bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification, Evolutionary And Expression Analyses of LEA Gene Family In Peanut (Arachis Hypogaea L.)
Authors: Huang RuoLan , Xiao Dong , Wang Xin , Shen Yi , Zhan Jie , Wang AiQing , He LongFei
Published: August 2021

Background: Late embryogenesis abundant (LEA) proteins are a group of highly hydrophilic glycine-rich proteins, which accumulate in the late stage of seed maturation and are associated with many abiotic stresses. However, few peanut LEA genes had been reported, and the research on the number, location, structure, molecular phylogeny and expression of AhLEAs was very limited. Results: In this study, 126 LEA genes were identified in the peanut genome through genome-wide analysis and were further divided into eight groups. Sequence analysis showed that most of the AhLEAs (85.7 %) had no or only one intron. LEA genes were randomly distributed on 20 chromosomes. Compared with tandem duplication, segmental duplication played a more critical role in AhLEAs amplication, and 93 segmental duplication AhLEAs and 5 pairs of tandem duplication genes were identified. Synteny analysis showed that some AhLEAs genes come from a common ancestor, and genome rearrangement and translocation occurred among these genomes. Almost all promoters of LEAs contain ABRE, MYB recognition sites, MYC recognition sites, and ERE cis-acting elements, suggesting that the LEA genes were involved in stress response. Gene expression analyses revealed that most of the LEAs were expressed in the late stages of peanut embryonic development. LEA3 (AH16G06810.1, AH06G03960.1), and Dehydrin (AH07G18700.1, AH17G19710.1) were highly expressed in roots, stems, leaves and flowers. Moreover, 100 AhLEAs were involved in response to drought, low-temperature, or Al stresses. Some LEAs that were regulated by different abiotic stresses were also regulated by hormones including ABA, brassinolide, ethylene and salicylic acid. Interestingly, AhLEAs that were up-regulated by ethylene and salicylic acid showed obvious subfamily preferences.Conclusions: AhLEAs are involved in abiotic stress response, and segmental duplication plays an important role in the evolution and amplification of AhLEAs. The genome-wide identification, classification, evolutionary and expression analyses of the AhLEA gene family provide a foundation for further exploring the LEA genes’ function in response to abiotic stress in peanuts.
Observation of light induced dynamical band structure via multi-band high harmonic spectroscopy
Authors: Uzan-Narovlansky Ayelet , Jimenez-Galan Alvaro , Orenstein Gal , Silva Rui , Arusi-Parpar Talya , Shames Sergei , Bruner Barry , Yan Binghai , Smirnova Olga , Ivanov Misha (Mikhail) , Dudovich Nirit
Published: August 2021

Intense light-matter interactions have revolutionized our ability to probe and manipulate quantum systems at sub-femtosecond time scales, opening routes to all-optical control of electronic currents in solids at petahertz rates, the time-scale of a single optical cycle. Such control typically requires electric field amplitudes ~V/A, when the voltage drop across a lattice site becomes comparable to the characteristic band gap energies. In this regime, intense light-matter interaction induces significant modifications of electronic and optical properties and is certain to dramatically modify the band structure of the light-dressed crystal. Yet, identifying and characterizing such modifications remains an outstanding problem. As the oscillating electric field changes from V/A to zero within a quarter-cycle of the driving field, does the band-structure follow, and how can it be defined? Here we address this fundamental question, proposing all-optical spectroscopy of strongly driven crystals, and probe laser-induced closing of the band-gap between adjacent conduction bands. Our work reveals the link between extreme nonlinear light matter interactions in strongly driven crystals to the sub-cycle modifications in their effective band structure.
First-Line Pembrolizumab Plus Chemotherapy for Extensive-Stage Small-Cell Lung Cancer: A United States-Based Cost-Effectiveness Analysis
Authors: Zhu Youwen , Hu Huabin , Ding Dong , Li Shuosha , Liao Mengting , Shi Yin , Huang Jin
Published: August 2021

Background: The clinical trial of Keynote-604 showed that pembrolizumab plus chemotherapy could generate clinical benefits for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). We aim to assess the efficacy and cost of pembrolizumab combined with chemotherapy in the first-line treatment setting of ES-SCLC from the United States (US) payers’ perspective.Methods: A synthetical Markov model was used to evaluate cost and effectiveness of pembrolizumab plus platinum-etoposide (EP) versus EP in first-line therapy for ES-SCLC from the data of Keynote-604. Lifetime costs life-years (LYs), quality adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. Furthermore, we performed subgroup analysis.Results: Pembrolizumab plus EP resulted in additional 0.18 QALYs (0.32 LYs) and corresponding incremental costs $113,625, resulting an ICER of $647,509 per QALY versus EP. the price of pembrolizumab had a significant impact on ICER. Probabilistic sensitivity analysis indicated that pembrolizumab combined chemotherapy may become a cost-effective option with a probability of 0%. Besides, subgroup analysis suggested that all subgroups were not cost-effective.Conclusion: From the perspective of the US payer, pembrolizumab plus EP is not a cost-effective option for first-line treatment patients with ES-SCLC at a WTP threshold of $150,000 per QALY.
HAO1-Mediated Oxalate Metabolism Promotes Lung Pre-Metastatic Niche Formation by Inducing Neutrophil Extracellular Traps
Authors: Zeng Zhicheng , Xu Shaowan , Wang Feifei , Peng Xin , Zhang Wanning , Zhan Yizhi , Ding Yanqing , Liu Ziguang , Liang Li
Published: August 2021

Background

Metabolic reprogramming has been shown to be involved in cancer-induced PMN formation, but the underlying mechanisms have been insufficiently explored.
Methods

HAO1 expression in lung tissues and alveolar epithelial cells were deteted by qPCR and Western blotting. The effect of HAO1 on the lung metastasis of cancer was investigated by orthotropic metastasis assay. Lungs and cells oxalate levels were determined using an oxalate assay kit. The effect of oxalate on neutrophil extracellular trap formation was investigated by immunofluorescence. The effect of oxalate on proliferation of breast cancer cells was revealed by immunofluorescence by colony formation assay.
Results

HAO1 was up-regulated in the alveolar epithelial cells of mice bearing metastatic breast cancer cells at the pre-metastatic stage. Upregulation of HAO1 led to oxalate accumulation in lung tissues and alveolar epithelial cells. Pharmacologic inhibition of HAO1 could effectively suppress the lung oxalate accumulation induced by primary cancer. Lung oxalate accumulation induced NET formation by activating NADPH oxidase. Lung oxalate accumulation promoted the proliferation of metastatic cancer cells by activating the MAPK signaling pathway. Breast cancer cells induced HAO1 expression and oxalate accumulation in alveolar epithelial cells by activating TLR3-IRF3 signaling.
Conclusion

These findings underscore the role of HAO1-mediated oxalate metabolism in cancer-induced lung PMN formation and metastasis. HAO1 could be an appealing therapeutic target for preventing lung metastasis of cancer.
An Intracellular Human Single Chain Antibody to Matrix Protein (M1) of H5N1 Virus
Authors: Sun He , Wu Guangmou , Zhang Jiyuan , Wang Yu , Qiu Yue , Man Hongyang , Zhang Guoli , Li Zehong , Yue Yuhuan , Tian Yuan
Published: August 2021

Background: Influenza virus matrix protein M1 is encoded by viral RNA fragment 7 and is the most abundant protein in virus particles. M1 is expressed in the late stages of viral replication and exerts functionality by inhibiting viral transcription. The M1 protein sequence is an attractive target for antibody drugs.Methods: The M1 protein sequence was amplified by RT-PCR using cDNA from the H5N1 virus as a template; the M1 protein was then expressed and purified. A human strain, high affinity, and single chain antibody (HuScFv) against M1 protein was obtained by phage antibody library screening using M1 as an antigen. A recombinant TAT-HuScFv protein was expressed by fusion with the TAT protein transduction domain (PTD) gene of HIV to prepare a human intracellular antibody against avian influenza virus. The differences between HuScFv and TAT-HUScFv were verified by various experiments and the amino acid binding site of the M1 protein was determined.Results: The M1 protein of H5N1, HuScFv, and TAT-HuScFv, were successfully purified and expressed by and in E. coli. Further analysis demonstrated that TAT-HuScFv inhibited the hemagglutination activity of the 300TCID50 H1N1 virus, thus providing preliminary validation of the universality of the antibody. After two rounds of M1 protein decomposition, the TAT-HuScFv antigen binding site was identified as Alanine (A) at position 239. Collectively, our data describe a recombinant antibody with high binding activity against the conserved sequences of avian influenza viruses. This intracellular recombinant antibody blocked the M1 protein that infected intracellular viruses, thus inhibiting the replication and reproduction of H5N1 viruses.Conclusion: Recombinant HuScFv was successfully identified using the Tomlinson (I+J) phage antibody library and successfully linked to the TAT protein transductive domain of the HIV virus. Compared with the HuScFv, the addition of the TAT peptide improved its ability to penetrate the cell membrane. A definite amino acid binding site was identified after the decomposition of M1 protein, thus providing a target and reference for the development of antibody drugs and the study of new drugs.
Can Passive Measurement of Physiological Distress Help Better Predict Suicidal Thinking?
Authors: Kleiman Evan , Bentley Kate , Maimone Joseph , Lee Sarah , Kilbury Erin , Fortgang Rebecca , Zuromski Kelly , Huffman Jeff , Nock Matthew
Published: August 2021

There has been growing interest in using wearable physiological monitors to passively detect the signals of distress (i.e., increases in autonomic arousal measured through increased electrodermal activity [EDA]) that may be imminently associated with suicidal thoughts. Before using these monitors in advanced applications such as creating suicide risk detection algorithms or just-in-time interventions, several preliminary questions must be answered. Specifically, we lack information about whether: (1) EDA concurrently and prospectively predicts suicidal thinking and (2) data on EDA adds to the ability to predict the presence and severity of suicidal thinking over and above self-reports of emotional distress. Participants (n=25, 56% female, M age= 33.48 years) completed six daily assessments of negative affect and suicidal thinking duration of their psychiatric inpatient stay and 28 days post-discharge, and wore on their wrist a physiological monitor (Empatica Embrace) that passively detects autonomic activity. We found that physiological data alone both concurrently and prospectively predicted periods of suicidal thinking, but models with physiological data alone had the poorest fit. Adding physiological data to self-report models improved fit when the outcome variable was severity of suicidal thinking, but worsened model fit when the outcome was presence of suicidal thinking. When predicting severity of suicidal thinking, physiological data improved model fit more for models with non-overlapping self-report data (i.e., low arousal negative affect) than for overlapping self-report data (i.e., high arousal negative affect).These findings suggest that physiological data, under certain contexts, may be useful in better predicting -- and ultimately, preventing -- acute increases in suicide risk. However, some cautious optimism is warranted since physiological data do not always improve our ability to predict suicidal thinking
Comparison of Domain Specific Connectivity Metrics for Estimation Brain Network Indices in Boys With ADHD-C
Authors: AYDIN SERAP , CETIN Fatih Hilmi , UYTUN Merve , BABADAG Zehra , GUVEN Ahmet Sami , ISIK Yasemen
Published: August 2021

The study includes Graph Theoretic advanced EEG analysis in order to investigate the impact of pharmacological treatment with osmotic release oral system-methylphenidate for a month in 18 boys (aged between 7-12 years) with Attention-Deficit-Hyperactivity Disorder, combined type. In analysis, neurofunctional dependency levels across the cortex are estimated by using six different connectivity estimation approaches based on three separate domains such as time (Pearson Correlation, Spearman Correlation), frequency (Directed Transfer Function, Partial Directed Coherence) and phase (Phase Locking Value, Phase Lag Index). All methods are examined for eyes-opened resting-state EEG segments of 2 sec over a single trial of 1 min in both pre- and post-treatment recordings. Then, five quantitative brain network indices of transitivity, clustering coefficients, assortativity, global efficiency and modularity are computed from connectivity estimations. Performance of connectivity estimators are compared to each other with respect to two-class classifications (pre-treatment features vs post-treatment features) by using Support Vector Machines driven by brain network indices. The highest classification accuracy of 80.74% is obtained with Pearson Correlation. Statistical one-way Anova test, pair-wise multiple comparison test and step-wise logistic regression modelling are all used to observe the most sensitive network index estimated from Pearson Correlations. In addition to quantitative results, statistical box-plots of the estimated network indices are shown graphically. When modularity index is excluded from the features, classification accuracy is increased to 83.79%. Overall results reveal that brain segregation and resilience are increased by the treatment. In particular, the most meaningful brain network measures can be estimated from time domain statistical correlations between resting-state eyes open EEG segments in order to understand the alterations in neuronal transmission mechanism across the cortex in response to a specific treatment in pediatric psychiatry.
Impact of green clay authigenesis on K–Mg–Fe sequestration in marine settings
Authors: Baldermann Andre , Banerjee Santanu , Czuppon György , Dietzel Martin , Farkas Juraj , Löhr Stefan , Moser Ulrike , Scheiblhofer Esther , Wright Nicky , Zack Thomas
Published: August 2021

Retrograde clay mineral reactions (i.e., reverse weathering), including glauconite formation, are first-order controls on element (re)cycling vs sequestration in modern and ancient marine sediments. Here, we report substantial K–Mg–Fe sequestration by glauconite formation in shallow marine settings from the Triassic to the Holocene, averaging 4 ± 3 mmol K·cm−²·kyr− 1, 4 ± 2 mmol Mg·cm−²·kyr− 1 and 10 ± 6 mmol Fe·cm−²·kyr− 1, which is ~ 2 orders of magnitude higher compared to deep-sea settings. Upscaling of glauconite abundances in shallow-water (< 200 m) environments predicts a global K–Mg–Fe uptake of ~ 0.05–0.06 Tmol K·yr− 1, ~ 0.04–0.06 Tmol Mg·yr− 1 and ~ 0.11–0.14 Tmol Fe·yr− 1. We conclude that authigenic clay elemental uptake had a large impact on the global marine K, Mg and Fe cycles throughout Earth`s history, in particular during ‘greenhouse’ periods with sea level highstand. Quantifying authigenic clay formation is key for better understanding past and present geochemical cycling in marine sediments.
Tracking Macrophages in Diabetic Neuropathy With Two-Color Nanoemulsions for Near-Infrared Fluorescent Imaging and Microscopy
Authors: Nichols James M. , Crelli Caitlin V. , Liu Lu , Pham Hoang Vu , Janjic Jelena M. , Shepherd Andrew J
Published: August 2021

Background The incidence of diabetes and diabetic peripheral neuropathy continues to rise, and studies have shown that macrophages play an important role in their pathogenesis. Here we present a novel two-color fluorescently labeled perfluorocarbon nanoemulsion to monitor phagocytic macrophages in vitro and in vivo using non-invasive near infrared fluorescence imaging and fluorescence microscopy in diabetic neuropathy. We next applied this nanoemulsion to the Leprdb/db model of Type 2 Diabetes Mellitus to track macrophages along the length of the peripheral sensory pathway of the hindlimb, where diabetic peripheral neuropathy tends to originate. Methods In vitro assessment of the nanoemulsion was performed by measuring fluorescent signal stability, colloidal stability, and macrophage uptake and subsequent viability. In vivo tracking of the nanoemulsion within Leprdb/db and wild-type mice was performed using both near infra-red fluorescent imaging and confocal microscopy to assess its biodistribution within phagocytic macrophages along the peripheral sensory apparatus of the hindlimb. Results In vitro experiments show two-color nanoemulsion had high levels of fluorescent and colloidal stability, and that it was readily incorporated into RAW 264.7 macrophages. In vivo tracking revealed distribution of the two-color nanoemulsion to macrophages within most tissues of Leprdb/db and wild-type mice which persisted for several weeks, however it did not cross the blood brain barrier. Reduced fluorescence was seen in sciatic nerves of both Leprdb/db and wildtype mice, implying that the nanoemulsion may also have difficulty crossing an intact blood nerve barrier. Additionally, distribution of the nanoemulsion in Lepr db/db mice was reduced in several tissues as compared to wild-type mice. This reduction in biodistribution appears to be caused by the increased number of adipose tissue macrophages in Leprdb/db mice. Conclusions The nanoemulsion in this study has the ability to identify phagocytic macrophages in the Leprdb/db model using both near infra-red fluorescent imaging and fluorescence microscopy. Based on the drug loading capacity of this new nanoemulsion and the role of inflammatory macrophages in diabetes, we foresee this agent being a useful tool in the assessment and treatment of diabetic peripheral neuropathy.
Brain and Breast Cancer Cells with PTEN Loss of Function Demonstrate Enhanced Durotaxis and RHOB Dependent Amoeboid Migration Using 3D Printed Scaffolds and Aligned Microfiber Tracts
Authors: Wieland Annalena , Strissel Pamela L. , Schorle Hannah , Bakirci Ezgi , Janzen Dieter , Beckmann Matthias W. , Eckstein Markus , Dalton Paul D. , Strick Reiner
Published: August 2021

Background: Glioblastoma multiforme (GBM) and triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with very poor patient outcomes. GBM uses axons and vessels as migratory cues to disseminate, however it is not known, if TNBC shares the same behavior. There is a need to understand brain tumor cell spreading and if GBM and TNBC have similar migration properties involving the signaling pathway RHOB-ROCK-PTEN. We tested for durotaxis, adherence and migration of GBM and TNBC using live-cell imaging and performed molecular analyses on three-dimensional (3D) structures.Methods: Aligned 3D printed scaffolds and microfibers were designed to mimic brain axon tracts and vessels for migration. GBM and TNBC cell lines, each with opposing PTEN genotypes, were analysed with RHO, ROCK and PTEN inhibitors and rescuing PTEN function using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while SEM, confocal microscopy and cell tracking addressed cell morphology. Results: GBM and TNBC with homozygote PTEN loss of function and RHOB high expression were amoeboid shaped and demonstrated enhanced durotaxis, adhesion and migration on 3D microfibers, in contrast to PTEN wildtype GBM and TNBC showing elongated cells and low RHOB. RNA-sequencing exhibited that RHOB was significantly the highest expressed gene in GBM PTEN loss of function cells. Pathway inhibitors and PTEN rescue of function verified an essential role of RHOB-ROCK-PTEN signaling for durotaxis, adhesion, migration, cell morphology and plasticity using 3D printed microfibers. Conclusions: This study validates a significant role of a PTEN genotype for cellular properties including durotaxis, adhesion and migration. GBM and TNBC cells with PTEN loss of function have a greater affinity for stiffer brain structures promoting metastasis. We propose the significance of PTEN and RHOB in cellular oncology not only for primary tumors, but also for metastasizing tumors, where RHOB inhibitors could play an essential role for improved therapy.
Metabolic Plasticity Improves Lobster´s Resilience to Ocean Warming but Not to Climate-driven Novel Species Interactions
Authors: Oellermann Michael , Fitzgibbon Quinn P. , Twiname Samantha , Pecl Gretta T.
Published: August 2021

Marine species not only suffer from direct effects of warming oceans but also indirectly via the emergence of novel species interactions. While metabolic adjustments can be crucial to improve resilience to warming, it is largely unknown if this improves performance relative to novel competitors. We aimed to identify if spiny lobsters – inhabiting a global warming and species re-distribution hotspot - align their metabolic performance to improve resilience to both warming and novel species interactions. We measured metabolic and escape capacity of two Australian spiny lobsters, resident Jasus edwardsii and the range-shifting Sagmariasus verreauxi, acclimated to current average- (14.0°C), current summer- (17.5°C) and projected future summer- (21.5°C) habitat temperatures. We found that both species decreased their standard metabolic rate with increased acclimation temperature, while sustaining their scope for aerobic metabolism. However, the resident lobster showed reduced anaerobic escape performance at warmer temperatures and failed to match the metabolic capacity of the range-shifting lobster. We conclude that although resident spiny lobsters optimise metabolism in response to seasonal and future temperature changes, they may be unable to physiologically outperform their range-shifting competitors. This highlights the critical importance of exploring direct as well as indirect effects of temperature changes to understand climate change impacts.
The Protective Effects of GPR55 Against Hippocampal Neuroinflammation and Neurogenic Damage in CSDS Mice
Authors: Shen Shiyu , Yu Rui , Li Wei , Liang Ling-Feng , Han Qiuqin , Huang Huijie , Li Bing , Xu Shifen , Wu Gencheng , Zhang Yu-Qiu , Yu Jin
Published: August 2021

BackgroundDepression is one of the most prevalent mental illnesses in the world today, the onset of depression is usually accompanied by neuroinflammation and neurogenic damage. Recently, G protein coupled receptor 55 (GPR55) has been associated with mood regulation as a third kind of cannabinoid receptor, and the activation of GPR55 was demonstrated recently to have a neuroprotective effect on hippocampal neurogenesis against inflammatory insult. However, its role in regulating depression and anxiety remains poorly understood.Methods10-day chronic social defeat stress (CSDS) was utilized as an animal model of depression to explore the potential antidepressant effect of GPR55 agonist and electroacupuncture (EA), a common therapy for depression in China. Several behavioral tests i.e. forced swimming test, open field test and elevated plus maze were performed to evaluate the depression- and anxiety-like behaviors in mice. Expression of GPR55, hippocampal neuroinflammation, and neurogenesis were detected using immunohistochemistry, western blot and RT-PCR. Then, the effect of a GPR55 agonist, O-1602 on depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis was examined. Furthermore, the potential antidepressant effect of 3-week EA treatment was also evaluated in another independent experiment. In the experiment, the behaviors and hippocampal neuroinflammation and neurogenesis were also subsequently examined.ResultsAfter CSDS, the protein level of GPR55 was decreased only in susceptible mice but the mRNA expression was not significantly different in all CSDS mice. Additionally, depression- and anxiety-like behaviors are accompanied by neuroinflammation and reduced neurogenesis in the hippocampus. And the activation of GPR55 during the process of CSDS prevented the development of depression- and anxiety- like behaviors, as well as hippocampal neuroinflammation and neurogenetic damage. Similarly, EA alleviated the depression- and anxiety-like behaviors, hippocampal neuroinflammation, and neurogenetic damage as well as decreased protein level of GPR55 in hippocampus induced by CSDS.ConclusionsOur research demonstrated that activation of hippocampal GPR55 could rescue depression and anxiety phenotypes, reduce hippocampal neuroinflammation, and enhance hippocampal neurogenesis. Moreover, GPR55 might be involved in the beneficial effect of EA on depression.
Feasibility and Safety of Early Mobilization in Critically Ill Children: A Prospective Observational Study
Authors: Moerman Damien , Reychler Grégory , Bednarek Pauline , de Cléty Stéphan Clément , Detaille Thierry , Houtekie Laurent
Published: August 2021

The study aims to evaluate the feasibility and the safety of early mobilization in critically ill children under 2 years and its impact on comfort scores. This prospective, monocenter clinical trial was conducted in a tertiary care pediatric intensive care unit in Belgium. Twenty children were recruited to the study. Early mobilization was done between 24 and 48 hours of admission. Mobilization of upper and lower limbs was performed according to practice protocol. The heart rate (HR), respiratory rate (RR), systolic and diastolic blood pressures (SBP and DBP, respectively) and pulsed oxygen saturation were recorded before mobilization, immediately after the treatment and after 10, 30 and 60 minutes. The EDIN score for the extubated children and the COMFORT-B score for the intubated children were used in order to evaluate comfort. The primary outcome was the feasibility and safety of early mobilization. The secondary outcome was to evaluate the impact of early mobilization on comfort. Sixteen sessions were completed and 4 sessions of mobilization were interrupted because of important agitation. HR, SBP and DPB showed no change immediately after the mobilization, compared with baseline. RR and SpO2 were similar at the different times. Agitation had impact on the EDIN and COMFORT-B scores in children whose session was interrupted. No adverse events were reported.Conclusions: Early mobilization is feasible and safe in the majority of critically ill children under 2 years even if the agitation is described as an adverse event. Early mobilization does not influence the cardio-respiratory parameters.Clinical Trial Registration number and date of registration: Clinicaltrials.gov, NCT02958124, 10/09/2017
Ionospheric Irregularities During Disturbed Geomagnetic Conditions Over Argentinian EIA Region
Authors: González Gilda de Lourdes
Published: August 2021

Ionospheric irregularities can severely degrade radio communication and navigation systems. Geomagnetic storms may affect the generation of these irregularities in a way that is not yet fully understood. To improve the forecasting of this phenomenon, we need to study the ionosphere in different regions of the world, and in particular in the equatorial ionization anomaly (EIA) where irregularities are usually more intense. This study analyses the effect of geomagnetic storms on ionospheric irregularities. We examined the occurrence of irregularities at the southern crest of the EIA in Argentina (Tucumán, 26.9°S, 294.6°E, dip latitude 15.5° S) during three intense and one moderate geomagnetic storm of different solar sources, between 2015 and 2018. We used data from an ionosonde, a Global Positioning System (GPS) receiver and magnetometers. Ionogram spread-F, the F-layer bottom side (h'F), the critical frequency of the F2-layer (foF2), the rate of TEC index (ROTI) and the S4 scintillation index were analysed. The data show irregularities were present as range spread-F and moderate TEC fluctuations in one storm: 27 May 2017 (a coronal mass ejection CME-driven storm occurred on local winter), and were absent in the other events. We suggest that eastward disturbance dynamo electric field and over-shielding prompt penetration electric fields may create favourable conditions for developing these irregularities. Whereas, westward storm time electric fields might inhibit the growth of irregularities during the other storms considered. During co-rotating interaction region CIR-driven storms, the westward disturbance dynamo electric field may be associated with the non-occurrence of irregularities.
Static Mechanical, Heat Deflection And Ageing Properties of Cocos Nucifera Filler Reinforced Vinyl Ester Polymer Composites
Authors: Gnanaraj J. David , Mothilal S. , Vignesh V. , Karthick T. , Ismail Sikiru O. , nagarajan rajini , Rabi B. Raja Mohamed , Siengchin Suchart , Mohammad Faruq
Published: August 2021

Recently, natural filler reinforced polymer composites are important materials for various engineering applications. Hence, this present work focuses on utilization of coconut shell powder (CSP) as a filler in vinyl ester (VE) resin to produce particulate composite specimens. The particulate composite plates with various weights or filler contents from 5 to 30 wt% were fabricated, using compression molding technique. The fabricated composites were subjected to tensile, flexural, impact, hardness, heat deflection and swelling behavior tests to obtain their corresponding material properties. Energy dispersive X-ray (EDX) analysis was carried out on the coconut shell powder/vinyl ester (CSP/VE) composite specimens to investigate into the presence of their elements, in addition to the aforementioned tests. From the experimental results obtained, it was observed that the optimum mechanical properties of CSP/VE composites were obtained at 15 wt% of filler content, having tensile, flexural and impact strengths of 38.70, 105.13 MPa and 33.04 kJ/m2, respectively. Also, the heat deflection temperature (HDT) results varied from 158 (0 wt%, neat VE resin) to 171 oC along various percentages of filler contents. Lastly, the morphological study/analysis of the fractured CSP/VE composite specimens was conducted by using a scanning electron microscope (SEM) to confirm the experimental data/results obtained. It was evident that CSP/VE composite structures could be potential substitutes for some synthetic composites. Also, they are suitable for various engineering applications in aerospace, electrical/electronics and automobile industries, based on their properties.
CircRUNX1 Drives Immune Evasion and anti-PD1 Immunotherapy Resistance in Lung Adenocarcinoma by the miR-4739/PCSK9/MHC I Axis
Authors: Zhang Peng-Fei , Xu Yi-Fan , Zhang Ling-Xian , Wu Jing , Fan Yue
Published: August 2021

Background: Lung adenocarcinoma (LUAD) is the commonest pathological subtype of lung-derived malignant tumor. Blocking the immune checkpoints interaction between programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) via naturalizing PD-1 or PD-L1 monoclonal antibody is proved to be a effective therapeutic method for drive gene negative LUAD. Dysregulation of circular RNA (circRNA) is a hallmark of cancer and has a critical role in the progression of cancers, including LUAD. However, the exact role of circular RUNX family transcription factor 1 (circRUNX1, hsa_circ_0002360) in LUAD remains unknown. Methods: The expression levels of circRUNX1, miR-4739, and proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA were examined by quantitative real-time polymerase chain reaction (qRT-PCR). PCSK9, histocompatibility complex I (MHC I), CD8, and Foxp3 protein expression was examined by immunohistochemistry (IHC) or western blot analysis. In vivo assay was carried out to determine the biological function of circRUNX1 on LUAD immune evasion in vivo. The binding relationship between miR-4739 and circRUNX1 or PCSK9 was predicted and verified by Starbase V3.0 online databases, dual-luciferase reporter assay, and RNA-pull down assay. Results: CircRUNX1 expression was frequently increased in LUAD tissues, and forced circRUNX1 expression was associated with poor prognosis, big tumor size, advanced stage, and resistance to anti-PD1 immunotherapy in LUAD patients. Functionally, circRUNX1 overexpression promoted LUAD immune evasion in vivo. In addition, our results demonstrated that circRUNX1 could sponge miR-4739, subsequently, upregulating the PCSK9 expression and promoting to LUAD immune evasion. Conclusion: circRUNX1 promoted cancer immune evasion and resistance to anti-PD1 immunotherapy by regulate miR-4739/PCSK9/MHC I axis in LUAD. Taken together, our findings indicate that circRUNX1 may be a promising therapeutic target for improve the anti-PD1 therapy effect in LUAD patients.
Association of Childhood Metabolic Syndrome and Metabolic Phenotypes with the Carotid Intima-Media Thickness (CIMT) in Early Adulthood: Tehran Lipid and Glucose Study
Authors: Valizadeh Majid , Tasdighi Erfan , Barzin Maryam , Hariri Ramyar , Mahdavi Maryam , Dehghan Pooneh , Moghaddam Amin Momeni , Azizi Fereidoun , Hosseinpanah Farhad
Published: August 2021

Background: The prevalence of metabolic syndrome (MetS) during adolescence has shown an increasing trend. This study aimed to investigate the association of MetS and metabolic phenotypes with a high carotid intima-media thickness (CIMT) in early adulthood in the framework of a large cohort study. Methods: MetS was defined as proposed by Cook, de Ferranti, the National Cholesterol Education Program (NCEP), and the pediatric International Diabetes Federation (IDF). Metabolic phenotypes were defined based on the binary clustering of cardiovascular risk factors. The participants were followed up for 18.2 years. Multivariate-adjusted odds ratios (ORs) were calculated for a high CIMT incidence (≥95th percentile).Results: In this study, 862 adolescents (52.3% males), with the mean age of 13.4±2.2 years, were included. The presence of MetS, based on the definitions proposed by Cook (OR=1.90, 95% CI: 1.01-3.57, P=0.046) and de Ferranti (OR=1.74; 95% CI: 1.04-2.90, P=0.033), was associated with the increased risk of a high CIMT in early adulthood. Metabolic phenotypes, including high waist circumference (WC)/hypertension (HTN), high WC/low high-density lipoprotein-cholesterol (HDL-C), and high triglyceride (TG)/high WC, showed higher risks of a high CIMT. However, these positive associations become insignificant after adjusting for the adulthood BMI, except for the high WC/low HDL-C phenotype (OR=2.04, 95% CI: 1.02-4.11, P=0.044). Conclusion: The high WC/low HDL-C phenotype had a better predictive value and could be used as a simpler alternative for MetS to identify adolescents with a higher risk of high CIMT during early adulthood.
On the Milling Strategy in Machining Curved Surfaces Based on Minimum Stress Concentration by a 3-axis Machining Center
Authors: Li Hang , Zhang Peirong , Su Guosheng , Du Jin , Xu Chonghai
Published: August 2021

3-axis computer numerical control machining centers are used in machining due to their simple operation. When machining curved surfaces, the 3-axis CNC machining centers use interpolation lines segment to fit the curved surfaces. The quality of the machined surface is affected by the length of the interpolation line segment. Sharp corners are formed at the junction of straight segments. The appearance of sharp corners will lead to increased stress concentration. To study the relationship between surface quality and interpolation straight line in surface processing, this paper establishes the mathematical model of surface topography in 3-axis ball-end milling curved surfaces based on the acceleration and deceleration control. Based on the surface topography model, the surfaces stress concentration factor analysis is carried out in machining curved surfaces with variable curvatures with different lengths of interpolation lines. The results show that when the length of interpolation lines and the radius of curvature are kept constant, the stress concentration factor decreases with the increase of the central angle. When the length of the interpolation lines and the central angle are kept constant, the stress concentration factor decreases with the increase of the radius of curvature. When the radius of curvature and the central angle are kept constant, the stress concentration factor increases as the length of the interpolation lines increases. A method of selecting the length of interpolation lines based on the surface’s stress concentration is proposed. Through the optimization of the tool path, the quality of the machined surfaces can be improved.
Is the Cardiac Magnetic Resonance Cine Images Capable of Differentiating Between LVEF-preserved Light-chain Amyloidosis and Hypertrophic Cardiomyopathy? －the Value of Left Atrial Parameters
Authors: Lu Jianyao , Zhou Wen , Qiao Jinhan , Zhao Peijun , Huang Lu , Tang Dazhong , Xia Liming
Published: August 2021

Purpose: Due to the limited application of late gadolinium enhancement (LGE) in patients with renal insufficiency and the lack of advanced mapping technique, non-invasively discriminating left ventricular ejection fraction (LVEF)-preserved light-chain amyloidosis (AL) from hypertrophic cardiomyopathy (HCM) with similar left ventricular (LV) hypertrophy was challenging. The aims of this study were to evaluate left atrial (LA) morphology and function in LVEF-preserved AL patients using CMR cine images and to investigate the ability of CMR-derived LA parameters in discriminating LVEF-preserved AL from HCM.Methods and results: Thirty-eight confirmed LVEF-preserved AL patients and 38 HCM patients as well as 20 healthy controls were enrolled in this retrospective study. Morphological and functional parameters of LA and LV were measured in multi-plane cine images. Receiver operator characteristics curves were generated to estimate the discriminative ability of parameters. The LA active contractile function of AL and HCM patients were both significantly impaired compared to the control, and the impairment of AL patients was severer than that of HCM (all P < 0.05). In morphological aspect, thickened maximum atrial septal thickness (ASHmax) was found in AL group with regard to HCM and control. Combining ASHmax and LA functional parameters had excellent discriminative ability between AL and HCM (area under the curve [AUC] > 0.9).Conclusions: The combination of ASHmax and LA function was able to perform accurately non-invasive differentiating diagnosis between AL and HCM patients in limited clinical condition, and it could helpfully complemented and extended the current AL diagnostic strategies.
Can Thymidine Kinase 1 Detect Small Invisible Malignant Tumours?
Authors: Zhou Ji , Li Huijun , Fang Cong , Tan Junye , Gao Peng , Jin Cuicui , Liu Sonbo , Li Jin , Wang Yu , He Ellen , Skog Sven
Published: August 2021

Objectives. Early detection of malignant tumour is a prerequisite for a successful treatment. Here we investigate if thymidine kinase 1 is more sensitive than imaging technology to discover small invisible malignant tumours.Material and Methods. The cellular concentration of TK1 was determined by an automatic chemiluminescence analyzer of magnetic particle immune sandwich minimum. The primary and secondary antibodies linked to the magnetic beads were chicken anti-human thymidine kinase 1 IgY-polyclonal antibodies (IgY). The minimum number of cells able to detect by the automatic chemiluminescence analyzer were determined based on the cellar TK1 concentration of low and high TK1 cell lines of known cell count.Results. The TK1 concentration of malignant cell was found to be 0.021 pg/cell. Assuming 200 pg of total protein/cell, TK1 corresponds to 0.01 % of the total protein/cell. The concentration of TK1 in human blood serum of malignant patients is in the range of 2-10 pmol/l (pM), corresponding to about 50 x106 growing cells that release TK1 into 5 litre blood. The limit visibility by imaging of a tumour is about 1 mm in diameter, corresponding to about 109cells of a cell diameter of 1µm. Conclusion. TK1 is more sensitive than imaging.
A Novel Betaretrovirus Discovered in Cattle With Neurological Disease and Encephalitis
Authors: Hierweger Melanie M. , Koch Michel C. , Kauer Ronja V. , Bagó Zoltán , Oevermann Anna , Bertoni Giuseppe , Seuberlich Torsten
Published: August 2021

Background: The majority of emerging infectious diseases in humans are of animal origin, and many of them are caused by neuropathogenic viruses. Many cases of neurological disease and encephalitis in livestock remain etiologically unresolved, posing a constant threat to animal and human health. Thus, continuous extension of our knowledge of the repertoire of viruses prone to infect the central nervous system (CNS) is vital for pathogen monitoring and the early detection of emerging viruses. Using high-throughput sequencing (HTS) and bioinformatics, we discovered a new retrovirus, bovine retrovirus CH15 (BoRV CH15), in the CNS of a cow with non-suppurative encephalitis. Phylogenetic analysis revealed the affiliation of BoRV CH15 to the genus Betaretrovirus.Results: BoRV CH15 genomes were identified prospectively and retrospectively by PCR, RT-PCR, and HTS, with targeting of viral RNA and proviral DNA, in six additional diseased cows investigated over a period of >20 years and of different geographical origins. The virus was not found in brain samples from healthy slaughtered control animals (n=134). We determined the full-length proviral genomes from six of the seven investigated animals and, using in situ hybridization, identified viral RNA in the cytoplasm of cells morphologically compatible with neurons in diseased brains.Conclusions: Further screening of brain samples, virus isolation, and infection studies are needed to estimate the significance of these findings and the causative association of BoRV CH15 with neurological disease and encephalitis in cattle. However, with the full-length proviral sequences of BoRV CH15 genomes, we provide the basis for a molecular clone and further in vitro investigation.
Effect of Inflammatory Stress on Neural Stem Cells Behaviour: A Rescue Effect of Phosphatidylcholine by Modulating Neuronal Plasticity.
Authors: Magaquian Dario , Ocaña Susana Delgado , Perez Consuelo , Banchio Claudia
Published: August 2021

The balances between NSCs growth and differentiation, and between glial and neuronal differentiation play a key role for brain regeneration after any pathological conditions. It is well known that the nervous tissue shows a poor recovery after injury due to the factors present in the wounded microenvironment, particularly inflammatory factors, that prevent neuronal differentiation. Thus, it is essential to generate a favourable condition for NSCs and conduct them to differentiate towards functional neurons. Here, we show that neuroinflammation has no effect on NSCs proliferation but induces an aberrant neuronal differentiation that gives rise to dystrophic, non-functional neurons. This is perhaps the initial step of brain failure associate to many neurological disorders. Interestingly, we demonstrate that phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation even under inflammatory stress by modifying the commitment of post-mitotic cells. The pro-neurogenic effect of PtdCho increases the population of healthy normal neurons. In addition, we provide evidences that this phospholipid ameliorates the damage of neurons and, in consequence, modulates neuronal plasticity. These results contribute to our understanding of NSCs behaviour under inflammatory conditions, opening up new venues to improve neurogenic capacity in the brain.
The Safety and Effectiveness of Automatic Pedicle Screw Trajectory Planning Based on CT Values: An in Vitro Osteoporosis Model Study.
Authors: Liu JiaBin , Zuo Rui , Zheng Wenjie , Li ChangQing , Zhang Chao , Zhou Yue
Published: August 2021

BackgroundPedicle screw placement in patients with osteoporosis is a serious clinical challenge. The bone mineral density (BMD) of the screw trajectory has been positively correlated with the screw pull-out force, while the CT value has been linearly correlated with the BMD. The purpose of this study was to establish an in vitro osteoporosis model and verify the safety and effectiveness of automated pedicle screw planning software based on CT values in this model.MethodsTen vertebrae (L1-L5) of normal adult pigs were randomly divided into a decalcification group and a control group. In the decalcification group, the vertebral bodies were decalcified with Ethylenediaminetetraacetic acid (EDTA) to construct an in vitro osteoporosis model. In the decalcification group, automatic planning (AP) and manual planning (MP) were used to plan the pedicle screw trajectory on the left and right sides of the pedicle, respectively, and MP was used on both sides of the control group. CT values of trajectories obtained by the two methods were measured and compared. Then, 3D-printed guide plates were designed to assist pedicle screw placement. A biomechanical instrument was used to measure the pull-out force of the trajectory obtained by the two methods.ResultsAfter decalcification, the T' value of the vertebral body decreased from -0.03 ± 1.03 to -3.03 ± 0.29 (P <0.05). In the decalcification group, the MP trajectory CT value was 2167.28 ± 65.62 Hu, the AP trajectory CT value was 2723.96 ± 165.83 Hu, and the MP trajectory CT value in the control group was 2242.94 ± 25.80 Hu (P<0.05). In the decalcified vertebrae, the screw pull-out force of the MP group was 48.6% lower than that of the control group (P <0.05). The pull-out force of the AP trajectory was 44.7% higher than that of the MP trajectory (P <0.05) and reached 97.4% of the MP trajectory in the control group (P >0.05).ConclusionAutomatic planning of the pedicle screw trajectory based on the CT value can obtain a higher screw pull-out force, which is a valuable new method of pedicle screw placement in osteoporotic vertebral bodies.
Influencing Factors of HLA-DR Expression in Orbital Preadipocytes of Patients With Thyroid Associated Ophthalmopathy
Authors: Lei Xiang , Liu Hanhan , Ren Hong , Xu Xueliang , Deng Zhihong
Published: August 2021

Purpose: To investigate the effects of IFN-γ, IL-6, PPAR-γ agonist pioglitazone and PPAR-γ antagonist GW9662 on preadipocyte proliferation and HLA-DR expression.Methods: Preadipocytes were cultured from thyroid associated ophthalmopathy patients and health ocular trauma patients and induced to differentiate in vitro. IFN-γ, IL-6, PPAR-γ agonist pioglitazone and PPAR-γ antagonist GW9662 were added to preadipocytes to observe their effects on proliferation and HLA-DR expression.Results: IFN-γ significantly increased the levels of HLA-DR mRNA and protein in preadipocytes which are cultured from thyroid associated ophthalmopathy patients. IFN-γ also reduced the accumulation of lipid in the cytoplasm of preadipocytes. On the contrary, IL-6 had no effect on the expression of HLA-DR. Pioglitazone increased the expression of HLA-DR in orbital preadipocytes of TAO patients, and promoted the proliferation and intracellular lipid accumulation of preadipocytes. On the contrary, GW9662 decreased the expression of HLA-DR in orbital preadipocytes of TAO patients, and reduced the proliferation and intracellular lipid accumulation of preadipocytes.Conclusion: IFN-γ increase the expression of HLA-DR in TAO orbital preadipocytes after differentiation. PPAR - γ antagonists may be beneficial to the treatment of TAO.