bluuebunny/crossref_metadata_2025 huggingface dataset:
Zircon provenance of Quaternary cover beds using U–Pb dating: Regional differences in the Southwestern USA
Authors: Richter‐Krautz Jana , Hofmann Mandy , Zieger Johannes , Linnemann Ulf , Kleber Arno
Published: January 2021

U–Pb dating of detrital zircons (DZ) in Quaternary slope deposits (cover beds) and examination of the surface structure of single zircon grains may enable reconstruction of the provenance of their aeolian components and help to reconstruct sedimentary palaeo‐transportation cascades. We distinguish several layers of slope deposits (cover beds) using a palaeosol‐supported sequence‐stratigraphic approach. In a pilot study, we demonstrate the usability of using end‐member‐modelled analyses of grain sizes to identify the aeolian matter, multi‐dimensional scaling and density functions (probability density functions (PDF) and Kernel density estimations (KDE)) of the U–Pb data, and the grain morphology of DZ, and show that the age and appearance variation of DZ in the Great Basin differ remarkably from those of the Colorado Plateau.

All samples contain aeolian matter. Density functions of the DZ ages show similarities within each of the two regions. The Great Basin samples are dominated by late Cretaceous and Paleogene zircons, which are assumed to derive from volcanism. In contrast, the Colorado Plateau samples are almost free of these contributions. Presumably, the difference is due to palaeolakes, which were frequent in the Great Basin only, whose sediments contain a similar spectrum of DZ ages. Zircon morphology indicates that most grains have a history of aeolian transportation, whereas the grains assumed to be of volcanic origin often do not show similar transportation marks; this indicates that their transportation was dominated by the eruptive process but fewer steps of a transportation cascade. Multidimensional scaling of age data defines clusters of samples with similar DZ ages and – compared with published ages from possible sources – allows first interpretations of provenance.

Quaternary aeolian sediments have not been studied in, and the applied mix of methods has not been applied to, the southwestern USA before. We demonstrate their feasibility for this study area.
Blockchain technology for energy‐aware mobile crowd sensing approaches in Internet of Things
Authors: Sisi Zhu , Souri Alireza
Published: January 2021

Today, Blockchain technology is emerging to support high secured performance computing. To improve privacy and security factors of allocate, storage, and manage resources in edge computing, blockchain technology can be used to guarantee safe data transmission and communications in Internet of Things (IoT). Due to heterogeneity of resources to cover a range number of IoT applications, resource allocation has a key role for increasing performance of the IoT systems in edge computing. Also, a blockchain‐based resource allocation model can support Quality of Service (QoS) for IoT applications to ensure a high secured communication environment in edge computing. This paper reviews different existing green energy strategies based on blockchain technology in mobile crowd sensing. Mobile crowd sensing refers to all computational aspects related to smart city, smart home‐care, smart grid, smart transportations, smart medical systems, smart industry, manufacturing, and smart farming in IoT environments. This review aims to classify principles and technical aspects of green energy strategies based on blockchain technology in mobile crowd sensing with respect to technical aspects, applied algorithms, evaluation factors, and evaluation environments. Based on Systematic Literature Review (SLR), we selected 37 high potential and key relevant research studies to consider in this review. Based on analytical results, 35% of them were considered as private‐based blockchain methods, 33% of them were applied to the public‐based blockchain methods, 24% of them were considered as consortium‐based blockchain methods, and 8% of them were as hybrid‐based blockchain methods.
Elevated temperature thermal properties of advanced materials used in LSF systems
Authors: Gnanachelvam Sayilacksha , Mahendran Mahen , Ariyanayagam Anthony
Published: January 2021

Lightweight cold‐formed steel (CFS) construction solutions are increasingly adopted in low and mid‐rise buildings. Many different materials are used to construct CFS wall systems, without a full understanding of their thermal properties. For many of these materials, only ambient temperature thermal properties are available from their manufacturers. This creates difficulty in classifying the materials for use at elevated temperatures. In this study, a series of elevated temperature thermal property tests to measure specific heat, thermal conductivity, and mass loss was conducted for a range building materials from wallboards, insulation, and phase‐change materials (PCMs), used in Australia and several other countries. Simultaneous Thermal Analyser and Laser Flash Apparatus were used to determine the elevated temperature thermal properties of the selected materials, gypsum plasterboard, PCM incorporated gypsum plasterboard, magnesium sulphate board, fibre cement board, cellulose insulation, vacuum insulation panel, microencapsulated paraffin PCM, and bio‐based PCM. Their elevated temperature thermal properties are presented in this article, which also includes analyses of their chemical composition and associated chemical reactions at elevated temperatures. These results can be used in the selection of suitable energy‐efficient and fire‐resistive materials, and in heat transfer modeling to identify wall configurations with increased fire resistance and energy efficiency.
Genome‐wide association study in diverse Iranian wheat germplasms detected several putative genomic regions associated with stem rust resistance
Authors: Saremirad Ali , Bihamta Mohammad Reza , Malihipour Ali , Mostafavi Khodadad , Alipour Hadi
Published: January 2021

Stem rust is one of the most important diseases, threatening global wheat production. Identifying genomic regions associated with resistance to stem rust at the seedling stage may contribute wheat breeders to introduce durably resistant varieties. Genome‐wide association study (GWAS) approach was applied to detect stem rust (Sr) resistance genes/QTLs in a set of 282 Iranian bread wheat varieties and landraces. Germplasms evaluated for infection type and latent period in four races of Puccinia graminis f. sp. tritici (Pgt). A total of 3 QTLs for infection type (R2 values from 9.54% to 10.76%) and 4 QTLs for the latent period (R2 values from 8.97% to 12.24%) of studied Pgt races were identified in the original dataset. However, using the imputed SNPs dataset, the number of QTLs for infection type increased to 10 QTLs (R2 values from 8.12% to 11.19%), and for the latent period increased to 44 QTLs (R2 values from 9.47% to 26.70%). According to the results, the Iranian wheat germplasms are a valuable source of resistance to stem rust which can be used in wheat breeding programs. Furthermore, new information for the selection of resistant genotypes against the disease through improving marker‐assisted selection efficiency has been suggested.
Nutritional impact of adding a serving of mushrooms on usual intakes and nutrient adequacy using National Health and Nutrition Examination Survey 2011–2016 data
Authors: Fulgoni Victor L. , Agarwal Sanjiv
Published: January 2021

To evaluate the nutritional impact of adding a serving of mushrooms on usual intakes and population adequacy of nutrients the National Health and Nutrition Examination Survey (NHANES) 2011–2016 dietary data for 9–18 years and 19+ years and a composite of commonly consumed raw mushrooms as well as oyster mushrooms (nutrient profiles from USDA data) were used for modeling. Usual intakes of nutrients and the percent population below the Estimated Average Requirement (EAR) or above the Adequate Intake (AI) were estimated before and after addition of mushrooms. Means with nonoverlapping 95th percentile confidence levels were used to assess meaningful differences. Addition of a serving (84 g) of mushrooms to the diet resulted in an increase in dietary fiber (5%–6%), copper (24%–32%), phosphorus (6%), potassium (12%–14%), selenium (13%–14%), zinc (5%–6%), riboflavin (13%–15%), niacin (13%–14%), and choline (5%–6%) in both adolescents and adults; and in iron (2.32%), thiamin (4.07%), folate (3.66%), and vitamin B6 (4.64%) in adults only, but had no impact on energy, carbohydrate, fat, or sodium. Addition of a serving of mushrooms also decreased the % below EAR for copper, phosphorus, and riboflavin for those 9–18 years and for copper, phosphorus, selenium, zinc, thiamine, riboflavin, niacin, folate, and vitamin B6 for those 19+ years and increased the % above AI for potassium for both age groups. Addition of oyster mushrooms additionally increased 12%–13% vitamin D, and 12%–15% choline in the NHANES 2011–2016 diets. Addition of mushrooms exposed to UV light to increase vitamin D levels to 5 µg/serving also almost doubled vitamin D intake (98%–104%) and decreased inadequacy. Addition of a serving of mushrooms would also add 2.2 mg ergothioneine and 3.5 mg glutathione to the diet. Addition of a mushroom serving to the diet would increase several micronutrients including shortfall nutrients, without having any impact on energy, sodium, or fat.
Partnerships in Innovation and Market Development: The Path Forward
Authors: DeCotis Paul A.
Published: January 2021

Government support for energy research and development has been critically important in advancing many of the products and technological breakthroughs that are commonplace in the industry today. For decades, federal and state tax and fiscal policies have supported and helped drive down the cost of many products and innovations. Easily recognizable examples include government and private partnership support in development of nuclear power for commercial power generation, hydraulic fracking for increasing domestic natural gas production, and wind turbine design, materials, and manufacturing and solar panel innovations that today make these wind and solar technologies cost‐competitive in certain applications and circumstances. Other examples include alternative fuel vehicle research and demonstration including hydrogen, hybrid, and electric vehicles for passenger and light and heavy‐duty vehicles. Federal and state support for research, development, and demonstration (RD&D) coupled with private investment has significantly driven down the costs of energy storage and brought about new chemical compositions, breakthroughs in materials science, and battery designs. Tax policy has and continues to support exploration and extraction of fossil fuels as well.
Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography
Authors: Casula Elias Paolo , Pellicciari Maria Concetta , Bonnì Sonia , Spanò Barbara , Ponzo Viviana , Salsano Ilenia , Giulietti Giovanni , Martino Cinnera Alex , Maiella Michele , Borghi Ilaria , Rocchi Lorenzo , Bozzali Marco , Sallustio Fabrizio , Caltagirone Carlo , Koch Giacomo
Published: January 2021

Interhemispheric interactions in stroke patients are frequently characterized by abnormalities, in terms of balance and inhibition. Previous results showed an impressive variability, mostly given to the instability of motor‐evoked potentials when evoked from the affected hemisphere. We aim to find reliable interhemispheric measures in stroke patients with a not‐evocable motor‐evoked potential from the affected hemisphere, by combining transcranial magnetic stimulation (TMS) and electroencephalography. Ninteen stroke patients (seven females; 61.26 ± 9.8 years) were studied for 6 months after a first‐ever stroke in the middle cerebral artery territory. Patients underwent four evaluations: clinical, cortical, corticospinal, and structural. To test the reliability of our measures, the evaluations were repeated after 3 weeks. To test the sensitivity, 14 age‐matched healthy controls were compared to stroke patients. In stroke patients, stimulation of the affected hemisphere did not result in any inhibition onto the unaffected. The stimulation of the unaffected hemisphere revealed a preservation of the inhibition mechanism onto the affected. This resulted in a remarkable interhemispheric imbalance, whereas this mechanism was steadily symmetric in healthy controls. This result was stable when cortical evaluation was repeated after 3 weeks. Importantly, patients with a better recovery of the affected hand strength were the ones with a more stable interhemispheric balance. Finally, we found an association between microstructural integrity of callosal fibers, suppression of interhemispheric TMS‐evoked activity and interhemispheric connectivity. We provide direct and sensitive cortical measures of interhemispheric imbalance in stroke patients. These measures offer a reliable means of distinguishing healthy and pathological interhemispheric dynamics.
Impact assessment of anthropogenic activities on the ecological systems in the Xiongan New Area in the North China Plain
Authors: Ma Rong , Li Lei , Zhang Bing
Published: January 2021

The aim of this study is to assess the impact of anthropogenic activities on the ecological systems in the Xiongan New Area (XNA), China. Artificial sweeteners (ASs) were used as anthropogenic tracers to investigate how anthropogenic activities affect water, soil, and plant layers. For this purpose, the concentrations of 4 typical ASs, acesulfame (ACE), sucralose (SUC), saccharin (SAC), and cyclamate (CYC) were measured in water, soil, and plant layers. Moreover, a tracer test was conducted in the critical zone observatory (CZO) in the southern part of the study area to investigate the migration path and time of anthropogenic activities on the ecological systems. Acesulfame, SUC, SAC, and CYC were widely detected in all of the sample types, and their average values were 0.22, 0.53, 0.06, and 0.08 µg/L in the water layer; 0.04, 0.18, 0.06, and 0.06 µg/kg in the soil layer; and 1.79, 0.11, 4.42, and 0.95 µg/kg in the plant layer, respectively. The tracer test showed that 1.1% to 1.8% of the impacts of the anthropogenic activities migrated from the surface to the shallow aquifer within 13 d, 6% to 19% migrated to the maize layer within 28 d, and 79% to 93% were adsorbed and biodegraded in the soil layer. Therefore, the scope and strength of the influence of the anthropogenic activities on the environmental media exhibit a decreasing sequence of maize > water > soil. This study not only quantitatively characterizes the impact of anthropogenic activities on the ecological environment but also presents the first comprehensive overview of the environmental fate of ASs in the critical zone of the XNA, China. Integr Environ Assess Manag 2021;17:866–876. © 2021 SETAC
DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
Authors: Thuijs Nikki B. , Berkhof Johannes , Özer Müjde , Duin Sylvia , van Splunter Annina P. , Snoek Barbara C. , Heideman Daniëlle A. M. , van Beurden Marc , Steenbergen Renske D. M. , Bleeker Maaike C. G.
Published: January 2021

Current clinical and histological classifications are unable to determine the risk of vulvar squamous cell carcinoma (VSCC) in high‐grade vulvar intraepithelial neoplasia (VIN), making prognostic biomarkers highly needed. We studied host‐cell DNA methylation markers in high‐grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN) without VSCC, in HSIL and dVIN adjacent to VSCC and in human papillomavirus (HPV) positive and negative VSCC, relative to control vulvar tissues. A series of 192 formalin‐fixed paraffin‐embedded vulvar samples, including VSCC (n = 58), VIN adjacent to VSCC (n = 30), VIN without VSCC during follow‐up (n = 41) and normal vulvar tissues (n = 63), were tested for 12 DNA methylation markers with quantitative multiplex methylation‐specific PCR (qMSP). HPV status was determined by p16INK4A immunohistochemistry and high‐risk HPV PCR analysis. Logistic regression analyses were used to determine methylation patterns and methylation marker performance for VIN and VSCC detection. Methylation markers showed significantly higher methylation levels with increasing severity of disease. VIN adjacent to VSCC showed a similar methylation‐high pattern as VSCC, while VIN without VSCC displayed a heterogeneous methylation pattern. Vulvar carcinogenesis is associated with increased DNA methylation. Higher DNA methylation levels in VIN seem to reflect higher cancer risk, emphasizing the high potential of DNA methylation biomarkers in the diagnostic workup of VIN. As a next step, longitudinal studies are needed to verify the prognostic value of methylation biomarkers as a clinical tool for stratification of cancer risk in women with VIN.
International trade and economic growth: The role of institutional factors and ethnic diversity in sub‐Saharan Africa
Authors: Coulibaly Romaric Gninlgonakan
Published: January 2021

The aim of this article is to analyse the role of trade on sub‐Saharan countries growth considering the effect of governance and ethnic diversity. We start by the framework of the augmented Solow growth model in which we include a set of control variables like trade as openness measure. The estimated model uses Pooled Mean Group technique on a sample of 44 countries of sub‐Saharan Africa during 1980–2017. It emerges that trade has a positive and significant influence on per capita income in the sub‐Saharan zone. This positive effect can also be empowered by improving the level of governance and by ethnic fragmentation. This fact shows the importance of a good political governance and the mastering of trade policies to gain more from trade openness for these countries.
Clinical presentations, pregnancy complications, and maternal outcomes in pregnant women with COVID‐19 and tuberculosis: A retrospective cohort study
Authors: Gajbhiye Rahul K. , Mahajan Niraj N. , Kamath Neha , Bahirat Shubhada , Patokar Gauri , Bhurke Aishwarya V. , Modi Deepak N. , Mahale Smita D.
Published: January 2021

Pregnant women with symptomatic COVID‐19 should also be tested for TB in countries with a high burden of TB. The infrastructure of the TB Program can be utilized for the control of COVID‐19, and vice versa.
Systems Engineering the Conditions of the Possibility (Towards Systems Engineering v2.0)
Authors: Willett Keith D.
Published: January 2021

Traditional systems engineering's focus is on cause and effect. When we turn a wheel, pull a lever, or flip a switch we expect a certain outcome. This is a rules‐based approach where stimulus‐response is deterministic in a well‐defined, well‐bounded, finite, and predominantly static system. If anything deviates from the expected, simple systemic structures (logic gates) or simple rules (if‐then‐else) provide optional preplanned action. Human intervention provides the intelligence and action necessary for dynamic adjustment to a negative event (adversity, avoid loss) or detecting and dynamically adjusting to a positive event (opportunity, seek gain). The now and future discipline of systems engineering (systems engineering v2.0) has the tools to transcend cause‐effect and effectively embrace the nondeterministic, flexibly defined, blurred‐boundaries, highly combinatorial if not infinite, and adaptability. Systems engineers can design solutions to adapt to predictable and unpredictable change for the system to remain viable while encountering adversity (loss‐driven) and relevant when threatened by obsolescence (opportunity‐driven). In addition to cause and effect, systems engineering v2.0 is systems engineering the conditions of the possibility.

This paper does not intend to provide answers, but provides a framework for discerning better questions and eliciting research in the many technical areas providing continual dynamic adaptation of complex socio‐technical systems of systems. Realizing systems engineering v2.0 will come from the hard work of many over years. We are already on the way with this being one more step toward formalizing a new discipline.
Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology
Authors: Teng Wenqi , Yang Zhaogang , Wang Suiping , Xiong Di , Chen Yifei , Wu Zhimin
Published: January 2021

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA‐15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA‐15 indicates that SBA‐15 has high biocompatibility. Fibrous SBA‐15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA‐15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA‐15 types significantly increased Kruppel‐like factor 2 (KLF2) protein, irregular SBA‐15 (1), non‐aggregated spherical SBA‐15 (2) and aggregation The spherical SBA‐15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA‐15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO‐eNOS pathway, but the irregular spherical SBA‐15 reduces the eNOS modifier KLF4. The rod‐shaped SBA‐15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.
Wnt16 Elicits a Protective Effect Against Fractures and Supports Bone Repair in Zebrafish
Authors: McGowan Lucy M , Kague Erika , Vorster Alistair , Newham Elis , Cross Stephen , Hammond Chrissy L
Published: January 2021

Bone homeostasis is a dynamic, multicellular process that is required throughout life to maintain bone integrity, prevent fracture, and respond to skeletal damage. WNT16 has been linked to bone fragility and osteoporosis in human genome wide‐association studies, as well as the functional hematopoiesis of leukocytes in vivo. However, the mechanisms by which WNT16 promotes bone health and repair are not fully understood. In this study, CRISPR‐Cas9 was used to generate mutant zebrafish lacking Wnt16 (wnt16−/−) to study its effect on bone dynamically. The wnt16 mutants displayed variable tissue mineral density (TMD) and were susceptible to spontaneous fractures and the accumulation of bone calluses at an early age. Fractures were induced in the lepidotrichia of the caudal fins of wnt16−/− and WT zebrafish; this model was used to probe the mechanisms by which Wnt16 regulates skeletal and immune cell dynamics in vivo. In WT fins, wnt16 expression increased significantly during the early stages for bone repair. Mineralization of bone during fracture repair was significantly delayed in wnt16 mutants compared with WT zebrafish. Surprisingly, there was no evidence that the recruitment of innate immune cells to fractures or soft callus formation was altered in wnt16 mutants. However, osteoblast recruitment was significantly delayed in wnt16 mutants postfracture, coinciding with precocious activation of the canonical Wnt signaling pathway. In situ hybridization suggests that canonical Wnt‐responsive cells within fractures are osteoblast progenitors, and that osteoblast differentiation during bone repair is coordinated by the dynamic expression of runx2a and wnt16. This study highlights zebrafish as an emerging model for functionally validating osteoporosis–associated genes and investigating fracture repair dynamically in vivo. Using this model, it was found that Wnt16 protects against fracture and supports bone repair, likely by modulating canonical Wnt activity via runx2a to facilitate osteoblast differentiation and bone matrix deposition. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked
Authors: Stavnichuk Mariya , Tauer Josephine T , Nagy Zoltan , Mazharian Alexandra , Welman Mélanie , Lordkipanidzé Marie , Senis Yotis A , Komarova Svetlana V
Published: January 2021

Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b−/−) mice. Although male and female Mpig6b−/− mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b−/− mice developed progressive splenomegaly starting at 8 weeks of age. Micro–computed tomography (μCT) of femurs showed that female Mpig6b−/− mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b−/− mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16 weeks. Ovariectomy of 10-week-old female Mpig6b−/− mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b−/− mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b−/− mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b−/− mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
miR‐101‐loaded exosomes secreted by bone marrow mesenchymal stem cells requires the FBXW7/HIF1α/FOXP3 axis, facilitating osteogenic differentiation
Authors: Li Yanhong , Wang Jing , Ma Yanchao , Du Wenjia , Feng Kai , Wang Shuanke
Published: January 2021

Exosomes derived from mesenchymal stem cells (MSCs) have emerged as significant mediators of intercellular communication, with studies highlighting their role in the transmission of biological signals between cells. Dominant microRNA (miRNA)‐mediated translational repression of messenger RNAs has been extensively investigated in regard to its influence in orchestrating osteogenic differentiation. In the current study, we sought to ascertain the contributory role of miRNA‐101 (miR‐101) encapsulated in the process of bone marrow mesenchymal stem cell (BMSC)‐derived exosomes in osteogenic differentiation. Exosomes were initially extracted from BMSCs at Days 0, 3, 12, and 21 of osteogenic differentiation by ultracentrifugation. Artificial modulation of miR‐101 and FBXW7 (silencing and overexpression) were performed in the BMSCs to identify its effects on osteogenic factors, alkaline phosphatase activity, and osteogenic differentiation. Mechanistic exploration was performed to evaluate the binding affinity between miR‐101 and FBXW7, the FBXW7‐mediated HIF1α ubiquitination, and the HIF1α enrichment in the FOXP3 promoter region. Exosomes from MSCs in the late stage of osteogenic differentiation exhibited enhanced osteogenic differentiation. Upregulated miR‐101 in MSC‐derived exosomes was detected during osteogenic differentiation, while diminished levels of FBXW7 expression was noted. Importantly, miR‐101 was found to specifically bind to the 3′‐untranslated region of FBXW7. Meanwhile, data was obtained indicating that FBXW7 could ubiquitinate and degrade HIF1α to repress its upregulation during osteogenic differentiation. HIF1α bound to the promoter region of FOXP3 to facilitate osteogenic differentiation. Ultimately, the findings of the current study demonstrate that BMSC‐derived exosomal miR‐101 augments osteogenic differentiation in MSCs by inhibiting FBXW7 to regulate the HIF1α/FOXP3 axis.
A novel strategy for engineering of a smart generation of immune ribonucleases against EGFR+ cells
Authors: Taghizadegan Nooshin , Firoozrai Mohsen , Nassiri Mohammadreza , Ariannejad Hamid
Published: January 2021

The overexpression of epidermal growth factor receptor (EGFR) could result in the development of solid tumors of prostate, breast, gastric, colorectal, ovarian, and head and neck, leading to carcinoma. Antibody therapies are ideal methods to overcome malignant diseases. However, immunoribonucleases are a new generation of antibodies in which an RNase binds to a specific antibody and shows a stronger ability to terminate cancer cells. In this study, we engineered Rana pipiens RNase to bind to the scFv of human antiepidermal growth factor receptor antibody. The molecular dynamic simulations confirmed protein stability and the ability of scFv−ranpirnase (rantoxin) to bind to epidermal growth factor receptor protein. Then, the rantoxin construct was synthesized in a pCDNA 3.1 Neo vector. CHO‐K1 cells were used as expression hosts and the construct was transfected. Cells were selected by antibiotic therapies using neomycin, 120 mg/ml, and the high‐yield colony was screened by real‐time polymerase chain reaction (PCR) methods. Then, the recombinant protein production was confirmed using the sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot analyses. The molecular dynamic simulation (MDS) confirmed that the I467, S468, Q408, and H409 amino acids of EGFR bonded well to rantoxin. As revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) and western blot analyses, the rantoxin production and PCR analysis showed that the T3 colony can produce rantoxin messenger RNA fourfold higher than the GAPDH gene. The immunotoxin function was assessed in A431 cancer cells and EGFR‐negative HEK293 cells, and IC50 values were estimated to be 22.4 ± 3 and >620.4 ± 5 nM, respectively. The results indicated that the immunotoxins produced in this study had the potential for use as anticancer drugs.
Silencing of long noncoding RNA MYLK‐AS1 suppresses nephroblastoma via down‐regulation of CCNE1 through transcription factor TCF7L2
Authors: Zhu Shibo , Zhang Jingqi , Gao Xiaofeng , Tang Xiangliang , Cui Yanhong , Li Dian , Jia Wei
Published: January 2021

Nephroblastoma, a pediatric kidney cancer, caused by pluripotent embryonic renal precursors. Long noncoding RNAs (lncRNAs) are commonly abnormal expressed in many cancers. In the present study, we fousced on one newly discrovered lncRNA, MYLK Antisense RNA 1 (MYLK‐AS1), and its functional role in proliferation and cycle distribution of nephroblastoma cells. Micorarray‐based analysis revealed the highly expressed Cyclin E1 (CCNE1) and MYLK‐AS1 in nephroblastoma. After nephroblastoma tissue sample collection, RT‐qPCR confirmed the upregulated expression of MYLK‐AS1 and CCNE1 in nephroblastoma tissues and cells. Kaplan–Meier curve exhibited that patients with elevated CCNE1 had lower overall survival rate in follow‐up study. RNA binding protein immunoprecipitation, chromatin immunoprecipitation, and dual‐luciferase reporter gene assay were employed to determine the relationship among MYLK‐AS1, TCF7L2, and CCNE1, which validated that transcription factor 7‐like 2 (TCF7L2) could specifically bind to MYLK‐AS1 and TCF7L2 could positively promote CCNE1. After gain‐ and loss‐of function assays, the conclusion that silencing of MYLK‐AS1 could inhibit expression of CCNE1 through the transcription factor TCF7L2 to regulate the cell proliferation and cell cycle distribution of nephroblastoma cells was obtained. Subsequently, the subcutaneous tumor formation ability of nephroblastoma cell in nude mice was observed and the silencing of MYLK‐AS1 exerts suppressive role in the tumorigenic ability of nephroblastoma cells in vivo. Taken together, MYLK‐AS1 constitutes a promising biomarker for the early detection and treatment of nephroblastoma.
Vitamin C deficient reduces proliferation in a human periventricular tumor stem cell‐derived glioblastoma model
Authors: Jara Nery , Ramirez Eder , Ferrada Luciano , Salazar Katterine , Espinoza Francisca , González‐Chavarría Iván , Nualart Francisco
Published: January 2021

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a median survival of 14.6 months. GBM is highly resistant to radio‐ and chemotherapy, and remains without a cure; hence, new treatment strategies are constantly sought. Vitamin C, an essential micronutrient and antioxidant, was initially described as an antitumor molecule; however, several studies have shown that it can promote tumor progression and angiogenesis. Thus, considering the high concentrations of vitamin C present in the brain, our aim was to study the effect of vitamin C deficiency on the progression of GBM using a GBM model generated by the stereotactic injection of human GBM cells (U87‐MG or HSVT‐C3 cells) in the subventricular zone of guinea pig brain. Initial characterization of U87‐MG and HSVT‐C3 cells showed that HSVT‐C3 are highly proliferative, overexpress p53, and are resistant to ferroptosis. To induce intraperiventricular tumors, animals received control or a vitamin C‐deficient diet for 3 weeks, after which histopathological and confocal microscopy analyses were performed. We demonstrated that the vitamin C‐deficient condition reduced the glomeruloid vasculature and microglia/macrophage infiltration in U87‐MG tumors. Furthermore, tumor size, proliferation, glomeruloid vasculature, microglia/macrophage infiltration, and invasion were reduced in C3 tumors carried by vitamin C‐deficient guinea pigs. In conclusion, the effect of the vitamin C deficiency was dependent on the tumor cell used for GBM induction. HSVT‐C3 cells, a cell line with stem cell features isolated from a human subventricular GBM, showed higher sensitivity to the deficient condition; however, vitamin C deficiency displayed an antitumor effect in both GBM models analyzed.
BKCa channel participates in insulin‐induced lipid deposition in adipocytes by increasing intracellular calcium
Authors: Ren Jie , Cheng Yuan , Wen Xinxin , Liu Ping , Zhao Feng , Xin Fang , Wang Meili , Huang Haixia , Wang Wei
Published: January 2021

Storing energy in the form of triglyceride (TG) is one of the basic functions of adipose tissue. Large‐conductance calcium‐activated potassium channels (BKCa channels) are expressed in adipose tissue and adipocyte‐specific BKCa deficiency resists obesity in mice, but the role of BKCa channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BKCa knockout (KO) rats and performed a transcriptome analysis of adipose tissue. We found that the phosphoinositide 3‐kinase (PI3K)–protein kinase B (Akt) signaling pathway, which is important for lipid deposition, exhibited the most notable reduction among various signaling pathways in BKCa KO rats compared to wild‐type rats. Insulin‐induced TG deposition, glucose uptake, and Akt (Ser473) phosphorylation were significantly reduced in cultured adipocytes differentiated from adipose‐derived stem cells of BKCa KO rats. Furthermore, we found that the insulin‐induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BKCa KO adipocytes. Finally, insulin activated BKCa currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BKCa channels participate in the insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes.
An unusual case of painless type A aortic dissection
Authors: Sonaglioni Andrea , Lombardo Michele , Rigamonti Elisabetta , Nicolosi Gian Luigi , Trevisan Roberta , Zompatori Maurizio , Anzà Claudio
Published: January 2021

The pathogenesis of acute aortic dissection (AAD) is not fully elucidated yet, but it was recently shown that inflammation contributes to the occurrence and development of both Stanford type A and type B AAD. We describe a rare case of a painless type A aortic dissection that occurred in an 85‐year‐old male, with moderate calcified aortic stenosis and a moderately dilated ascending aorta in 6‐month clinical and echocardiographic follow‐up. A chronic calculous cholecystitis with neutrophilic leukocytosis and severely increased C reactive protein was diagnosed in the last 3 months. In this patient, a chronic systemic inflammatory state might have contributed to generate the intimal entry tear in the aortic root. In particular, a neutrophil mobilization might have played a causative role in aortic rupture.
Expansion of arbitrary stimulus classes and function‐transfer measured by sorting performances
Authors: Arntzen Erik , Dechsling Anders , Fields Lanny
Published: January 2021

Sorting (SRT) and matching‐to‐sample (MTS) tests have measured the formation of arbitrary stimulus classes. This experiment used SRT and MTS tests to document the expansion of class size. Thirty‐two participants learned 12 conditional discriminations with a linear series training structure (A➔B➔C➔D➔E). SRT tests documented the formation of 5‐member classes by 17 of the participants. Thereafter, 6‐member class expansion was implemented by FC training. Nine of these 17 participants showed class expansion when tracked with a sequence of an SRT, MTS, and a final SRT test, and the other 8 showed expansion when tracked with a sequence of MTS and SRT tests. Thus, SRT tests documented class expansion, and the sequence of tests did not influence class expansion. The 15 participants who did not form the 5‐member classes learned the baselines for new 3‐member classes (A➔B➔C) and formed them as documented by an SRT test. Then, 4‐member class expansion was implemented by FB training. Expansion was assessed using the above‐mentioned testing sequences. All 15 showed class expansion with 100% correspondence between the SRT and MTS performances. Sorting documented the expansion of arbitrary stimulus classes, while the MTS tests showed that the stimuli also functioned as members of equivalence classes.
Urea nitrate–catalyzed C‐N and C‐S bond formation: A mechanochemical approach for 5‐chloro‐2‐arylbenzo[d]thiazole derivatives
Authors: Sethiya Ayushi , Sahiba Nusrat , Soni Jay , Agarwal Shikha
Published: January 2021

A series of substituted 5‐chloro‐2‐arylbenzo[d]thiazoles were synthesized using 4‐chloro‐2‐aminothiophenol and aromatic aldehydes in the presence of urea nitrate as a catalyst using the mechanochemical grindstone technique. This protocol was effectively carried out under metal‐free conditions at room temperature, and the desired products were obtained in high to excellent yields in short reaction time (30–60 s). The structure of all the synthesized derivatives was confirmed by spectral characterization. The designed protocol has several benefits like eco‐friendly, solvent‐free, high yields, easy workup, and recyclability of catalyst. The catalyst was reusable at least four times without significant loss of activity. The good functional group tolerance with a series of derivatives has been demonstrated.
A highly reproducible method for the measurement of [6‐O‐methyl‐11C]diprenorphine and its radio‐metabolites based on solid‐phase extraction and radio‐high‐pressure liquid chromatography
Authors: Fairclough Michael , McMahon Adam , Barnett Elizabeth , Matthews Julian , Brown Christopher A. , Jones Anthony
Published: January 2021

Described here is a method for the measurement of the radio‐metabolites of the positron emission tomography radiotracer [6‐O‐methyl‐11C]diprenorphine ([11C]diprenorphine) using in‐line solid‐phase extraction (SPE) combined with radio‐high‐pressure liquid chromatography analysis. We believe that this method offers a reliable and reproducible approach to [11C]diprenorphine metabolite analysis. In addition, different SPE stationary phases are assessed for their efficiency for loading, retention and elution of the parent molecule and its metabolites. Having assessed C4, phenyl and C18 stationary phase, we concluded that a C18 SPE was optimal for our method. Finally, in silico predictions of diprenorphine metabolism were compared with in vivo metabolism of [11C]diprenorphine induced by hepatic microsomal digestion and analysed by matrix‐assisted laser desorption/ionisation mass spectrometry. It was found that there was a high degree of agreement between the two methods and in particular the formation of the diprenorphine‐3‐glucuronide metabolite.
Noninvasive oxygenation assessment after acute myocardial infarction with breathing maneuvers‐induced oxygenation‐sensitive magnetic resonance imaging
Authors: Shi Ke , Yang Meng‐Xi , Xia Chun‐Chao , Peng Wan‐Lin , Zhang Kun , Li Zhen‐Lin , Guo Ying‐Kun , Yang Zhi‐Gang
Published: January 2021

The safety profiles when performing stress oxygenation‐sensitive magnetic resonance imaging (OS‐MRI) have raised concerns in clinical practice. Adenosine infusion can cause side effects such as chest pain, dyspnea, arrhythmia, and even cardiac death. The aim of this study was to investigate the feasibility of breathing maneuvers‐induced OS‐MRI in acute myocardial infarction (MI). This was a prospective study, which included 14 healthy rabbits and nine MI rabbit models. This study used 3 T MRI/modified Look‐Locker inversion recovery sequence for native T1 mapping, balanced steady‐state free precession sequence for OS imaging, and phase‐sensitive inversion recovery sequence for late gadolinium enhancement. The changes in myocardial oxygenation (ΔSI) were assessed under two breathing maneuvers protocols in healthy rabbits: a series of extended breath‐holding (BH), and a combined maneuver of hyperventilation followed by the extended BH (HVBH). Subsequently, OS‐MRI with HVBH in acute MI rabbits was performed, and the ΔSI was compared with that of adenosine stress protocol. Student's t‐test, Wilcoxon rank test, and Friedman test were used to compare ΔSI in different subgroups. Pearson and Spearman correlation was used to obtain the association of ΔSI between breathing maneuvers and adenosine stress. Bland–Altman analysis was used to assess the bias of ΔSI between HVBH and adenosine stress. In healthy rabbits, BH maneuvers from 30 to 50 s induced significant increase in SI compared with the baseline (all p < 0.05). By contrast, hyperventilation for 60 s followed by 10 s‐BH (HVBH 10 s) exhibited a comparable ΔSI to that of stress test (p = 0.07). In acute MI rabbits, HVBH 10 s‐induced ΔSIs among infarcted, salvaged, and the remote myocardial area were no less effectiveness than adenosine stress when performing OS‐MRI (r = 0.84; p < 0.05). Combined breathing maneuvers with OS‐MRI have the potential to be used as a nonpharmacological alternative for assessing myocardial oxygenation in patients with acute MI.

Level of Evidence

2

Technical Efficacy Stage

2
SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells
Authors: Li Na , Li Jiajia , Desiderio Dominic M. , Zhan Xianquan
Published: January 2021

The antiparasitic agent ivermectin offers more promises to treat a diverse range of diseases. However, a comprehensive proteomic analysis of ivermectin‐treated ovarian cancer (OC) cells has not been performed. This study sought to identify ivermectin‐related proteomic profiling and molecular network alterations in human OC cells. Stable isotope labeling with amino acids in cell culture (SILAC)‐based quantitative proteomics was used to study the human OC TOV‐21G cells. After TOV‐21G cells underwent 10 passages in SILAC‐labeled growth media, TOV‐21G cells were treated with 10 ml of 20 μmol/L ivermectin in cell growing medium for 24 h. The SILAC‐labeled proteins were digested with trypsin; tryptic peptides were identified with mass spectrometry (MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to mine signaling pathway alterations with ivermectin‐related proteins in TOV‐21G cells. Gene ontology (GO) analysis was used to explore biological functions of ivermectin‐related proteins, including biological processes (BPs), cellular components (CCs), and molecular functions (MFs). The protein‐protein interaction network was analyzed with molecular complex detection (MCODE) to identify hub modules. In total, 4,447 proteins were identified in ivermectin‐treated TOV‐21G cells. KEGG analysis revealed 89 statistically significant signaling pathways. Interestingly, the clustering analysis of these pathways showed that ivermectin was involved in various cancer pathogenesis processes, including modulation of replication, RNA metabolism, and translational machinery. GO analysis revealed 69 statistically significant CCs, 87 MFs, and 62 BPs. Furthermore, MCODE analysis identified five hub modules, including 147 hub molecules. Those hub modules involved ribosomal proteins, RNA‐binding proteins, cell‐cycle progression‐related proteins, proteasome subunits, and minichromosome maintenance proteins. These findings demonstrate that SILAC quantitative proteomics is an effective method to analyze ivermectin‐treated cells, provide the first ivermectin‐related proteomic profiling and molecular network alterations in human OC cells, and provide deeper insights into molecular mechanisms and functions of ivermectin to inhibit OC cells.
Top–down lignomics analysis of the French oak lignin by atmospheric pressure photoionization and electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry: Identification of a novel series of lignans
Authors: Mikhael Abanoub , Fridgen Travis D. , Delmas Michel , Banoub Joseph
Published: January 2021

We report herein the top–down lignomic analysis of virgin released lignin (VRL) extracted from the French oak wood using atmospheric pressure photoionization quadrupole orthogonal time‐of‐flight mass spectrometry (APPI‐QqTOF‐MS) (+ ion mode). Eight major protonated lignin oligomers were identified using the APPI‐QqTOF‐MS/MS of this complex VRL mixture without any kind of purification. This series of protonated oligomer ions were identified as neolignan cedrusin (1), five different aryltetralin lignans dimers (2–6), one lignan‐dehydroshikimic acid complex (7), and a lignan trimer (8). Similarly, electrospray ionization (ESI)‐QqTOF‐MS (+ ion mode) allowed us to identify three extra aryltetralin lignan derivatives (9–11). The Kendrick mass defect analysis was used for the simplification of this complex APPI‐QqTOF‐MS into a compositional map, which displayed clustering points of associated ions possessing analogous elemental composition. This series of novel protonated molecules were selected and subjected to low‐energy collision‐induced dissociation (CID)‐MS/MS analyses. The obtained gas‐phase fragmentation patterns helped to tentatively assign their most likely structures. Also, it was found that the use of different APPI and ESI ambient ionization techniques enhances the ionization of different types of lignin oligomers.