats compared with the control group. Furthermore, MEG8 acted as a sponge for miR-181a-5p to facilitate SHP2 expression. Moreover, miR-181a-5p mimic and SHP2 knockdown significantly reversed the MEG8 overexpression-mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization.Conclusion: IncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch Schonlein purpura rats.
On the Performance of Physical Layer Security in Virtual Full Duplex Non-Orthogonal Multiple Access System
Authors: Guo Weidong , Liu Yuxi
Published: March 2021

This paper investigates physical layer security analysis of cooperative non-orthogonal multiple access (NOMA) communication system. A virtual full-duplex (VFD) relaying scheme with an untrusted amplify-and-forward (AF) half-duplex (HD) relay and a trusted decode-and-forward (DF) HD relay is used in this system to improve the spectral efficiency. In order to prevent the untrusted relay from eavesdropping, a simple and practical cooperative jamming scheme is designed to confuse the untrusted relay. The exact expressions of effective secrecy throughput (EST) for NOMA users and approximate expression of EST for non-NOMA user are derived. All theoretical results are validated by numerical simulations which demonstrate that the proposed VFD-NOMA scheme is superior to existing HD-NOMA scheme in cooperative system and jamming plays an important role for obtaining acceptable EST. In addition, simulation results shows that the best secrecy performance highly depends on the system parameters such as transmit powers and jamming signal power.
Functional Display of Bioactive Peptides on the vGFP Scaffold.
Authors: Chee Sharon Min Qi , Wongsantichon Jantana , Lau Sze Yi , Sana Barindra , Frosi Yuri , Robinson Robert , Ghadessy Farid John
Published: March 2021

Grafting bioactive peptides into recipient protein scaffolds can often increase their activities by conferring enhanced stability and cellular longevity. Here, we describe use of vGFP as a novel scaffold to display peptides. vGFP comprises GFP fused to a bound high affinity Enhancer nanobody that potentiates its fluorescence. We show that peptides inserted into the linker region between GFP and the Enhancer are correctly displayed for on-target interaction, both in vitro and in live cells by pull-down, measurement of target inhibition and imaging analyses. This is further confirmed by structural studies highlighting the optimal display of a vGFP-displayed peptide bound to Mdm2, the key negative regulator of p53 that is often overexpressed in cancer. We also demonstrate a potential biosensing application of the vGFP scaffold by showing target-dependent modulation of intrinsic fluorescence. vGFP is relatively thermostable, well-expressed and inherently fluorescent. These properties make it a useful scaffold to add to the existing tool box for displaying peptides that can disrupt clinically relevant protein-protein interactions.
Determination of Physiological Traits contributing to Drought Tolerance and Heritability of Sorghum Genotypes
Authors: Mwamahonje Andekelile , Eleblu John , Ofori Kwadwo , Feyissa Tileye , Deshpande Santosh , Tongoona Pangirayi
Published: March 2021

The authors have requested that this preprint be removed from Research Square.
Mapping QTL Associated with Partial Resistance to Aphanomyces Root rot in Pea (Pisum Sativum L.) using a 13.2K SNP Array and SSR Markers
Authors: Wu Longfei , Fredua-Agyeman Rudolph , Hwang Sheau-Fang , Chang Kan-Fa , Conner Robert , McLaren Debra , Strelkov Stephen E.
Published: March 2021

Aphanomyces root rot (ARR), caused by Aphanomyces euteiches Drechs., is a destructive soilborne disease of field pea (Pisum Sativum L.). No completely resistant pea germplasm is available, and current ARR management strategies rely on partial resistance and fungicidal seed treatments. In this study, an F8 recombinant inbred line (RIL) population of 135 individuals from the cross ‘Reward’ (susceptible) × ‘00-2067’ (tolerant) was evaluated for reaction to ARR under greenhouse conditions with the A. euteiches isolate Ae-MDCR1 and over 2 years in a field nursery in Morden, Manitoba. Root rot severity, foliar weight, plant vigor and height were used as estimates of tolerance to ARR. Genotyping was conducted with a 13.2K single-nucleotide polymorphism (SNP) array and 222 simple sequence repeat (SSR) markers. Statistical analyses of the phenotypic data indicated significant (P<0.001) genotypic effects and significant G×E interactions (P<0.05) in all experiments. After filtering, 3050 (23.1%) of the SNP and 30 (13.5%) of the SSR markers were retained for linkage analysis, which distributed 2999 (2978 SNP + 21 SSR) of the markers onto nine linkage groups representing the seven chromosomes of pea. Mapping of quantitative trait loci (QTL) identified 5 major-effect (R2 > 20%), 13 moderate-effect (10%<R2< 20%) effect and 10 minor-effect (R2 <10%) QTL. A genomic region on chromosome IV, delimited by the SNP markers PsCam037549_22628_1642 and PsCam026054_14999_2864, was identified as the most consistent region responsible for partial resistance to A. euteiches isolate Ae-MDCR1. Other genomic regions important for resistance were of the order chromosome III, II and VII.
Retinal Vein Occlusion: A Form of Local Venous Thrombosis or a Result of Systemic Endothelial Dysfunction
Authors: Bozkurt Erdinç , Cetin Turkhun , Rencuzogulları Ibrahim
Published: March 2021

Background: To determine the condition of systemic endothelial function and carotid intima media thickness (CIMT) in patients with retinal vein occlusion (RVO) and to identify the risk factors associated with the disease.Methods: Seventy-six patients who presented to the clinic with the diagnosis of RVO and 76 age- and gender-matched healthy individuals without a RVO history were included in the study. The patients' vision levels and central macular thickness were measures, and diabetes, hypertension, hyperlipidemia, carotid artery disease, body mass index and smoking histories were recorded. The endothelial function levels of the patients, pulse wave velocity (PWV), and CIMT were measured. Serum hematological parameters were evaluated.Results: The most important risk factor in patients with RVO was found to be hypertension (OR 1.455, 95% CI 1.981-9.272; p=0.001) compared to the control group, and diabetes (OR 0.460, 95% CI 1.981-9.272; p=0.001) and hyperlipidemia (OR 0.124, 95% CI 0.371-3.456; p=0.828) were significantly more common among the patients.There was a statistically significant difference between the RVO and control groups in terms of flow-mediated dilation (OR 0.050, 95% CI 0.020-0.080; p =0.001), PWV (OR 0.392, 95% CI 0.271-0.513; p<0.001), and the CIMT of both sides (OR 2.434, 95% CI 1.801-3.055 for the right CIMT and OR 2.284, 95% CI 1.646-2.922 for the left CIMT) (p<0.001 for all).Conclusion: Considering that RVO is associated with systemic endothelial dysfunction and may also be accompanied by carotid artery stenosis, we think that additional systemic diseases should be questioned in this patient group.
Improving the uneven distribution of the health workforce worldwide: a perspective from the pharmacy workforce.
Authors: Mamiya Kayoko Takeda , Bates Ian , John Christopher , Bader Lina , Alnahar Saja A.
Published: March 2021

Background

The World Health Organization (WHO) currently estimates a shortage of approximately 18 million health workers worldwide, potentially impacting the achievement of the United Nations (UN) Sustainable Development Goal on health. One of these goals is to stimulate and guide the creation of at least 40 million new jobs in the health and social sectors and reduce the projected shortage of 18 million health workers, primarily in low- and lower-middle-income countries, by 2030. However, since 2006, there have been few surveys conducted of internationally trained pharmacists worldwide, while surveys of internationally trained nurses and doctors are being conducted by the OECD, WHO and World Bank Group.
Methods

A global survey on intention to migrate was conducted through International Pharmacy Students’ Federation (IPSF), Young Pharmacists Group (YPG) at International Pharmaceutical Federation (FIP) members. The questionnaire was distributed via email with a cover letter to all IPSF and YPG members with a survey URL.
Results

This study showed some differences in “intention to migrate”, “the motivation to migrate”, “the length of stay in the host country”, “the satisfaction with initial pharmacy education, home country and home country pharmacists’ work” among the income levels as defined by the World Bank classification.
Conclusion

To improve the uneven distribution of pharmacists, an education system that connects initial pharmacy education and lifelong education might need to be created or altered to address the role of pharmacists in each country. To that end, we need to share knowledge and practices related the development and implementation of lifelong learning systems and the role of pharmacists in various countries worldwide through studies and the work of international organizations.
A 2D porous Pb-MOF based on 2-nitroimidazole: CO2 adsorption, electronic structure and luminescence
Authors: Li Xiu-Yuan , Ying-Bo Wang , Yan Song , Dan Xiang , He Chaozheng
Published: March 2021

A new porous metal-organic framework, [Pb5(Ac)7(nIm)3]n (1), has been successfully synthesized by employing 2-nitroimidazole ligand and Pb2+ ion. 1 contains novel the ribbon-shaped Pb-O SBU and reveals a 2D porous framework with a 1D tubular channel. Moreover, 1 shows moderate adsorption uptake towards CO2 and luminescence properties from intraligand charge transfer. We further confirmed nitro group and metal ion are important adsorption sites by GCMC simulations, and the electronic structures of 1 was investigated.
Protective effect of hydrogen against ischemia-reperfusion induced spinal nerve cell apoptosis
Authors: Sun Yanqing , Shi Wei , Yuan Bo , Wang Zhiwei , Zhou Shengyuan , Zhao Yin , Chen Xiongsheng
Published: March 2021

Background: This study aims to explore the protective effect of hydrogen against oxygen-glucose-serum deprivation/restoration (OGSD/R)-induced PC12 cell apoptosis in vitro and the possible underlying mechanism. Methods: A normal control (NC) group was set where PC12 cells were cultured normal, while a positive control (PC) group, where PC12 cells were exposed to OGSD 12h/R1h without intervention, and a hydrogen intervention (HI) group, where PC12 cells were exposed to OGSD 12h/R1h plus HI, were conducted at the same time. At OGSD 12h/R 1h, cells were DAPI stained to detect viability and changes in the expression of apoptosis-associated proteins caspase-3, caspase-12 and CHOP/GADD153, and the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4. At the same time, the effect of HI was observed. Results: The result revealed that compared with NC group, cell apoptosis was more severe and cell viability was reduced significantly in PC group, while cell apoptosis was ameliorated and cell viability was increased significantly in HI as compared with PC group. In addition, the content of caspase-3 and caspase-12 in HI group was decreased significantly as compared with that in PC group. During this process, the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4 was activated. In HI group, the expression of this protein was decreased and cell viability was increased significantly as compared with those in PC group. Conclusions: Hydrogen was able to inhibit OGSD/R-induced PC12 cell apoptosis and exert a protective effect against ischemia-repurfusion injury (IRI) to nerve cells, probably through inhibiting the endoplasmic reticulum-related signaling pathway protein.
Effect of Co2+ Doped Seed Layer on Morphology and Photoelectric Properties of ZnO Nanoarray
Authors: Li lihua , Shi Qingkui , Hou Bingyang , Ning Xiangmei , Li Qian , Kim Bok-Hee , Huang Jinliang
Published: March 2021

ZnO nanoarray were synthesized by hydrothermal method on Co2+-doped Zn1-xCoxO (x（mol%）=0.00, 0.01, 0.02, 0.03, 0.04, 0.05) seed layers pre-coated on ITO substrate. The effects of different Co2+ doping concentrations on morphology and photoelectric properties of ZnO nanoarray including transient photo-current and charge transfer resistance were investigated. The addition of Co2+ in the seed layer could perfect the oriented growth of ZnO nanoarray and apparently enhance its photo current. FESEM observation confirmed that the ZnO nanoarray were grown in the way perpendicular to ITO substrate along the direction of (002). Meanwhile, UV-vis tests shown that the band gap energy was decreased from 3.37 eV to 3.16 eV due to Co2+ doping and the ZnO nanoarray had a strong visible region in the range 400-650 nm. The transient photo-current was found to vary from 0.005 to 0.15 mA/cm2 under AM 1.5G simulated sunlight illumination. Photoelectric properties was correlated with the recombination of photo-generated charge carriers, which was inhibited with optimal Co2+ doping concentrations and was beneficial for application in perovskite solar cells.
Extracting Disease-Specific Clinical Experiences from Ancient Literature of Traditional Chinese Medicine with Deep Learning
Authors: Lu Yongmei , Chen Li , Zhang Tingting , Bu Lingmei , Ye Ying , Yu Zhonghua , Wang Hao
Published: March 2021

Background: Ancient literature of Traditional Chinese Medicine (TCM) contains massive clinical experiences which are important ingredient of TCM knowledge and valuable for TCM clinical practice of nowadays. However, it is difficult for TCM professionals to acquire such valuable experiences due to their massive volume and broad occurrence in the literature. Furthermore, different characteristics of ancient Chinese language from the modern one lead to additional challenges for analyzing the literature, regardless of how to perform the analyzing, manually or automatically with a software toolkit. Methods: In order to overcome the aforementioned challenges, we formalize a novel information extraction task for ancient literature of TCM, and the entities to be extracted are Disease-Specific Clinical Experiences (DSCEs) occurring in the literature. For the purpose, we have collected two corpora from ancient literature of TCM and annotated them manually with DSCEs occurrence information for the diseases pregnant abdominalgia and colporrhagia (妊娠腹痛及下血) and jaundice (黄疸) respectively. We further propose a deep learning and CRF-based algorithmic framework with character encoding of ancient Chinese, thus avoiding the special difficulty in word segmentation for ancient Chinese texts. We investigate the framework with different methods for contextual encoding of characters in a sentence, including CNN, Bi-LSTM and BERT, and diverse approaches to aggregate contextual information of characters into a sentence encoding, such as max-pooling and attention mechanism. After that all the encoded sentences in a section of the literature are passed through a Bi-LSTM-based sequence labelling model with CRF inference on its top to obtain an optimal label sequence for the sentences in the section. Results: We conduct a series of experiments on the two corpora to verify the effectiveness of our framework for the task, and evaluate its effectiveness with different metrics in two granularities of labelling, namely accuracy/F1-value in sentence-level labelling and precision/recall/F1-value in correct recognition of the whole DSCEs. Conclusion: The experimental results demonstrate that the deep learning and CRF-based framework with character encoding of ancient Chinese could achieve an accuracy of 80.40%±1.64% and an F1-value of 76.73%±1.59% for the sentence labelling, while for recognition of the whole DSCEs, it is able to obtain the recall of 44.97%±2.16% and the precision of 51.13%±2.64%, meaning that the framework is a promising baseline for further development of the novel information extraction task for TCM.
Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3 Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease
Authors: Ahmed Sahabuddin , Panda Samir Ranjan , Kwatra Mohit , Sahu Bidya Dhar , Naidu VGM
Published: March 2021

Several activators of NLRP3 inflammasome have been described; however, the central mechanisms of NLRP3 inflammasome activation in brain microglia, especially at the activating step through free radical generation, still require further clarification. Hence the present study aimed to investigate the role of free radicals in activating NLRP3 inflammasome driven neurodegeneration and elucidated the neuroprotective role of perillyl alcohol (PA) in vitro and in vivo models of Parkinson’s disease. Initial priming of microglial cells with lipopolysaccharide (LPS) following treatment with hydrogen peroxide (H2O2) induces NF-κB translocation to nucleus with robust generation of free radicals that act as Signal 2 in augmenting NLRP3 inflammasome assembly and its downstream targets. PA treatment suppresses nuclear translocation of NF-κB and maintains cellular redox homeostasis in microglia that limits NLRP3 inflammasome activation along with processing active caspase-1, IL-1β and IL-18. To further correlates the in vitro study with in vivo MPTP model, treatment with PA also inhibits the nuclear translocation of NF-κB and downregulates the NLRP3 inflammasome activation. PA administration upregulates various antioxidant enzymes levels and restored the level of dopamine and other neurotransmitters in the striatum of the mice brain with improved behavioural activities. Additionally, treatment with Mito-TEMPO (a mitochondrial ROS inhibitor) was also seen to inhibit NLRP3 inflammasome and rescue dopaminergic neuron loss in the mice brain. Therefore, we conclude that NLRP3 inflammasome activation requires a signal from damaged mitochondria for its activation. Further pharmacological scavenging of free radicals restricts microglia activation and simultaneously supports neuronal survival via targeting NLRP3 inflammasome pathway in Parkinson’s disease.
Psychological Effects on Healthcare Workers in Syria During COVID-19
Authors: Alhaffar MHD Bahaa Aldin , Alhaffar MHD Alaa Aldin , Kouchaji Chaza , Alsuliman Tamim
Published: March 2021

Introduction:Since the declaration of COVID-19 as a global pandemic, there has been a dramatic increase in the number of infected cases. Thus, the number of hospital admissions has peaked during a short period, which in return has created a huge burden on healthcare workers. The effect of this pandemic on HCWs can be more severe in war-torn countries. This research aims to explore the psychological effects of the current pandemic on healthcare providers in Syria and compare it with the situation of Syrian HCP outside Syria.Materials and methods:660 has participated in this cross-sectional study using an online questionnaire during two phases (two months apart). The first sample included 76 participants which were used for comparison only, and the second sample consisted of 584 participants (118 outside Syria, 466 inside Syria). The study included demographic, social, and workplace-related questions, as well as three scoring systems including The Pittsburgh, Sleep quality index (PSQI), Kessler Psychological Distress Scale (K10), and Generalized Anxiety Disorder (GAD 7).Results: 72.4% of the first sample had poor sleep quality compared to 80% for the second sample, while over 40% of the first sample had scored well on the Kessler scale and 17% scored severe stress disorder, the second sample scored 29.8% and 27.9% on the same index retrospectively. Over 70% of the two samples scored mild on the generalized stress disorder index. Both inside and outside Syria samples had very similar results on the three indices, and no significant difference was noticed between the sample inside Syria and the sample outside Syria for the Pittsburgh Sleep Quality Index (P=0.900), and for the Generalized Anxiety Disorder score (P=0.798), and no significant difference was noticed between the two samples for the Kessler Psychological Distress Scale (P=0.231). Conclusion: The current pandemic has imposed new concerns related to the preparedness of health systems worldwide but especially in countries with limited resources. Additionally, addressing mental health issues has become vital to ensure that healthcare systems are more effective.Regions of low income and those suffering from armed conflict may benefit from the conclusions of this study to ameliorate the medical practice conditions in the setting of such pandemics as COVID-19.
Lithium Prevents Telomere Shortening in Cortical Neurons in Amyloid-Beta Induced Toxicity
Authors: Themoteo Rafael Martins , de Paula Vanessa , Kimberly Nikole , Brentani Helena , Forlenza Orestes Vicente
Published: March 2021

BackgroundThere is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. MethodsCortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2mM, 0.2mM and 0.02mM) for seven days. Amyloid toxicity was induced 24 hours before the end of lithium treatment. ResultsLithium resulted in 120% (2mM), 180% (0.2mM) and 140% (0.02mM) increments in telomere length as compared to untreated controls. Incubation with Aβ1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. ConclusionsLithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils.
Sceptic priors and climate consensus
Authors: McDermott Grant
Published: March 2021

How much evidence would it take to convince sceptics that they are wrong about climate change? I explore this question within a Bayesian framework. I consider a group of stylised sceptics and examine how these individuals update their beliefs in the face of current and continuing climate change. I find that available evidence in the form of instrumental climate data tends to overwhelm all but the most extreme priors. Most sceptics form up dated beliefs about climate sensitivity that correspond closely to estimates from the scientific literature. However, belief convergence is a non-linear function of prior strength. It thus becomes increasingly difficult to convince the remaining pool of sceptics. I discuss necessary conditions for consensus formation under Bayesian learning and show how apparent deviations from the Bayesian ideal still be accommodated within the same conceptual framework. I argue that a generalized Bayesian model thus provides a bridge between competing theories of climate scepticism as a social phenomenon.
Performance Measurement for New Mobile Data Services During Generation Upgrading Period: A Case of China's Telecom Industry
Authors: Du Yu , Zhang Xiaohang , Li Zhengren , Guo Yijun
Published: March 2021

For the global telecom operators, mobile data services have gradually taken the part of traditional voice services to become the main revenue growth point. However, during the upgrading period of new generation networks (Such as 5G), new mobile data services are still at the stage of exploration, the network capabilities and the application scenarios are unmatured. In this phase, it is incomplete and misleading to simply measure the performance of new services from one dimension, such as data traffic or revenue, and the measurement should be dynamically changed according to the development of the new services. Therefore, telecom operators want to improve the existing performance measurement from the aspect of integrity and dynamics. In this paper, we propose Mobile-data-service Development Index (MDDI), and build a quantitative model to dynamic measure the overall performance of mobile data services. To approach a fuller understanding, we creatively bring investment indicators and networks reliability indicators into performance indicators system, and discuss the relationships among subindices and the selection of outcome criteria in MDDI. In the part of empirical research, we use the model to analyze the dynamic characteristics of a new mobile data service in China, and summarize the development strategies of every stage. The findings can also give guidelines for new services of 5G and other new generation networks in the future.
Study on the Relationship Between Myocardial Microcirculation Perfusion and Electrocardiogram ST Segment Depression in Patients With Hypertrophic Cardiomyopathy
Authors: Guan Lina , Yuan Chao , Mu Yuming , Abdullah Guri Qiman Hoga
Published: March 2021

Objective: To investigate the correlation between myocardial microcirculation perfusion status and the ST-segment depression(STD) in patients with hypertrophic cardiomyopathy (HCM)Method: Myocardial microcirculation perfusion of 32 patients with HCM (HCM group) and 28 healthy volunteers (control group) were examined using MCE, and the parameters including peak intensity (PI), area under the curve (AUC), rising slope (RS), and the time to peak (TTP) were analyzed. All subjects were examined by electrocardiogram, and the amplitude of downward movement of ST segment was measured. Then patients were divided into 3 groups according to the degree of downward movement of ST segment: ST1 group (0<ST≤0.1 MV); ST2 group (0.1 MV<ST≤0.2MV); ST3 group (0.2< MV<ST≤0.3 MV). At last, the relationship between myocardial microcirculation disorder and the degree of ST segment depression was explored.Results: Patents with HCM exhibit lower PI and AUC than their healthy counterparts (P < 0.001). No significant difference was found in RS and TTP between two groups (P > 0.05). ST depression was found in all the patients in the HCM group (P < 0.001). There was no significant linear correlation between PI and the degree of ST segment depression (r = -0.348). Then PI value was compared among ST1, ST2, ST3 and control group. The results showed that the PI value in both ST1 group and ST2 group differs from ST3 group (P < 0.01), while there was no significant difference between ST1 and ST2 group (P < 0.05). Conclusion: When ST depressed more than 0.20 mV, the STD is related to the decrease of microcirculation perfusion in hypertrophic myocardium.
Potential Diagnostic Value of Circulating miR-1183 and CHURC1 Biomarkers in Early-Onset Preeclampsia
Authors: Altındirek Didem , Gunel Tuba , Benian Ali , Aydınlı Kılıç
Published: March 2021

BackgroundPreeclampsia (PE) is a multi-systemic disease of pregnancy and leading cause of maternal and fetal mortality and morbidity worldwide. The differential expression of circulating microRNAs (miRs) were reported in maternal plasma of pregnant women and they could be stabilized in plasma. The aim of this study was to characterize the molecular mechanism of PE development through miR-1183.Methods and ResultsPlasma samples were obtained between 26 and 32 weeks of gestation from early-onset PE cases (n=31) and women with normotensive pregnancies (controls, n=22). The expressions of miR-1183 and Churchill containing domain 1 (CHURC1) were measured in maternal plasma. CHURC1 3’ untranslated region was determined as the target of miR-1183 using in silico analysis. miR-1183 and CHURC1 expression levels were assessed by real-time polymerase chain reaction (RT-PCR). An inverse correlation was found between circulating miR-1183 and CHURC1 expression levels with, miR-1183 up-regulated (p=0.002) and CHURC1 down-regulated (p<0.001) in maternal plasma of preeclamptic women compared to controls. The accuracy of levels of miR-1183 and CHURC1 according to area under receiver operating curve (ROC) analysis were characteristic curve analysis: the area under the curve (AUC) were: 0.79; (CI: 0.62-0.91) and 0.96; (CI: 0.78-0.99), respectively.ConclusionThese findings not only characterize a new mechanism for the disease, but also provide potential therapeutic targets.
Curcumin Induces MCF-7 Cells Pyroptosis Via Autophagy/CTSB/NLRP3/Caspase-1/GSDMD Signaling Pathway In Vitro And Vivo
Authors: Duan Haonan , Jiang Liping , Sun Xiance , Liu Xiaofang , Yang Guang , Sun Xianzhi , Cheng Tingting , Ji Yuchen , Zhang Fan , Du Yue , Ou Shu , Ma Rufei , Guan Xiuliang , Teng Nan , Li xiaofeng
Published: March 2021

Background: Curcumin, as a lipid-lowering drug, has been reported to be effective in the treatment of breast cancer. However, the underlying molecular mechanisms have not been completely investigated. Methods: MTT assay was used to determine the effect of curcumin on survival rate of MCF-7 cells. The effects of curcumin on tumor growth were observed in animal models of breast cancer. The positive reactions of Caspase-1, IL-1β and IL-18 were detected by immunohistochemistry. LC3, p62, CTSB, ASC, Pro-Caspase-1, GSDMD, NLRP3, Caspase-1, GSDMD-N, IL-1β and IL-18 were determined by Western blot in vitro and vivo. The release of extracellular IL-1β and IL-18 was determined by ELISA. LDH release was measured. The expression level of CTSB in cytoplasm were determined by immunofluorescence assay. Cell proliferation, cell migration and tube formation assays were used to determine the abilities of cells. In this study, NLRP3 inflammasome inhibitor MCC950, cathepsin B inhibitor CA-074 ME and autophagy inhibitor 3-MA were used to act on cells to investigate the role of NLRP3 inflammasome, cathepsin B and autophagy in curcumin-induced pyroptosis of MCF-7 breast cancer cells.Results: In mouse model of breast cancer, we observed that curcumin treatment significantly induced cell autophagy and pyroptosis. In human breast cancer MCF-7 cells, we found that curcumin induced pyroptotic cell death was dependent on the activation of NLRP3/Caspase-1/GSDMD signaling pathway, which was CTSB-dependent. In addition, curcumin-induced cell autophagy caused lysosomal rupture and CTSB release. Furthermore, NLRP3 inhibitor (MCC950) significantly suppressed curcumin-induced pyroptosis, as well as CTSB inhibitor (CA074 Me) and autophagy inhibitor (3-MA). Besides, we also found that curcumin suppressed cell proliferation, cell migration and tube formation, which could be reversed by inhibitors. Conclusions: In summary, our results demonstrated that curcumin induced MCF-7 cell pyroptosis by the activation of autophagy/CTSB/NLRP3/Caspase-1/GSDMD signaling pathway. These findings offer novel insights into the potential molecular mechanisms of curcumin in treatment of breast cancer.
Longitudinal Associations Between TPO Gene Variants and TPOAb Seroconversion in a Population Based Study: Tehran Thyroid Study (TTS)
Authors: Ghanooni Amir Hossein , Zadeh-Vakili Azita , Rezvankhah Boshra , Nodushan Somayeh Jafary , Akbarzadeh Mahdi , Amouzegar Atieh , Daneshpoor Maryam Sadat , Khalili Davood , Mehrabi Yadollah , Sarvghadi Farzaneh , Ebadi Seyed Alireza , Azizi Fereidoun
Published: March 2021

Background: Autoimmune thyroid diseases are among the most common autoimmune diseases in the world. They are usually accompanied by the presence of anti-thyroid antibodies as the early predictive marker. Genetic determinants of the susceptibility to develop thyroid antibodies are still poorly understood. This study aimed to investigate the relation between thyroid peroxidase (TPO) gene variants (53 SNPs) and positive TPOAb and also to evaluate the effect of some environmental factors on changes from negative to positive TPOAb (Seroconversion). Methods: Participants from the Tehran Thyroid Study (TTS) in phases 1 and 2 (N=5317, ≥ 20 years) were evaluated for the positive TPOAb and its relationship with 53 SNPs from TPO gene (a cross-sectional approach). At the second stage of the study (a longitudinal approach), negative TPOAb participants (control group, N= 4815) were followed up for about 5.5 (5.54±1.62) years until they have had positive results for TPOAb (“TPOAb seroconversion”). The association between TPO gene polymorphisms and TPOAb seroconversion was evaluated using logistic regression analysis and SKAT package (sequence kernel association test). Results: In cross-sectional analyses, 17 SNPs were associated with TPOAb positivity (521 positive TPOAb participants) after the adjustment for age, sex, body mass index (BMI), smoking, the number of parity and oral contraceptive consumption (P <0.05). In longitudinal analyses, there was an association between TPOAb seroconversion and four SNPs before, and three SNPs after adjustment (P <0.05). Conclusions: TPOAb seroconversion could be affected by some thyroid peroxidase gene variants.
Breast Cancer Risk factors in Relation to Molecular Subtypes in Breast Cancer Patients from Kenya.
Authors: Sayed Shahin , Fan Shaoqi , Moloo Zahir , Wasike Ronald , Bird Peter , Saleh Mansoor , Shaikh Asim Jamal , Figueroa Jonine , Naidoo Richard , Makokha Francis , Gardner Kevin , Oigara Raymond , Njoroge Faith Wambui , Magangane Pumza , Mutebi Miriam , Chauhan Rajendra , Mwanzi Sitna , Govender Dhirendra , Yang Xiaohong Rose
Published: March 2021

BackgroundFew studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. MethodsWe conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.ResultsThe median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3 and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and Triple Negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER positive tumors, ER negative patients were more likely to have higher parity (OR=2.03, 95% CI= (1.11, 3.72), p=0.021, comparing ≥5 to <2 children) and younger age at first pregnancy (ORtrend=0.77, 95% CItrend=0.61, 0.98, Ptrend=0.032, comparing older to younger age). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR=0.45, 95% CI= 0.23, 0.87, p=0.018, comparing ≥5 to <2 children); HER2-enriched patients were less likely to be obese (OR=0.36, 95% CI=0.16, 0.81, p=0.013) or older age at menopause (OR=0.38, 95% CI=0.15, 0.997, p=0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies are needed to develop population and subtype specific risk prediction/prevention strategies.
The association between serum sodium levels and tuberculous meningitis compared to viral and bacterial meningitis: Multicenter retrospective cohort study
Authors: Na Seunghee , Kim Taewon , Song In-Uk , Chung Sung-Woo , Kim Seong-Hoon , Oh Yoon-Sang , Oh Juhee , Kim Woojun
Published: March 2021

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) in hopes of providing additional information for the differential diagnosis of TBM from other types of infectious meningitis, especially from viral meningitis (VM). Cross-sectional and longitudinal data involving 5,026 participants more than 18 years of age were analyzed in the total population and the propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, VM, and bacterial meningitis (BM) patients were compared. The initial serum sodium levels were significantly lower in the TBM patients than in the VM and BM patients (136.9 ± 5.9 vs. 139.0 ± 3.1, p < 0.001 for TBM vs. VM, and 138.3 ± 4.7 mmol/L and p < 0.001 for TBM vs. BM) and it dropped significantly more steeply to lower levels in both the TBM and BM patients compared to the VM patients. Consequently, the lowest serum sodium levels were in the order of the TBM < BM < VM patients, which were also statistically significant in all subgroups. (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). The participants with lower serum sodium levels were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium levels than the initial sodium levels (OR 8.4 (95% CI: 4.5–15.8, p < 0.001)). The baseline and longitudinal evaluation of serum sodium levels can provide supportive information for the differential diagnosis of TBM from VM or BM.
Based on Network Pharmacology and Bioinformatics to Explore the Mechanism of Bazhen Decoction in the Treatment of Clear-Cell Renal Cell Carcinoma
Authors: Liu Yu , Li Mingquan , Teh LaiKuan , zhao Liangbin , Ye Naijing
Published: March 2021

Objective: To explore the mechanism of Bazhen Decoction in the treatment of Clear-cell renal cell carcinomaCRCC）through the methods of network pharmacology and bioinformatics.Methods: The active ingredients of Bazhen decoction were identified through TCMSP, Targets of each active ingredients were accessed through TCMSP and Swiss Target Prediction. The target gene by CRCC was obtained from GEO database and interlinked of both active ingredient and cancer gene was performed to obtain drug-disease protein target gene. Cytoscape 3.7.1 software was used to draw the active ingredient-target network. The protein interaction network was drawn using the String database and Cytoscape 3.7.1 software. Gene Ontology (GO) and KEGG pathway analysis on the target were performed using R language.Results: From analysis, 160 of active ingredients were found from Bazhen Decoction with 5002 of predicted targets; 544 of disease targets and 39 drug-disease protein target genes.Network analysis on drug-disease protein interaction found out the targets were mainly involve mechanisms such as positive regulation of angiogenesis, positive regulation of vasculature development, epithelial cell proliferation,growth factor receptor and growth factor binding activity, as well as prostanoid receptor binding activity. Treatment of clear-cell renal cell carcinoma can be controlled through regulating the signaling pathways in relation to bladder cancer, MicroRNAs in cancer, focal adhesion, Human cytomegalovirus infection, Ovarian steroidogenesis and HIF-1 signaling pathway.Conclusion: The mechanism of Bazhen Decoction in the treatment of CRCC reflects the characteristics of multiple ingredients, multiple targets, and multiple pathways of traditional Chinese medicine. The findings from this study able to provide a theoretical basis on anti-cancer mechanism.
A Comprehensive Study on Prediction Reliability of The Severity of Computed Tomography Involvement in Patients with Covid-19
Authors: Kalkan Semih , Gurler Volkan , Guner AHMET , Kalcik Macit , Kasali Kamber , Keten Mustafa Ferhat , Tonkaz Gokhan , Bayam Emrah , Karaduman Ahmet , Ozkan Mehmet
Published: March 2021

Purpose: Computed tomography (CT) emerges as a high–sensitivity tool in diagnosing SARS-CoV-2 virus on admission, even with the cases of negative reverse transcription polymerase chain reaction (RT-PCR). Moreover, CT plays a significant role in the evaluation of disease severity. In this study, we aimed to identify several parameters that could aid in evaluating the initial chest CT severity score (CT-SS).Methods: A total of 348 RT-PCR positive patients were divided into three groups by evaluating the chest CT severity score (CT-SS) in detail. These three groups were defined as the CT-SS obtained 0-7, 8-15, 16-40 classified as mild, moderate and severe involvement, respectively. Patients with end-stage malignancy or immunodeficiency were excluded from the study. All CT images were evaluated by two chest radiologists, unaware of the clinical data.Results: The analysis of categorical variables show that the chest CT-SS tends to increase with higher CHA2DS2VASC risk score (RS) (p= 0.001), M-CHA2DS2VASC RS (p = 0.001), and CHADS2 RS (p = 0.003). Moreover, age, hypertension, cardiothoracic ratio, aortic diameter, white blood cell count, neutrophil counts, neutrophil-lymphocyte ratio, c-reactive protein, D-dimer, ferritin, fibrinogen, blood urea nitrogen, and lactate dehydrogenase were also found to be associated with higher chest CT-SS. A 5-variable multivariable linear regression model, consisting of more frequently used variables, suggests a higher CHA2DS2VASC RS as the only statistically significant variable predicting a higher severity scoreConclusion: The CHA2DS2VASC RS may assist clinicians in predicting the CT-SS in COVID-19 patients, even if they are asymptomatic.
Physical activity is associated with disease severity in idiopathic pulmonary fibrosis: a cross-sectional study
Authors: Prasad Jyotika Devi , Holland Anne E , Glaspole Ian N , Westall Glen P
Published: March 2021

BackgroundPhysical inactivity is associated with poor outcomes in patients with many chronic lung diseases, however little is known about physical activity in patients with idiopathic pulmonary fibrosis (IPF). Our aim was to describe daily physical activity (DPA) in patients with a confirmed diagnosis of IPF and analyse its associations with traditional markers of disease severity and quality of life.MethodsFifty-nine patients with IPF had DPA parameters and sedentary time assessed with the Sensewear armband for seven consecutive days. Participants completed the Hospital Anxiety and Depression scale (HADS), St Georges Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). Data on current markers of disease severity; forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO) and 6-minute walk test (6MWT) as well as prognostic markers; composite physiologic index (CPI) and gender age and physiology (GAP) was collected.ResultsPatients had a median daily step count of 3957 (300–7614), mean daily moderate to vigorous (MV) physical activity duration of 8.6 minutes (-13.1 to 30.3) and mean total daily sedentary time of 1234.6 minutes (± 122.8). Patients with early stages of IPF according to GAP stage had significantly higher daily step count than those with more severe disease (p < 0.003). Age, BMI and DLCO accounted for 54% variability in physical activity duration. The 6-minute walk distance and DLCO accounted for 44% variability in daily step count. Patient reported outcomes had weak association with daily step count and MV physical activity duration.ConclusionIn IPF, increasing disease severity is associated with reduced DPA. DPA may be a meaningful outcome for future trials of therapies designed to enhance patient functioning and wellbeing.Trial Registration: please note that a request has been made for retrospective registration with the Australian New Zealand Clinical Trial Registry with the request number being 381161. Due to holiday period closure, this is yet to be processed. I will supply this as soon as accepted.
Dexmedetomidine reduced isoflurane neurotoxicity by preventing cytoskeletal depolymerization via the BDNF/RhoA signal pathway
Authors: Chi Liang , Yao Xiaoyang , Gao Caixia , Dong Huansheng , Liu huanqi
Published: March 2021

Background

Dexmedetomidine (Dex) has a significant neuroprotective effect in isoflurane-induced neurotoxicity during the critical period of synaptogenesis. However, the mechanisms by which Dex protects developing neurons are not clear. This research evaluated the protective effect of Dex against neuronal damage induced by isoflurane using a mouse model.
Methods

Neonatal Swiss mice at postnatal day 7 (PND7) were injected intraperitoneally with 15µg/kg, 20µg/kg, or 25µg/kg Dex, or normal saline, and then treated with 2% isoflurane for 2h. The results showed that 20µg/kg Dex could reduce isoflurane-induced neurocognitive deficits as assessed using the Morris water maze. The mechanisms by which Dex protected neurons were investigated using hippocampal neurons isolated from PND4-7 mice and exposed to 2% isoflurane (2h). Dex prevented cytoskeletal depolymerization that was induced by isoflurane.
Results

15µg/ml Dex significantly reduced the percentage of apoptotic neurons. Dex reduced expression of activated caspase-3 in neurons compared to isoflurane only exposed mice. Using primary cell cultures from neonatal mouse hippocampi, we determined that dexmedetomidine could reverse isoflurane-induced RhoA (a small
A Path Analysis Model for Explaining Factors That Influence the Use of Masker among Commuting Workers Using KRL Commuter Line Bogor Jakarta
Authors: Kusmawan David , Andari Shofi , S Indri Hapsari
Published: March 2021

Jakarta is one of the most air polluted cities in the world, it can increase the risk of healthy of commuting worker. As one of the most air polluted cities in the world, Jakarta is at high risk of its commuting worker’s health. They are at risk of being exposed to pollutant. This study aims to determine the factors influencing directly and indirectly to healthy behavior (using masker) for commuting workers who use the KRL Commuterline Bogor - Jakarta. A total of 155 respondents participated in the study and the collected data were then analyzed using descriptive and path analysis. Commuters are aware of the hazard potential related to air pollution during commuting were 137 people (88.4%). Commuters with good perception of pollution were 104 people (67.1%). Commuters used masker during commuting was 125 people (80.6%). Healthy behavior (using masker) in commuting worker using KRL Commuter Line were affected by some factors both directly and indirectly. Knowledge and commuting experience toward healthy behavior using masker were two variables with a significant direct influence on healthy behavior using masker, and knowledge was also the only mediated variable with a significant indirect effect of education to healthy behavior (using masker).