bluuebunny/crossref_metadata_2025 huggingface dataset:
On Gaussian Curvature and Membrane Fission
Authors: Rueda-Contreras Mara Denisse , Gallen Andreu F. , Romero-Arias J. Roberto , Hernandez-Machado Aurora , Barrio Rafael A.
Published: February 2021

We propose a three-dimensional mathematical model to describe dynamical processes of membrane fission. The model is based on a phase field equation that includes the Gaussian curvature contribution to the bending energy. With the addition of the Gaussian curvature energy term numerical simulations agree with the predictions that tubular shapes can break down into multiple vesicles. A dispersion relation obtained with linear analysis predicts the wavelength of the instability and the number of formed vesicles. Finally, a membrane shape diagram is obtained for the different Gaussian and bending modulus, showing different shape regimes.
In Silico Analysis of 716 Natural Bioactive Molecules Form Atlantic Ocean Reveals Candidate Molecule to Inhibit Spike Protein 
Authors: Habib Peter T. , Saber-Ayad Maha , Hassanein Sameh E.
Published: February 2021

COVID-19, a new pandemic of coronavirus (CoV), was reported in Wuhan, China, in 2019. No specific drugs are available and investigations regarding COVID-19 treatment are proceeding. Lan et al. (2020) successfully crystallized the COVID-19 spike receptor-binding domain bounding to the ACE2 receptor, which is a potential drug target. The present study aimed to assess 716 bioactive compounds found in the South Atlantic Ocean as potential COVID-19 Spike inhibitors, using a molecular docking study. Molecular docking was performed using Autodock Vina to analyze the probability of docking. COVID-19 Spike was docked with several compounds, and docking was virtually screened by Chimera, Pymol, and Biovia Discovery Studio and test for draggability using SWISSADME. The analysis shows that 11 NPs out of 716 are predicted to be Spike inhibitors by blocking the amino acids responsible for binding Spike to ACE2. However, further findings are necessary to experimentally investigated for their potential medicinal use.
WITHDRAWN: Zinc Substituted Nickel-cobalt Nano-ferrites via Citrate-gel Auto-combustion Method for High-frequency Applications: Studies on Crystal Structure and Dielectric Properties
Authors: Oumezzine Marwene , Iuga Alin Iuga , ENCULESCU Monica , Galca Aurelian Catalin
Published: February 2021

Ni0.8−xZnxCo0.2Fe2O4 (x = 0.0, 0.05, 0.10 and 0.20) were prepared by citrate-gel auto-combustion method. The structural investigation using powder X-ray diffraction (XRD) showed the formation of single-phase cubic spinel structures with Fd-3m space group for all prepared samples. As the Zn2+ concentration is increased, the values of the lattice constant, tetrahedral and octahedral bond lengths undergo significant change. The absolute experimental lattice parameters are closely to the Vegard’ s law derived ones, suggesting that the cations concentration fairly correspond with those calculated prior chemical synthesis. Fourier transform infrared (FTIR) absorption bands at 594–400 cm− 1 confirm the formation of spinel structure. The values of dielectric constant and loss tangent were reported to decline with frequency and the Zn2+composition (x). Incorporation of Zn at nickel-cobalt resulted in decrease in ac conductivity at RT. Here, we report a low loss tangent factor of the order of 8 × 103for the sample with x = 0.20 make this composition suitable for high frequency applications. Imaginary electric modulus studies unveil the presence of non-Debye type of dielectric relaxation phenomenon. The activation energy of our samples calculated from modulus spectra is found to increase with further substitution of Zn2+ concentration.
Pyroelectric Catalysis-based “Nano-lymphatic” Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy
Authors: He Yuchu , Li Zhuo , Cong Cong , Ye Fei , Yang Jingyue , Zhang Xuwu , Yuan Yi , Ma Zhenhe , Zhang Kaiqing , Lin Yang , Zheng Lizhao , Gao Dawei
Published: February 2021

Owing to deficiency of lymphatic reflux in the tumor, the retention of tumor interstitial fluid causes the aggravation of tumor interstitial pressure (TIP), which leads to unsatisfactory tumor penetration of nanomedicine. It is the main inducement of tumor recurrence and metastasis. Herein, we design a pyroelectric catalysis-based “Nano-lymphatic” to decrease the TIP for enhanced tumor penetration and treatments. It realizes photothermal therapy and decomposition of tumor interstitial fluid under NIR-II laser irradiation after reaching the tumor, which reduces the TIP for enhanced tumor penetration. Simultaneously, reactive oxygen species generated during the pyroelectric catalysis can further damage deep tumor stem cells. The results indicate that the “Nano-lymphatic” relieves 52% of TIP, leading to enhanced tumor penetration, which effectively inhibits the tumor proliferation (93.75%) and recurrence. Our finding presents a novel strategy to reduce TIP by pyroelectric catalysis for enhanced tumor penetration and improved treatments, which is of great significance for drug delivery.
Evolutionary Game of Environmental Investment under National Environmental Regulation in China
Authors: Sun Tao , Feng Qiang
Published: February 2021

With the rapid development of social economy, the deterioration of environment has become more and more serious, it is urgent to find a balance between economic development and environmental protection. Therefore, enterprises are appealed to invest in environmental protection and local municipalities are appealed to supervise the environmental behaviors of enterprises, while central government plays a role of regulation. In order to study the preconditions for a better environmental strategy combination of local municipalities and enterprises, an evolutionary game theory was first constructed in this paper, then the evolutionary stable strategy (ESS) of local municipalities and enterprises under different scenarios was examined, and finally a simulation was used to test the results of the analysis. The results indicate that central government’s regulation has influence on the strategies chosen by local municipalities and enterprises, the larger the degree of central government’s incentives are, the more possible local municipalities and enterprises would choose environment-friendly strategies; and the intensity of central government's regulation, the cost and benefits of local municipalities’ supervision, and the cost and benefits of enterprises' environmental investment are the key influence factors.
Differentiation and Maturation Effect of All-trans Retinoic Acid on Cultured Fetal RPE and Stem Cell-Derived RPE Cells for Cell-Based Therapy
Authors: Yan Tingyu , Yang Na , Hu Wei , Zhang Xinxin , Li Xuedong , Wang Youjin , Kong Jun
Published: February 2021

Background: Phase I/II clinical trials using fetal retinal pigment epithelium (fRPE), human embryonic stem cell (hESC)-derived RPE, or human induced pluripotent stem cell (hiPSC)-derived RPE as potential sources of materials for cell-based therapy to treat degenerative retinal diseases have been carried out during the past decade. Challenges for successful translational cell-based therapy include cell manufacture, cell quality, cell storage, and cell behavior in vivo. In this study, we investigated the culture-induced changes in passaged fetal RPE, hESC-RPE and hiPSC-RPE cells in vitro and explored the differentiation and maturation effect of all-trans retinoic acid (ATRA) on those RPE cells. Methods: A total of 9 fetal RPE cell lines, hESC-RPE and hiPSC-RPE cell lines were set up using previously described methods. The culture-induced changes in subsequent passages caused by manipulating plating density, dissociation method and repeated passaging were studied by microscope, real-time quantitative PCR, western blot and immunofluorescent assays. Gene and protein expression and functional characteristics of fRPE, hESC-RPE and hiPSC-RPE incubated with ATRA at different concentration were also evaluated.Results: Compared with fRPE, hESC-RPE and hiPSC-RPE showed decreased gene and protein expression of RPE markers. Passage 3 RPE of all three types seeded at a density of 6×105 and 9x105 cells/mL in basal medium maintained pigmented polygonal, cobblestone-like morphology. RPE cells underwent mesenchymal changes showing increased expression of mesenchymal markers including a-SMA, N-cadherin, fibronectin and decreased expression of RPE markers including RPE65, E-cadherin and ZO-1, as a subsequence of low plating density, inappropriate dissociated method, and repeated passaging. fRPE, hESC-RPE and iPSC-RPE treated by ATRA at different concentrations showed increased expression of RPE markers such as RPE65, bestrophin (BEST) and CRALBP, and increased expression of negative complement regulatory proteins (CRP) including complement factor H (CFH), CD46, CD55 and CD59, and increased transepithelial resistance (TER) as well.Conclusion: Although hESC and hiPSC-derived RPE are morphologically similar to fRPE, and also have the tendency to undergo epithelial-to-mesenchymal transition (EMT) changes during the culturing and passaging process in vitro, differences in protein and gene expression among three RPE types exist. Moreover, ATRA can increase RPE markers expression, as well as to increase the expression levels of CRPs gene and protein in fRPE and stem cell-derived RPE.
Effects of Hydro-Meteorological Factors on Streamflow Withdrawal for Irrigation
Authors: Sung Jang Hyun , Baek Donghae , Ryu Young , Seo Seung Beom
Published: February 2021

The relationships between a variety of hydro-meteorological variables and irrigation water use rates (WUR) were investigated in this study. Standardized Precipitation Index (SPI), Potential Evapotranspiration (PET), and Normalized difference vegetation index (NDVI) are explored in order to identify the relationship with the WUR. The Yeongsan river basin which agricultural land is mostly occupied by well-irrigated paddy was used for the pilot study. 4 different temporal scale of SPI-3, 6, 9, and 12-were tested, and PET was calculated using Thornthwaite method. To calculate NDVI, the surface spectral reflectance data, which was acquired by Moderate Resolution Imaging Spectroradiometer (MODIS) equipped on Terra satellite, were used. As a result, there was a statistically significant relationship between SPI9 and the WUR during drought period in which negative values of SPI9 occurred. Besides, the WUR was strongly correlated with both PET and NDVI. Comparing to SPI, the variability of WUR in this study area was more sensitively affected by PET and NDVI which can cause potential lack of agricultural water supply. Based on the finding of this study, it implies that SPI9, PET, and NDVI are the critical factors for predicting water withdrawal during drought conditions so that they can be used for the irrigational water use management. Although the findings of this study have been suggested by a few previous studies, this study has its novelty in quantifying those discussions using actual field observations of streamflow withdrawal for irrigation.
Nominalizations: Application of Grammatical Metaphor in the News Articles of Bangladesh-China Relations
Authors: Akanda Muhammad Anisur Rahman
Published: February 2021

This study, within the framework of Halliday’s Systemic Functional Grammar, aims to find out the types of nominalization and their functions in the news articles of Bangladesh-China relations. Bangladesh established the diplomatic relation with China on 4 October 1975. Since then the BSS has shown great interest in the relationship between the two countries. By combining the qualitative and quantitative methods, this paper includes 140 news articles from the BSS on the topic (1975-2016). Grammatical Metaphor Theory is applied to identify the specific functions of nominalization in the news articles, which are calculated by the Wordsmith Tools. The findings show that process nominalization is the top-highest frequently metaphor (40.3%), while circumstance nominalization is the second-highest metaphor (35.8%). Further, relator nominalization is the third-highest metaphor (14.2%), while quality nominalization is the fourth-highest metaphor (8.4%). The lowest nominalization is entity nominalization, which is only 1.4%. The findings also show that process nominalization can increase the level of objectivity and conciseness of Bangladesh-China relations. By contrast, quality nominalization can increase the distance between the readers and the editors. Relator and entity nominalizations are rarely used in the news articles of the BSS. Further, practical implications are drawn for the readers about the function of nominalization in the news articles, which are concise, objective, and formal. Therefore, this paper will be helpful for those, who are interested in the study of the relations between Bangladesh and China.
Historic Grazing Enhances Root-Foraging Plasticity and Assimilation But Not Absorbability For Nitrogen of Clonal Offspring in Leymus Chinensis
Authors: Li Xiliang , Hu Ningning , Yin Jingjing , Ren Weibo , Fry Ellen
Published: February 2021

Aims Plants with a history of overgrazing show trait-mediated legacy effects. These legacy effects strongly influence growth dynamics and stress tolerance of grassland plants, thus impacting ecosystem functioning. Long-term overgrazing has strong effects on plant growth and carbon assimilation via asexual propagation. However, the links between nitrogen (N) cycling and grazing-induced plant legacy effects are largely unknown.Methods We tested the strength of legacy effects of long-term overgrazing on N metabolism in the clonal plant Leymus chinensis, and its associated changes at the physiological and molecular levels. These tests were conducted in both field and greenhouse experiments.Results The clonal offspring of overgrazed L. chinensis were significantly smaller than the control offspring, with lower individual N uptake and N utilization efficiency, indicating that the N dynamics were impacted by plant legacy effects. The response ratios of root traits to N patches in the clonal offspring of overgrazed L. chinensis were significantly higher than those of the control, indicating that root nutrient foraging plasticity increased to cope with grazing-induced N heterogeneity. Moreover, the observed plant legacy effects slightly decreased N absorbability in roots but significantly increased N assimilation capacity, by increasing N resorption efficiency in particular, with biotic stress memory activated at the enzymatic and transcriptional levels.Conclusions We propose that multigenerational exposure of perennial plants to herbivore foraging can produce a legacy effect on nutrient uptake, which offers insights into the potential resilience of grasslands to overgrazing.
Role of Nickel Doping on Magnetocaloric Properties of La0.7Sr0.3Mn1-xNixO3 Manganites
Authors: Çetin Selda Kılıç , Akça Gönül , Aslan Mehmet Selim , Ekicibil Ahmet
Published: February 2021

This study reports the effect of Ni substitution for Mn on structural, magnetic and magnetocaloric properties of La0.7Sr0.3MnO3 manganite synthesized by sol-gel technique. The structural, morphological and magnetic properties are investigated using x-ray diffractometer (XRD), scanning electron microscope (SEM) and vibrating sample magnetometer (VSM) systems. XRD results showed that all samples crystallize in rhombohedral structure. Thermomagnetic measurements showed that TC decreases with the addition of Ni from 363 K for x = 0.00 to 324 K for x = 0.06. ΔSM determined by Maxwell’s relations and Landau theory gave compatible results in the transition temperature and region above. ΔSMmax values were determined as 4.52, 4.51, 4.41 and 3.90 Jkg-1K-1 for x = 0.00, 0.02, 0.04 and 0.06 at 5T, respectively. The Arrott plots and the scaling analysis of ΔSM, which collapsed on a single curve, showed that magnetic transitions are second order.
How Does the Th1/Th2 Polarization in Milk Change According to the Types of Bacteria that Cause Subclinical Mastitis in Cows?
Authors: SAFAK Tarik , RISVANLI Ali , ASCI-TORAMAN Zulal
Published: February 2021

The authors have requested that this preprint be removed from Research Square.
Redox-induced Mobilization of Rare Earth Elements in Musa Estuary Sediment, Southwest of Iran
Authors: Madadi Reyhane , Saeedi Mohsen , Karbassi Abdolreza
Published: February 2021

In aquatic environments, metals tend to sink into sedimentary beds, but under different redox conditions they might be released to the water column. Oxic and anoxic microcosm experiments were conducted using an automatic microcosm apparatus to investigate how redox potential (Eh) affects the release of rare earth elements (REEs) in an estuary sediment sample. Results indicated that REEs mobility increases in both oxic and anoxic conditions although the average amount of REEs mobilization was higher in oxic conditions than anoxic conditions. Lu and Sm were the most mobile elements while Ce showed the lowest amount of release. REEs release is influenced by a mix of controlling factors including dissolution of Fe-Mn oxyhydroxides, low pH condition, and increase in dissolved organic carbon (DOC) under anoxic condition. An increase in Eh caused a decreasing pH from 8.08 to 6.80 and increasing DOC from 18.93 to 425 mg/l which resulted in the release of REEs. Enrichment factors (EFs) revealed that Musa estuary is threatened with Ce, Dy, La, Nd, Pr, and Sm. The high ecotoxicology effects of soluble REEs calling for potential environmental risks in Musa estuary.
Responsiveness and Convergent Validity of QLU-C10D and EQ-5D-3L in Assessing Short-Term Quality of Life Following Esophagectomy
Authors: Bulamu Norma B. , Vissapragada Ravi , Chen Gang , Ratcliffe Julie , Mudge Louise A. , Smithers Mark B , Isenring Elizabeth A. , Smith Lorelle , Jamieson Glyn G , Watson David I
Published: February 2021

Aim: This study assessed the responsiveness and convergent validity of two preference-based measures; the newly developed cancer-specific EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D) relative to the generic three-level version of the EuroQol 5 dimensions (EQ-5D-3L) in evaluating short-term quality-of-life outcomes/utilities after esophagectomy.Methods: Participants were enrolled in a multicentre 2×2 factorial randomised controlled trial to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with esophageal cancer. Quality-of-life was assessed seven days before and 42 days after esophagectomy. Standardized Response Mean and Effect Size were calculated to assess responsiveness. Ceiling effects for each dimension were calculated as the proportion of the best level responses for that dimension. Convergent validity was assessed using Spearman’s correlation and the level of agreement was explored using Bland–Altman plots. Regression analysis was performed to identify which demographic and clinical factors influenced quality of life. Results: Respondents were 164, predominantly male (81%) with mean age of 63 years. Quality-of-life significantly reduced on both measures with large effect sizes (>80), and greater mean difference on QLU-C10D. Ceiling effects were observed with social activities (86%), mobility (67%), anxiety (55%) and pain (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling effects were observed with emotional function (53%), physical function (16%), nausea (35%), sleep (31%), bowel problems (21%) and pain (20%). A strong correlation (r=0.71) was observed between EQ-5D-3L anxiety and QLU-C10D emotional function dimensions. Good agreement (3.7% observations outside the limits of agreement) was observed between the utility scores. Blood loss and blood transfusion predicted EQ-5D-3L utility while smoking and tumour length >3cm were predictive of QLU-C10D utility. Changes in QLQ-C30 dimensions of emotional function, role function and pain were predictive of changes in EQ-5D-3L utility while changes in physical, social and role function as well as all the symptom scales were predictive of change in QLU-C10D utility. Conclusion: Although there is strong agreement between utility scores, QLU-C10D was more sensitive to short-term utility changes following esophagectomy. Cognisant of requirements by policy makers to apply generic utility measures in cost effectiveness studies, disease-specific measures should be used alongside the generic measures. Trial registrationThe trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12611000178943) on the 15th February 2011.
Metabolic Profiling in Mice Infected with Echinococcosis
Authors: Zhu Mingxing , Du Xiancai , Xu Hongxia , Yang Songhao , Wang Chan , Zhu Yazhou , Zhang Tingrui , zhao wei
Published: February 2021

Background: Echinococcosis is a severe zoonotic parasitic disease, which seriously affects the health of the hosts. The diagnosis of echinococcosis depends on objective detection of clinical symptoms. However, the patient is often in the late stage of the disease when the symptoms appear, limiting the early diagnosis of echinococcosis. The treatment and prognosis of the patients are seriously hampered due to long-term asymptomatic latency. Metabolomics is a new discipline developed in the late 1990s. It reflects a series of biological responses in a pathophysiological process by demonstrating the changes in metabolism under the influence of internal and external factors. When the organism is invaded by pathogens, the alteration in characteristics of metabolites in cells becomes exceedingly sensitive. Here, we used a liquid chromatography with tandem mass spectrometry (LC-MS/MS) system-based metabolomics approach to determine the molecular mechanism of cystic echinococcosis (CE) and to develop an effective method for CE diagnosis. Methods: Eight-weeks-old female Balb/c mice were divided into normal and Echinococcus granulosus infection groups. To develop the Echinococcus granulosus infection model, mice were infected with protoscolex. Six weeks later, the abdomen of mice was obviously bulged. An LC-MS/MS system-based metabolomics approach was used for the analysis of the liver and feces to reveal the metabolic profiles of mice with echinococcosis. Results: We found that the metabolism of nucleotides, alkaloids, amino acids, amides, and organic acids in mice is closely interrelated with Echinococcus granulosus infectionConclusion: The metabolomics approach used in this study provides a reference for a highly sensitive and specific diagnostic and screening method for echinococcosis.
LncRNA SUMO1P3 Aggravates Doxorubicin-Induced Cardiomyocyte Apoptosis by Targeting miR-93-5p / Bin1
Authors: Lin Xuefeng , Ma Aiqun Ma
Published: February 2021

Background/AimsNon-coding RNA plays a critical role in myocardial apoptosis induced by doxorubicin (DOX). However, the specific function of Long noncoding RNA (lncRNA) small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is unclear. The purpose of this study was to determine the role of lncRNA SUMO1P3 in myocardial apoptosis induced by DOX. MethodsQRT-PCR were used to detect the expression levels of SUMO1P3 and miR-93-5p in DOX-treated primary cardiomyocytes and rat models. QRT-PCR and Western blot were used to detect the expression levels of Bin1 in DOX-treated primary cardiomyocytes and rat models. The relationship between SUMO1P3, miR-93-5p and Bin1 was analyzed using bioinformatics analysis and Luciferase reporter assay. The effects of DOX on the viability and apoptosis of cardiomyocytes were evaluated by flow cytometry and CCK-8. The effects of SUMO1P3 on cardiomyocyte apoptosis were analyzed by TUNEL staining and echocardiography. ResultsIn DOX-treated primary cardiomyocytes and rat models, the expression levels of SUMO1P3 and Bin1 were significantly increased, while the expression levels of miR-93-5p were significantly reduced. MiR-93-5p was a direct target gene of SUMO1P3, and Bin1 was a direct target gene of miR-93-5p. In addition, miR-93-5p reversed the protective effect of SUMO1P3 knockout on cardiomyocytes by inhibiting the expression of Bin1. ConclusionSUMO1P3 inhibited DOX-induced cardiomyocyte apoptosis through miR-93-5p/Bin1 axis.
Synthesis, Characterization, and Reaction of Divinyl-Substituted Laddersiloxanes
Authors: Liu Yujia , Endo Aimi , Zhang Peiyao , Takizawa Akira , Takeda Nobuhiro , Ouali Armelle , Unno Masafumi
Published: February 2021

Purpose Silsesquioxanes with well-defined structures have been of great interest recently because of their superior properties. Among them, laddersiloxanes (ladder-type silsesquioxanes with defined structure) were less explored because step-by-step synthesis is usually necessary. In order to investigate the properties of laddersiloxane, and apply these compounds to the monomers of high function materials, we prepared laddersiloxanes with reactive vinyl groups.MethodsThe target compounds were obtained in a two-step reaction from commercially available alkoxysilanes, and total yields were good. Three stereoisomers included in the products were fully investigated by spectroscopic methods and structures were determined. ResultsAs an extension of our previous research of constructing new laddersiloxanes, here we will describe the synthesis, characterization, and functionalization of novel divinyl-substituted laddersiloxanes. Further transformation of all products proceeded smoothly, and extended laddersiloxanes were obtained by hydrosilylation. One of the isomers was isolated and the structure was determined unequivocally by X-ray analysis. ConclusionThe laddersiloxanes described here have two reactive vinyl groups at each end of the molecule. Various reactions including hydrosilylation, polymerization, or olefin metathesis are possible, thus these compounds can be potential monomers for highly functionalized materials.
Driving after total knee and hip arthroplasty - an observational study from the perspective of rehabilitative orthopaedic therapy
Authors: Lazar Tiberiu-Adrian , Edelmann Martin , Awiszus Friedemann , Lohmann Christoph
Published: February 2021

Objective

Considering the legal stipulations in Germany regarding fitness to drive a motor vehicle, the aim of this study is to find out when patients with a TKA or THA actually take up driving again after surgery; how the replaced joint, side, gender, place of residence and physician’s recommendations, influences the patient in making the decision to start driving again.
Background

For a large proportion of the population, especially those residing in the countryside, the use of a car for daily activities is indispensable. Following a TKA or THA procedure, the overseeing physician will usually recommend refraining from driving, sometimes up to 12 weeks after surgery with a major social and economical impact on patient’s life.
Methods

92 eligible participants, contained within the frame of a prospective experimental observational study, were contacted via telephone 12 weeks after surgery and interviewed using a structured questionnaire. The answers were statistically analysed using SPSS®.
Discussion

There were statistically significant differences regarding operated side, gender and place of residence. Male patients drove in the 6th and 7th postoperative week, while female patients drove in the 8th and 9th postoperative week. For 58.6% of patients the reasoning for the first post-operative drive was medical: the journey to physiotherapy or to a doctor’s appointment. TKA impaired patients the most. Patients recovering from a TKA drive considerably later. Patients recovering from a right sided TKA have an increased risk by a factor of nine, not to become an “early driver”. Female patients who underwent TKA had an increased risk by a factor of 21, of becoming a “late driver”.
Conclusions

The rehabilitation following a right sided TKA proved a challenge with regard to the reuptake of driving. This should be taken into account when planning the course of therapy for patients who are regular drivers. Female patients could benefit from special training.
Trial registration:
DRKS00018693. Registered 20 September 2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018693
Andrographolide Promotes Proliferative and Osteogenic Potentials of Human Placenta-Derived Mesenchymal Stem Cells Through the Activation of Wnt/β-Catenin Signaling.
Authors: Phunikom Naruphong , Boonmeun Nittaya , Suksen Kanoknetr , Kheolamai Pakpoom , Manochantr Sirikul , Tantrawatpan Chairat , Tantikanlayaporn Duangrat
Published: February 2021

IntroductionThe in vitro expansion and differentiation of mesenchymal stem cells derived from bone marrow (BM-hMSCs) are considered as potential therapeutic tools for clinical applications in bone tissue engineering and regenerative medicine. However, invasive sampling and reduction in number and proliferative capacity with age are the major limitations of BM-hMSCs. Recently, human placenta-derived MSCs (PL-hMSCs) obtained by a non-invasive procedure have attracted much interest. Attempts to increase the potential of PL-hMSCs would be an important paradigm in regenerative medicine. Herein, we examined the proliferative and osteogenic effect of andrographolide (AP) on PL-hMSCs. MethodsMesenchymal stem cells were isolated from full-term normal human placentas and were characterized before using. Cell cytotoxicity and proliferative effect of AP were examined by MTT and BrdU assay, respectively. The non-toxicity concentrations of AP were further assessed for osteogenic effect determined by alkaline phosphatase (ALP) expression and activity, alizarin red staining, and osteoblast-specific gene expressions. Screening of genes involved in osteogenic differentiation related pathways modulated by AP were explored by a NanoString nCounter analysis. ResultsPL-hMSCs generated in this study met the MSCs criteria set by the International Society of Cellular Therapy. AP has no cytotoxic effect on PL-hMSCs up to 10 μM. The compound increased PL-hMSCs proliferation concomitant with increases in Wnt/ β-catenin level and activity. It also enhanced osteogenic differentiation in association with osteoblast-specific mRNA expression. Further, AP promoted bone formation and increased bone structural protein level, osteocalcin, in osteoblastic cells. Gene screening analysis showed the upregulation of genes related to Wnt/β-catenin, TGFβ/BMP, SMAD and FGF signaling pathways. ConclusionWe demonstrated, for the first time, the potential role of AP in promoting proliferation, osteogenic differentiation, and osteoblast bone formation of PL-hMSCs. This study suggests that AP may be an effective novel agent for the improvement of PL-hMSCs and stem cell-based therapy for bone regeneration.
Progressive Failure Analysis of Composite/aluminum Riveted Joint Subjected to Pull-through Loading
Authors: yang yuxing , Bao Yongjie , Liu Xueshu , Wang Jinlong , Du Fengming
Published: February 2021

The progressive failure mechanism of composite/aluminum riveted joint subjected to pull-through loading was investigated by experiments and finite element method. The pull-through tests were conducted and its load-displacement responses were analysed. A progressive damage model based on the Hashin-type criteria and zero-thickness cohesive zone method was developed by VUMAT subroutine, which was validated by both open-hole tensile test and three-point bending test. Load-displacement response, failure modes and damage propagation were analysed and compared with the experimental results. Major conclusions: 1) there are 4 obvious characteristic stages on the load-displacement curve: first load take-up stage, damage stage, second load take-up stage and failure stage; 2) relative error of stiffness, first load peak and second load peak between finite element method and experiments were 8.1%, -3.3% and 10.6%, respectively; 3) specimen was mainly broken by rivet-penetration fracture and delamination of plies of the composite laminate; 4) the material within the scope of the rivet head is more dangerous with more serious tensile damages than other regions, especially for 90° plies.
Ectopic Expression of a Novel Cold-resistance Protein 1 (BoCRP1) from Brassica Oleracea Promotes Tolerance to Cold via Modulating Stress Associated Components
Authors: Wani Umer Majeed , Sheikh Tahir Majeed , Raja Vaseem , Wani Zubair Ahmad , Jan Nelofer , Andrabi Khurshid Iqbal , John Riffat
Published: February 2021

Cold stress is considered as a major environmental factor that adversely affect the plant growth and distribution. Therefore, there arises an immediate need to cultivate effective strategies aimed at developing stress-tolerant crops that would boost the production and minimise the risks associated with cold stress. In this study, a novel cold-responsive protein1 isolated from Brassica oleracea (BoCRP1) was ectopically expressed in a cold susceptible tomato genotype Shalimar 1 and its function was investigated in response to chilling stress. BoCRP1 was constitutively expressed in all the tissues of B. oleracea including leaf, root and stem however, its expression was found to be significantly increased in response to cold stress. Moreover, transgenic tomato plants expressing BoCRP1 exhibited increased tolerance to chilling stress (4oC) with an overall improved rate of seed germination, increased root length, reduced membrane damage and increase in accumulation of osmoprotectants. Furthermore, we observed increased transcript levels of stress responsive genes and enhanced accumulation of ROS scavenging enzymes in transgenic on exposure to chilling stress. These results are therefore strongly in support of the role of BoCRP1 in offering the plant a protective shield and heightened resilience to chilling stress by maintaining osmotic balance, utilising the cellular antioxidant system and enhancing the transcription of cold responsive genes.
A Patient of Neurocysticercosis Misdiagnosed as Tuberculous Meningitis for 26 Years: a Case Report
Authors: Wang Yiyi , Guan Hongzhi , Liu Yuan , Lu Liandi , Li Qian , Yu-Zhao  , Zhen Xiaohan
Published: February 2021

Background: Neurocysticercosis (NCC) is a neurological infection caused by the larval stage of the tapeworm Taenia solium (T. solium). The diagnosis of NCC can be challenging because of heterogeneity in clinical manifestation. Neurocysticercosis is easily misdiagnosed as tuberculous meningitis (TBM).Case presentation: We describe a case of subarachnoid neurocysticercosis with 28 years illness course misdiagnosed as TBM for 26 years. The patient presented with symptoms of repeated headache, fever, serious low back and legs pain, and vomiting, occasional seizure and lose of consciousness. The neurological assessments revealed stiff neck and right plantar and saddle numbness. Lumbar puncture results revealed obvious intracranial hypertension, pleocytosis, elevated protein level, and decreased glucose level. Magnetic resonance imaging showed meningeal enhancement of brain, cystlike structure in the lumbosacral sac and the clumping of the nerve roots of the cauda equina. Five recurrent episodes occurred in twenty-eight years. TBM was considered as a probable etiology and was treated for tuberculosis empirically with adjunctive corticosteroids for 26 years. In the first three hospitalizations, During this period, the patient was hospitalized three times. In 2016, The local hypertrophic pachymeningitis were considered as a probable etiology. She was treated with steroid pulse therapy. At her fifth relapse, in 2018, next-generation sequencing of cerebrospinal fluid (CSF) identified the patient was NCC, T. solium infection. Her symptoms and CSF examination were relieved after etiological treatment. Conclusions: Neurocysticercosis is easily misdiagnosed as TBM. Meanwhile, adjunctive corticosteroids therapy can alleviate the symptom of TBM and NCC. So we suggest that NCC should be considered in the differential diagnosis of TBM. NGS of CSF is a promising tool for the diagnosis of NCC.
CMTM6 Promotes Migration, Invasion, and EMT by Interacting with and Stabilizing Vimentin in Hepatocellular Carcinoma Cells
Authors: Huang Xiaoting , Xiang Leyang , Wang Baiyao , Hu Jijie , Liu Chunshan , Ren Anbang , Du Kunpeng , Ye Gengtai , Liang Yingying , Tang Yunqiang , Yang Dinghua , Yuan Yawei
Published: February 2021

BackgroundCKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been associated with the development in many kinds of cancers. However, the roles of CMTM6 in hepatocellular carcinoma (HCC) are largely unknown. Thus, the present study aimed to investigate the function of CMTM6 in HCC.MethodsWe analysed CMTM6 levels and functions using human HCC cell lines, paired HCC and adjacent non-tumorous tissues, and a tissue microarray. CMTM6 expression was silenced using short hairpin RNAs and its was overexpressed from a lentivirus vector. CMTM6 mRNA and protein levels were determined using quantitative real-time reverse transcription PCR and western blotting, respectively. Proliferation, colony formation, migration, and invasion were assessed using a Cell counting kit-8, colony formation, wound-healing, and Matrigel invasion assays, respectively. Immunohistochemistry was used to score the expression of CMTM6 in tissue samples. The localization and binding partners of CMTM6 were investigated using immunofluorescence and coimmunoprecipitation experiments, respectively. A mouse xenograft model was used for in vivo studies.ResultsCompared with that in adjacent, non-cancerous tissue, Here, CMTM6 levels were increased in HCC tissue samples. Silencing of CMTM6 suppressed the proliferation, migration, and invasion of HCC cells. Conversely, CMTM6 overexpression enhanced HCC cell invasion, migration, and proliferation. Mechanistically, CMTM6 physically interacts with and stabilizes vimentin, thus inducing epithelial–mesenchymal transition (EMT), which promotes proliferation, migration and invasion. Importantly, in HCC tissues, CMTM6 expression correlated positively with vimentin levels. Poor prognosis of HCC was associated significantly with higher CMTM6 expression. ConclusionsCMTM6 has an important function in HCC proliferation, migration, and invasion, via its interaction with and stabilization of vimentin. CMTM6 might represent a potential biomarker and therapeutic target to treat HCC.
Application Effect Analysis of Three Methods of Heating and Humidification for Weaning Patients in ICU
Authors: Wu Yongxing , Bai Jiyu , Zhu XingQing , Zhu Zhijing
Published: February 2021

Objectives To investigate the effects of artificial nose, Venturi device+thermostatic humidification T-tube, Venturi device+thermostatic humidification T-tube+PEEP valve in patients with tracheotomy in ICU.Design: Cohort study.Setting: Tertiary academic medical center.Patients: A total of 215 patients were engaged in this study. Clinical and laboratory examination data were used to determine the heating and humidification efficiency of 3 different methods.Methods: We conducted randomized controlled trial. Patients who successfully weaned from mechanical ventilation were enrolled, and every patient was randomized to receive one of the above three interventions. Three groups of patients were compared in terms of vital signs, the effect of artificial airway heating and humidification, and blood gas indicators. Basic patient data (age, gender, mechanical ventilation duration, ICU stay, disease type) were recorded. Vital signs include heart rate, blood pressure, respiratory rate, oxygen saturation; The effect of heating and humidifying the artificial airway were defined as the number of sputum suction and coughing within 24 hours, sputum characteristics, whether there is bloody sputum formation, whether there is phlegm callus formation; Blood gas indicators include pH, oxygen partial pressure, carbon dioxide partial pressure, lactic acid, residual base, and bicarbonate.Results: In terms of the heating and humidification effect of patients in ICU, the heating and humidification effect of the Venturi device+T-tube method and the Venturi device+the T-tube +PEEP valve method were significantly superior to those of artificial nasal method (sputum suction number: P =0.0001; sputum scab: P =0.03; Number of cough: P =0.007).SpO2 was significantly higher (P =0.004) in the Venturi device+T tube+PEEP valve than that in the Venturi device+T tube.Conclusion: Compared with the artificial nose method, the T-piece+venturi device and thermostatic heating and humidifying T-tube +PEEP valve method is better. In terms of improving oxygenation, the Venturi device and the thermostatic humidification T tube +PEEP valve could improve the patient's oxygen sum more than the Venturi device and the thermostatic humidification T tube.
Centers and limit cycles for a generalized kukles differential systems of degree 8
Authors: Damene Loubna , Benterki Rebiha
Published: February 2021

In this paper we provide all the global phase portraits of the generalized kukles differential systems x= y; y = x + ax8 + bx6y2 + cx4y4 + dx2y6 + ey8; symmetric with respect to the x{axis, with a2 + b2 + c2 + d2 + e2 6= 0, and by using the averaging theory up to seven order, we give the upper bounds of limit cycles which can bifurcate from its center when we perturb it inside the class of all polynomial differential systems of degree 8. The main tool used for proving these results is based in the first integrals of the systems which form the discontinuous piecewise differential systems.
In Vivo Characterization and Genome-based Approach to Lactobacillus Johnsonii Byun-jo-01 and Its Probiotic Properties
Authors: Kim Dongjun , Cho Mun-ju , Lee Yongjun , Kil Eui-Joon , Byun SungJune , Lee Sukchan
Published: February 2021

To develop new antiviral probiotics, bacteria were isolated from the microbiome in a murine intestine. In 16S rDNA sequence analysis, most isolates were identified as Lactobacillus johnsonii. These isolates were further assessed using whole-genome sequencing through the Illumina and PacBio platform, which revealed that the isolates were new strains. A novel probiotic strain, Lactobacillus johnsonii Byun-jo-01, was evaluated to determine its probiotic characteristics of safety, immune modulation, and antiviral efficacy against murine norovirus. Oral administration of L. johnsonii Byun-jo-01 was demonstrated to be safe in mice in terms of body weight, food intake, and bacterial translocation. Additionally, the expression levels of IFN-beta and IFN-gamma induced by L. johnsonii Byun-jo-01 in the small intestines of mice were higher than those in mice fed L. paracasei ATCC 334 and L. reuteri KACC 11452. Among the three different bacterial strains used in this study, L. johnsonii Byun-jo-01 showed the highest antiviral efficacy against murine norovirus, reducing the viral titer in fecal samples by 28 times compared with mice infected with murine norovirus. To support those in vivo experiments, genome-based data mining was performed to investigate which genes related to probiotic-specific markers were highly expressed in this isolate. Specifically, DnaK, GroEL, GroES, and GrpE, which are involved in the acid adaptation required to overcome the harsh in vivo condition, were highly expressed. Taken together, these results suggest that host-originated probiotics can be more effective than bacteria isolated from other sources, such as fermented food.
The Synovium of Human Osteoarthritic Joints Retains Its Chondrogenic Potential Irrespective of Age
Authors: Hunziker Ernst Bruno , Shintani Nahoko , Haspl Miroslav , Lippuner Kurt , Vögelin Esther , Keel Marius JB
Published: February 2021

The autologous synovium is a potential tissue source for local induction of chondrogenesis by tissue engineering approaches to repair articular cartilage defects such as they occur in osteoarthritis. It was the aim of the present study to ascertain whether the aging of osteoarthritic patients compromises the chondrogenic potential of their knee-joint synovium.The patients were allocated to one of the following two age categories: 54 - 65 years and 66 - 86 years (n = 7-11 donors per time point and per experimental group). Synovial biopsies were induced in vitro to undergo chondrogenesis by exposing them to either bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of the two growth factors for up to 6 weeks. The differentiated explants were evaluated histomorphometrically for the volume fraction of metachromasia (sulfated proteoglycans), immunohistochemically for type-II collagen, and for the gene-expression levels of anabolic chondrogenic markers as well as catabolic factors by a real-time polymerase-chain-reaction (RT-PCR) analysis.Quantitative metachromasia revealed that chondrogenic differentiation of human synovial explants was induced to the greatest degree by either BMP-2 alone or the BMP-2/TGF-b1 combination, i.e. to a comparable level with each of the two stimulation protocols and within both age categories. The gene-expression levels of the anabolic chondrogenic markers confirmed the superiority of these two stimulation protocols and demonstrated the hyaline-like qualities of the generated cartilaginous matrix. The gene-expression levels of the catabolic markers were extremely low.Our data reveal the chondrogenic potential of the human knee-joint synovium of osteoarthritic patients to be uncompromised by ageing and catabolic processes. The potential of synovium-based clinical engineering (repair) of cartilage tissue using autologous synovium may thus not be reduced by the age of the human patient.
Clinical Profile of Migraine Headache Patients: a Descriptive Study of a Single Tertiary Centre in Malaysia
Authors: Lau Yue Hui , Kurien Jessica K , Lau Keng Ming , Adenan Sufian
Published: February 2021

Background:Migraine is one of the most common disabling neurological disorder among adult population in Malaysia. Purpose:To evaluate demographic characteristics among the migraine patients.Methods:A total of 73 patients with the complain of headache, who aged 18 to 65 were recruited prospectively at neurology clinic from December 2017 to April 2019 in Kuala Lumpur Hospital. All new patients were mainly referred by primary care clinics. Demographic characteristics such as age and gender, age of onset, clinical phenotypes, trigger factors, rescue therapy, prophylaxis usage, frequency of headache, psychiatric symptoms, marital status and education level were all evaluated. Migraine headaches were coded according to ICHD-III criteria. Statistical analysis was analysed using SPSS software. Descriptive statistics, mean and standard deviation were used to evaluate for clinical data.Results:44 out of 73 patients had migraine (60.3%). The mean age of migraine patients was 30 and mean age of onset was 24.8. Majority of the sample were female (36, 81.8%), single (23.52.3%) and with tertiary education level (31, 70.5%). The most frequent symptoms included unilateral headache (36, 81.8%) with throbbing in quality (39, 88.6%). The main trigger factor was stress (23, 52.3%). The most frequently used rescue therapies are sleeping and paracetamol ingestion (18, 40.9%). Most of the patients experienced acute attack 4-14 days in a month (15, 34.1%). 42(95.5%) patients were prophylaxis naïve.Conclusion:Characteristics of the migraine patients in Kuala Lumpur Hospital are comparable with previous studies. A registry of headache patients is crucial to determine the prevalence and local impact of the disease in Malaysia.