bluuebunny/crossref_metadata_2025 huggingface dataset:
Growing Human Hepatocellular Tumors Undergo a Global Metabolic Reprogramming
Authors: Zhang Fangrong , Wang Yingchao , Chen Geng , Li Zhenli , Xing Xiaohua , Putz-Bankuti Csilla , Stauber Rudolf E. , Liu Xiaolong , Madl Tobias
Published: April 2021

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis, high morbidity and mortality concerning with lack of effective diagnosis and high postoperative recurrence. Similar with other cancers, HCC cancer cells have to alter their metabolism to adapt to the changing requirements imposed by the environment of the growing tumor. In less vascularized regions of tumor, cancer cells experience hypoxia and nutrient starvation. Here, we show that HCC undergoes a global metabolic reprogramming during tumor growth. A combined proteomics and metabolomics analysis of paired peritumoral and tumor tissues from 200 HCC patients revealed liver-specific metabolic reprogramming and metabolic alterations with increasing tumor sizes. Several proteins and metabolites associated with glycolysis, the tricarboxylic acid cycle and pyrimidine synthesis were found to be differentially regulated in serum, tumor and peritumoral tissue with increased tumor sizes. Several prognostic metabolite biomarkers involved in HCC metabolic reprogramming were identified and integrated with clinical and pathological data. We built and validated this combined model to discriminate against patients with different recurrence risks. An integrated and comprehensive metabolomic analysis of HCC is provided by our present work. Metabolomic alterations associated with the advanced stage of the disease and poor clinical outcomes, were revealed. Targeting cancer metabolism may deliver effective therapies for HCC.
Fibroblast MMP14-Dependent Collagen Processing Is Necessary for Melanoma Growth
Authors: Pach Elke , Brinckmann Jürgen , Rübsam Matthias , Kümper Maike , Mauch Cornelia , Zigrino Paola
Published: April 2021

Skin homeostasis results from balanced synthesis and degradation of the extracellular matrix in the dermis. Deletion of the proteolytic enzyme MMP14 in dermal fibroblasts (MMP14Sf−/−) leads to a fibrotic skin phenotype with the accumulation of collagen type I, resulting from impaired proteolysis. Here, we show that melanoma growth in these mouse fibrotic dermal samples was decreased, paralleled by reduced tumor cell proliferation and vessel density. Using atomic force microscopy, we found increased peritumoral matrix stiffness of early but not late melanomas in the absence of fibroblast-derived MMP14. However, total collagen levels were increased at late melanoma stages in MMP14Sf−/− mice compared to controls. In ex vivo invasion assays, melanoma cells formed smaller tumor islands in MMP14Sf−/− skin, indicating that MMP14-dependent matrix accumulation regulates tumor growth. In line with these data, in vitro melanoma cell growth was inhibited in high collagen 3D spheroids or stiff substrates. Most importantly, in vivo induction of fibrosis using bleomycin reduced melanoma tumor growth. In summary, we show that MMP14 expression in stromal fibroblasts regulates melanoma tumor progression by modifying the peritumoral matrix and point to collagen accumulation as a negative regulator of melanoma.
One-Step Preparation of Biochar Electrodes and Their Applications in Sediment Microbial Electrochemical Systems
Authors: You Kui , Zhou Zihan , Gao Chao , Yang Qiao
Published: April 2021

Biochar is a kind of carbon-rich material formed by pyrolysis of biomass at high temperature in the absence or limitation of oxygen. It has abundant pore structure and a large surface area, which could be considered the beneficial characteristics for electrodes of microbial electrochemical systems. In this study, reed was used as the raw material of biochar and six biochar-based electrode materials were obtained by three methods, including one-step biochar cathodes (BC 800 and BC 700), biochar/polyethylene composite cathodes (BP 5:5 and BP 6:4), and biochar/polyaniline/hot-melt adhesive composite cathode (BPP 5:1:4 and BPP 4:1:5). The basic physical properties and electrochemical properties of the self-made biochar electrode materials were characterized. Selected biochar-based electrode materials were used as the cathode of sediment microbial electrochemical reactors. The reactor with pure biochar electrode (BC 800) achieves a maximum output power density of 9.15 ± 0.02 mW/m2, which increases the output power by nearly 80% compared with carbon felt. When using a biochar/polyaniline/hot-melt adhesive (BPP 5:1:4) composite cathode, the output power was increased by 2.33 times. Under the premise of ensuring the molding of the material, the higher the content of biochar, the better the electrochemical performance of the electrodes. The treatment of reed powder before pyrolysis is an important factor for the molding of biochar. The one-step molding biochar cathode had satisfactory performance in sediment microbial electrochemical systems. By exploring the biochar-based electrode, waste biomass could be reused, which is beneficial for the environment.
Non-Thermal Plasma-Assisted Catalytic Reactions for Environmental Protection
Authors: Vaiano Vincenzo , Iervolino Giuseppina
Published: April 2021

“Non-thermal plasma technology” (NTP) has notably increased [...]
Palladium Particles Modified by Mixed-Frequency Square-Wave Potential Treatment to Enhance Electrocatalytic Performance for Formic Acid Oxidation
Authors: Li Fangchao , Liu Bin , Shen Yuanhao , Liu Jie , Zhong Cheng , Hu Wenbin
Published: April 2021

Palladium catalysts have attracted widespread attention as advanced electrocatalysts for the formic acid oxidation (FAO) due to their excellent electrocatalytic activity and relatively high abundance. At present, electrodeposition methods have been widely developed to prepare small-sized and highly-dispersed Pd electrocatalysts. However, the customary use of surfactants would introduce heterogeneous impurities, which requires complicated removal processes. In this work, we reported a two-step electrochemical method that employed square-wave potential treatment (SWPT) to modify electrodeposited Pd particles without the use of capping agents. Under the SWPT with a mixed frequency, Pd particles show significantly reduced size and more dispersed distribution, exhibiting a high mass activity of 1.43 A mg−1 toward FAO, which is 4.6 times higher than the counterpart of commercial Pd/C. The increase in electrocatalytic activity of FAO is attributed to the highly developed surface of palladium particles uniformly distributed over the support surface.
The Effect of the Clenbuterol—β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro
Authors: Witkowska-Piłaszewicz Olga , Pingwara Rafał , Szczepaniak Jarosław , Winnicka Anna
Published: April 2021

Clenbuterol, the β2-adrenoceptor agonist, is gaining growing popularity because of its effects on weight loss (i.e., chemical liposuction). It is also popular in bodybuilding and professional sports, due to its effects that are similar to anabolic steroids. However, it is prohibited by anti-doping control. On the other hand, it is suggested that clenbuterol can inhibit the inflammatory process. The cells from 14 untrained and 14 well-trained race horses were collected after acute exercise and cultured with clenbuterol. The expressions of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ and TNF-α concentrations were evaluated by ELISA. β2-adrenoceptor stimulation leads to enhanced anti-inflammatory properties in well-trained horses, as do low doses in untrained animals. In contrast, higher clenbuterol doses create a pro-inflammatory environment in inexperienced horses. In conclusion, β2-adrenoceptor stimulation leads to a biphasic response. In addition, the immune cells are more sensitive to drug abuse in inexperienced individuals under physical training.
The Expression Regulation and Biological Function of Autotaxin
Authors: Zhang Xiaotian , Li Mengmiao , Yin Nan , Zhang Junjie
Published: April 2021

Autotaxin (ATX) is a secreted glycoprotein and functions as a key enzyme to produce extracellular lysophosphatidic acid (LPA). LPA interacts with at least six G protein-coupled receptors, LPAR1-6, on the cell membrane to activate various signal transduction pathways through distinct G proteins, such as Gi/0, G12/13, Gq/11, and Gs. The ATX-LPA axis plays an important role in physiological and pathological processes, including embryogenesis, obesity, and inflammation. ATX is one of the top 40 most unregulated genes in metastatic cancer, and the ATX-LPA axis is involved in the development of different types of cancers, such as colorectal cancer, ovarian cancer, breast cancer, and glioblastoma. ATX expression is under multifaceted controls at the transcription, post-transcription, and secretion levels. ATX and LPA in the tumor microenvironment not only promote cell proliferation, migration, and survival, but also increase the expression of inflammation-related circuits, which results in poor outcomes for patients with cancer. Currently, ATX is regarded as a potential cancer therapeutic target, and an increasing number of ATX inhibitors have been developed. In this review, we focus on the mechanism of ATX expression regulation and the functions of ATX in cancer development.
Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury
Authors: Hong Jung Yeon , Kim Mi Na , Kim Eun Gyul , Lee Jae Woo , Kim Hye Rin , Kim Soo Yeon , Lee Soon Min , Kim Yoon Hee , Kim Kyung Won , Sohn Myung Hyun
Published: April 2021

Exposure to high oxygen concentrations leads to generation of excessive reactive oxygen species, causing cellular injury and multiple organ dysfunctions and is associated with a high mortality rate. Clusterin (CLU) is a heterodimeric glycoprotein that mediates several intracellular signaling pathways, including cell death and inflammation. However, the role of CLU in the pathogenesis of hyperoxic acute lung injury (HALI) is unknown. Wild-type (WT) and CLU-deficient mice and cultured human airway epithelial cells were used. Changes in cell death- and inflammation-related molecules with or without hyperoxia exposure in cells and animals were determined. Hyperoxia induced an increase in CLU expression in mouse lungs and human airway epithelial cells. Mice lacking CLU had increased HALI and mortality rate compared with WT mice. In vitro, CLU-disrupted cells showed enhanced release of cytochrome c, Bax translocation, cell death and inflammatory cytokine expression. However, treatment with recombinant CLU attenuated hyperoxia-induced apoptosis. Moreover, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed metabolic pathways, hematopoietic cell lineage, response to stress and localization and regulation of immune system that were differentially regulated between WT and CLU−/− mice. These results demonstrate that prolonged hyperoxia-induced lung injury is associated with CLU expression and that CLU replenishment may alleviate hyperoxia-induced cell death.
Learning Yeast Genetics from Miro Radman
Authors: Haber James E.
Published: April 2021

Miroslav Radman’s far-sighted ideas have penetrated many aspects of our study of the repair of broken eukaryotic chromosomes. For over 35 years my lab has studied different aspects of the repair of chromosomal breaks in the budding yeast, Saccharomyces cerevisiae. From the start, we have made what we thought were novel observations that turned out to have been predicted by Miro’s extraordinary work in the bacterium Escherichia coli and then later in the radiation-resistant Dienococcus radiodurans. In some cases, we have been able to extend some of his ideas a bit further.
BKCa Channel Inhibition by Peripheral Nerve Injury Is Restored by the Xanthine Derivative KMUP-1 in Dorsal Root Ganglia
Authors: Cheng Kuang-I , Yang Kan-Ting , Kung Chien-Lun , Cheng Yu-Chi , Yeh Jwu-Lai , Dai Zen-Kong , Wu Bin-Nan
Published: April 2021

This study explored whether KMUP-1 improved chronic constriction injury (CCI)-induced BKCa current inhibition in dorsal root ganglion (DRG) neurons. Rats were randomly assigned to four groups: sham, sham + KMUP-1, CCI, and CCI + KMUP-1 (5 mg/kg/day, i.p.). DRG neuronal cells (L4–L6) were isolated on day 7 after CCI surgery. Perforated patch-clamp and inside-out recordings were used to monitor BKCa currents and channel activities, respectively, in the DRG neurons. Additionally, DRG neurons were immunostained with anti-NeuN, anti-NF200 and anti-BKCa. Real-time PCR was used to measure BKCa mRNA levels. In perforated patch-clamp recordings, CCI-mediated nerve injury inhibited BKCa currents in DRG neurons compared with the sham group, whereas KMUP-1 prevented this effect. CCI also decreased BKCa channel activity, which was recovered by KMUP-1 administration. Immunofluorescent staining further demonstrated that CCI reduced BKCa-channel proteins, and KMUP-1 reversed this. KMUP-1 also changed CCI-reduced BKCa mRNA levels. KMUP-1 prevented CCI-induced neuropathic pain and BKCa current inhibition in a peripheral nerve injury model, suggesting that KMUP-1 could be a potential agent for controlling neuropathic pain.
The Role of RhoH in TCR Signalling and Its Involvement in Diseases
Authors: Ahmad Mokhtar Ana Masara , Hashim Ilie Fadzilah , Mohd Zaini Makhtar Muaz , Salikin Nor Hawani , Amin-Nordin Syafinaz
Published: April 2021

As an atypical member of the Rho family small GTPases, RhoH shares less than 50% sequence similarity with other members, and its expression is commonly observed in the haematopoietic lineage. To date, RhoH function was observed in regulating T cell receptor signalling, and less is known in other haematopoietic cells. Its activation may not rely on the standard GDP/GTP cycling of small G proteins and is thought to be constitutively active because critical amino acids involved in GTP hydrolysis are absent. Alternatively, its activation can be regulated by other types of regulation, including lysosomal degradation, somatic mutation and transcriptional repressor, which also results in an altered protein expression. Aberrant protein expression of RhoH has been implicated not only in B cell malignancies but also in immune-related diseases, such as primary immunodeficiencies, systemic lupus erythematosus and psoriasis, wherein its involvement may provide the link between immune-related diseases and cancer. RhoH association with these diseases involves several other players, including its interacting partner, ZAP−70; activation regulators, Vav1 and RhoGDI and other small GTPases, such as RhoA, Rac1 and Cdc42. As such, RhoH and its associated proteins are potential attack points, especially in the treatment of cancer and immune-related diseases.
Paraburkholderia phymatum Homocitrate Synthase NifV Plays a Key Role for Nitrogenase Activity during Symbiosis with Papilionoids and in Free-Living Growth Conditions
Authors: Bellés-Sancho Paula , Lardi Martina , Liu Yilei , Hug Sebastian , Pinto-Carbó Marta Adriana , Zamboni Nicola , Pessi Gabriella
Published: April 2021

Homocitrate is an essential component of the iron-molybdenum cofactor of nitrogenase, the bacterial enzyme that catalyzes the reduction of dinitrogen (N2) to ammonia. In nitrogen-fixing and nodulating alpha-rhizobia, homocitrate is usually provided to bacteroids in root nodules by their plant host. In contrast, non-nodulating free-living diazotrophs encode the homocitrate synthase (NifV) and reduce N2 in nitrogen-limiting free-living conditions. Paraburkholderia phymatum STM815 is a beta-rhizobial strain, which can enter symbiosis with a broad range of legumes, including papilionoids and mimosoids. In contrast to most alpha-rhizobia, which lack nifV, P. phymatum harbors a copy of nifV on its symbiotic plasmid. We show here that P. phymatum nifV is essential for nitrogenase activity both in root nodules of papilionoid plants and in free-living growth conditions. Notably, nifV was dispensable in nodules of Mimosa pudica despite the fact that the gene was highly expressed during symbiosis with all tested papilionoid and mimosoid plants. A metabolome analysis of papilionoid and mimosoid root nodules infected with the P. phymatum wild-type strain revealed that among the approximately 400 measured metabolites, homocitrate and other metabolites involved in lysine biosynthesis and degradation have accumulated in all plant nodules compared to uninfected roots, suggesting an important role of these metabolites during symbiosis.
Proteome Damage Inflicted by Ionizing Radiation: Advancing a Theme in the Research of Miroslav Radman
Authors: Bruckbauer Steven T. , Minkoff Benjamin B. , Sussman Michael R. , Cox Michael M.
Published: April 2021

Oxidative proteome damage has been implicated as a major contributor to cell death and aging. Protein damage and aging has been a particular theme of the recent research of Miroslav Radman. However, the study of how cellular proteins are damaged by oxidative processes is still in its infancy. Here we examine oxidative changes in the proteomes of four bacterial populations—wild type E. coli, two isolates from E. coli populations evolved for high levels of ionizing radiation (IR) resistance, and D. radiodurans—immediately following exposure to 3000 Gy of ionizing radiation. By a substantial margin, the most prominent intracellular oxidation events involve hydroxylation of methionine residues. Significant but much less frequent are carbonylation events on tyrosine and dioxidation events on tryptophan. A few proteins are exquisitely sensitive to targeted oxidation events, notably the active site of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in E. coli. Extensive experimental evolution of E. coli for IR resistance has decreased overall proteome sensitivity to oxidation but not to the level seen in D. radiodurans. Many observed oxidation events may reflect aspects of protein structure and/or exposure of protein surfaces to water. Proteins such as GAPDH and possibly Ef-Tu may have an evolved sensitivity to oxidation by H2O2.
Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease
Authors: Casali Brad T. , Reed-Geaghan Erin G.
Published: April 2021

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.
Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases
Authors: Yamashita Toru , Kushida Yoshihiro , Abe Koji , Dezawa Mari
Published: April 2021

Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant. They express receptors for sphingosine-1-phosphate (S1P), which is actively produced by damaged cells, allowing circulating cells to selectively home to damaged tissue. Muse cells spontaneously differentiate on-site into multiple tissue-constituent cells with few errors and replace damaged/apoptotic cells with functional cells, thereby contributing to tissue repair. Intravenous injection of exogenous Muse cells to increase the number of circulating Muse cells enhances their reparative activity. Muse cells also have a specific immunomodulatory system, represented by HLA-G expression, allowing them to be directly administered without HLA-matching or immunosuppressant treatment. Owing to these unique characteristics, clinical trials using intravenously administered donor-Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, and amyotrophic lateral sclerosis. Muse cells have the potential to break through the limitations of current cell therapies for neurologic diseases, including amyotrophic lateral sclerosis. Muse cells provide a new therapeutic strategy that requires no HLA-matching or immunosuppressant treatment for administering donor-derived cells, no gene introduction or differentiation induction for cell preparation, and no surgery for delivering the cells to patients.
Transcryptomic Analysis of Human Brain-Microvascular Endothelial Response to -Pericytes: Cell Orientation Defines Barrier Function
Authors: Kurmann Lisa , Okoniewski Michal , Ogunshola Omolara O. , Leeners Brigitte , Imthurn Bruno , Dubey Raghvendra K.
Published: April 2021

Pericytes facilitate blood–brain barrier (BBB) integrity; however, the mechanisms involved remain unclear. Hence, using co-cultures of human cerebral microvascular endothelial cells (ECs) and vascular pericytes (PCs) in different spatial arrangements, as well as PC conditioned media, we investigated the impact of PC-EC orientation and PC-derived soluble factors on EC barrier function. We provide the first evidence that barrier-inducing properties of PCs require basolateral contact with ECs. Gene expression analysis (GEA) in ECs co-cultured with PCs versus ECs alone showed significant upregulation of 38 genes and downregulation of 122 genes. Pathway enrichment analysis of modulated genes showed significant regulation of several pathways, including transforming growth factor-β and interleukin-1 regulated extracellular matrix, interferon and interleukin signaling, immune system signaling, receptor of advanced glycation end products (RAGE), and cytokine–cytokine receptor interaction. Transcriptomic analysis showed a reduction in molecules such as pro-inflammatory cytokines and chemokines, which are known to be induced during BBB disruption. Moreover, cytokine proteome array confirmed the downregulation of key pro-inflammatory cytokines and chemokines on the protein level. Other molecules which influence BBB and were favorably modulated upon EC-PC co-culture include IL-18 binding protein, kallikrein-3, CSF2 CSF3, CXCL10, CXCL11 (downregulated) and IL-1-R4; HGF, PDGF-AB/BB, PECAM, SERPIN E1 (upregulated). In conclusion, we provide the first evidence that (1) basolateral contact between ECs and PCs is essential for EC barrier function and integrity; (2) in ECs co-cultured with PCs, the profile of BBB disrupting pro-inflammatory molecules and cytokines/chemokines is downregulated; (3) PCs significantly modulate EC mechanisms known to improve barrier function, including TGF-β regulated ECM pathway, anti-inflammatory cytokines, growth factors and matrix proteins. This human PC-EC co-culture may serve as a viable in vitro model for investigating BBB function and drug transport.
Venous Malformations and Blood Coagulation in Children
Authors: Aronniemi Johanna , Långström Satu , Mattila Katariina A. , Mäkipernaa Anne , Salminen Päivi , Pitkäranta Anne , Pekkola Johanna , Lassila Riitta
Published: April 2021

Introduction: Venous malformations (VMs) are congenital low-flow lesions with a wide spectrum of clinical manifestations. An increasing number of studies link VMs to coagulation abnormalities, especially to elevated D-dimer and decreased fibrinogen. This condition, termed localized intravascular coagulopathy (LIC), may pose a risk for hemostatic complications. However, detailed data on the laboratory variables for coagulation and fibrinolytic activity in VM patients are limited. We addressed this question by systematically analyzing the coagulation parameters in pediatric VM patients. Methods: We included 62 patients (median age 11.9 years) with detailed laboratory tests for coagulation and fibrinolytic activity at a clinically steady phase. We assessed clinical and imaging features of VMs and their correlations with coagulation and fibrinolysis variables using patient records and MRI. Results: D-dimer was elevated in 39% and FXIII decreased in 20% of the patients, as a sign of LIC. Elevated D-dimer and decreased FXIII were associated with large size, deep location, and diffuse and multifocal VMs. FVIII was elevated in 17% of the patients and was associated with small VM size, superficial and confined location, discrete morphology, and less pain. Surprisingly, antithrombin was elevated in 55% of the patients but without associations with clinical or other laboratory variables. Conclusions: LIC was common in pediatric patients with VMs. Our results provide a basis for when evaluating the risks of hemostatic complications in children with VMs. Further research is warranted to explore the mechanisms behind coagulation disturbances and their relation to clinical complications.
XGRN: Reconstruction of Biological Networks Based on Boosted Trees Regression
Authors: Dimitrakopoulos Georgios N.
Published: April 2021

In Systems Biology, the complex relationships between different entities in the cells are modeled and analyzed using networks. Towards this aim, a rich variety of gene regulatory network (GRN) inference algorithms has been developed in recent years. However, most algorithms rely solely on gene expression data to reconstruct the network. Due to possible expression profile similarity, predictions can contain connections between biologically unrelated genes. Therefore, previously known biological information should also be considered by computational methods to obtain more consistent results, such as experimentally validated interactions between transcription factors and target genes. In this work, we propose XGBoost for gene regulatory networks (XGRN), a supervised algorithm, which combines gene expression data with previously known interactions for GRN inference. The key idea of our method is to train a regression model for each known interaction of the network and then utilize this model to predict new interactions. The regression is performed by XGBoost, a state-of-the-art algorithm using an ensemble of decision trees. In detail, XGRN learns a regression model based on gene expression of the two interactors and then provides predictions using as input the gene expression of other candidate interactors. Application on benchmark datasets and a real large single-cell RNA-Seq experiment resulted in high performance compared to other unsupervised and supervised methods, demonstrating the ability of XGRN to provide reliable predictions.
High Thermal Stability of κ-Ga2O3 Grown by MOCVD
Authors: Lee Junhee , Kim Honghyuk , Gautam Lakshay , Razeghi Manijeh
Published: April 2021

We report a high thermal stability of kappa gallium oxide grown on c-plane sapphire substrate by metal organic chemical vapor deposition. Kappa gallium oxide is widely known as a metastable polymorph transitioning its phase when subjected to a high temperature. Here, we show the kappa gallium oxide whose phase is stable in a high temperature annealing process at 1000 °C. These oxide films were grown at 690 °C under nitrogen carrier gas. The materials showed high electrical resistivity when doped with silicon, whereas the film conductivity was significantly improved when doped with both indium and silicon. This work provides a pathway to overcoming limitations for the advance in utilizing kappa gallium oxide possessing superior electrical characteristics.
New Insight on Liquid Steel Microalloying by Pulse-Step Method in Two-Strand Slab Tundish by Numerical Simulations
Authors: Cwudziński Adam
Published: April 2021

Developing a technology for introducing alloy addition to liquid steel during the course of continuous casting process seems to be an interesting approach to enhancing the steelmaking process, especially as the effective introduction of micro-additives or non-metallic inclusion modifiers to the liquid steel is the key to the production of the highest-quality steel. This paper presents the results of investigation describing the process of liquid steel chemical homogenisation in the two-strand slab tundish. The alloy was fed to liquid steel by pulse-step method. Five tundish equipment variants with different flow control devices and alloy addition feeding positions were considered. The paper includes fields of liquid steel flow, alloy concentration vs. time curves, dimensionless mixing time, minimum time values and alloy concentration deviations at tundish outlets. The results pointed much more effectively with liquid steel mixing nickel than aluminium. For aluminium obtaining a 95% chemical homogenisation level requires three-fold more time. Moreover, it is definitely beneficial for chemical homogenisation to initiate the alloying process simultaneously in two sites. This procedure generates, among others, the least alloy deviation of concentration at tundish outlets.
Understanding the Reaction Crystallization Process of Glycidyl Trimethyl Ammonium Chloride
Authors: Yu Shuai , Chen Hui , Gao Xujie , Feng Weichun , Xing Wenguo , Du Shichao , Wang Yan , Xue Fumin , Cheng Yan
Published: April 2021

Reaction crystallization to produce glycidyl trimethyl ammonium chloride (GTA) via epichlorohydrin with gas-state trimethylamine was investigated. The crystallization process of the GTA gas-liquid reaction was optimized by a seed method. The optimized technology can prepare GTA products with crystal form and purity greater than 97%. The crystallization process of GTA consists of four steps (i.e., addition of seed, dispersion of seed, growth of crystals on the seed surfaces, agglomeration and growth of crystal). Seed method and flow rate are the key factors affecting purity. The purity and particle size of GTA crystals were satisfactory as long as the operation was kept within the defined envelope. The experiments were conducted on a 1 L reactor and successfully scaled-up to 3000 L in industry.
Strain Accommodations among Twin Variants in Ti and Mg
Authors: Zhou Ping , Zhu Guo-Zhen
Published: April 2021

The selection of twin variants has a great influence on deformation texture and mechanical property in hcp metals where slip systems are limited and twinning types are abundant during deformation. Local strain accommodations among twin variants are considered to shed light on variant selection rules in Ti and Mg alloys. Five kinds of strain accommodations are discussed in terms of different regions that are affected by the twinning shear of primary twin. These regions contain (I) the whole sample, (II) neighboring grain, (III) adjacent primary twin in neighboring grain, (IV) adjoining primary twin within the same parent grain, and (V) multi-generation of twinning inside the primary twin. For a potentially active variant, its operation needs not only relatively higher resolved shear stress but also easily accommodated strain by immediate vicinity. Many of the non-Schmid behaviors could be elucidated by local strain accommodations that variants with relatively higher SFs hard to be accommodated are absent, while those with relatively lower SFs but could be easily accommodated are present.
Comparative Hybrid Hartree-Fock-DFT Calculations of WO2-Terminated Cubic WO3 as Well as SrTiO3, BaTiO3, PbTiO3 and CaTiO3 (001) Surfaces
Authors: Eglitis R. I. , Purans Juris , Jia Ran
Published: April 2021

We performed, to the best of our knowledge, the world’s first first-principles calculations for the WO2-terminated cubic WO3 (001) surface and analyzed the systematic trends in the WO3, SrTiO3, BaTiO3, PbTiO3 and CaTiO3 (001) surface ab initio calculations. According to our first principles calculations, all WO2 or TiO2-terminated WO3, SrTiO3, BaTiO3, PbTiO3 and CaZrO3 (001) surface upper-layer atoms relax inwards towards the crystal bulk, while all second-layer atoms relax upwards. The only two exceptions are outward relaxations of first layer WO2 and TiO2-terminated WO3 and PbTiO3 (001) surface O atoms. The WO2 or TiO2-terminated WO3, SrTiO3, BaTiO3, PbTiO3 and CaTiO3 (001) surface-band gaps at the Γ–Γ point are smaller than their respective bulk-band gaps. The Ti–O chemical bond populations in the SrTiO3, BaTiO3, PbTiO3 and CaTiO3 bulk are smaller than those near the TiO2-terminated (001) surfaces. Conversely, the W–O chemical bond population in the WO3 bulk is larger than near the WO2-terminated WO3 (001) surface.
Associations between Pre-Bariatric High-Sensitivity C-Reactive Protein and Post-Surgery Outcomes
Authors: Jamialahmadi Tannaz , Nematy Mohsen , Bo Simona , Ponzo Valentina , Jangjoo Ali , Goshayeshi Ladan , Tasbandi Aida , Nikiforov Nikita , Sahebkar Amirhossein
Published: April 2021

Background: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) values and post-surgery weight loss and liver steatosis and fibrosis in patients with severe obesity undergoing Roux-en-Y gastric bypass. Methods: We conducted an observational prospective study on 90 individuals with morbid obesity, who underwent gastric bypass. Anthropometric indices, laboratory assessment (lipid panel, glycemic status, liver enzymes, and hs-CRP), liver stiffness and steatosis were evaluated at baseline and 6-months after surgery. Results: There was a significant post-surgery reduction in all the anthropometric variables, with an average weight loss of 33.93 ± 11.79 kg; the mean percentage of total weight loss (TWL) was 27.96 ± 6.43%. Liver elasticity was significantly reduced (from 6.1 ± 1.25 to 5.42 ± 1.52 kPa; p = 0.002), as well as liver aminotransferases, nonalcoholic fatty liver disease fibrosis score (NFS) and the grade of steatosis. Serum hs-CRP levels significantly reduced (from 9.26 ± 8.45 to 3.29 ± 4.41 mg/L; p < 0.001). The correlations between hs-CRP levels and liver fibrosis (elastography), steatosis (ultrasonography), fibrosis-4 index, NFS, and surgery success rate were not significant. Regression analyses showed that serum hs-CRP levels were not predictive of liver status and success rate after surgery in both unadjusted and adjusted models. Conclusions: In patients with morbid obesity, bariatric surgery caused a significant decrease in hs-CRP levels, liver stiffness and steatosis. Baseline hs-CRP values did not predict the weight-loss success rate and post-surgery liver status.
Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature
Authors: Oprean Cristina Marinela , Badau Larisa Maria , Segarceanu Nusa Alina , Ciocoiu Andrei Dorin , Rivis Ioana Alexandra , Vornicu Vlad Norin , Hoinoiu Teodora , Grujic Daciana , Bredicean Cristina , Dema Alis
Published: April 2021

The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.
Imbalance of Mg Homeostasis as a Potential Biomarker in Colon Cancer
Authors: Schiroli Davide , Marraccini Chiara , Zanetti Eleonora , Ragazzi Moira , Gianoncelli Alessandra , Quartieri Eleonora , Gasparini Elisa , Iotti Stefano , Baricchi Roberto , Merolle Lucia
Published: April 2021

Background: Increasing evidences support a correlation between magnesium (Mg) homeostasis and colorectal cancer (CRC). Nevertheless, the role of Mg and its transporters as diagnostic markers in CRC is still a matter of debate. In this study we combined X-ray Fluorescence Microscopy and databases information to investigate the possible correlation between Mg imbalance and CRC. Methods: CRC tissue samples and their non-tumoural counterpart from four patients were collected and analysed for total Mg level and distribution by X-Ray Fluorescence Microscopy. We also reviewed the scientific literature and the main tissue expression databases to collect data on Mg transporters expression in CRC. Results: We found a significantly higher content of total Mg in CRC samples when compared to non-tumoural tissues. Mg distribution was also impaired in CRC. Conversely, we evidenced an uncertain correlation between Mg transporters expression and colon malignancies. Discussion: Although further studies are necessary to determine the correlation between different cancer types and stages, this is the first report proposing the measurement of Mg tissue localisation as a marker in CRC. This study represents thus a proof-of-concept that paves the way for the design of a larger prospective investigation of Mg in CRC.
miRNAs and Their Gene Targets—A Clue to Differentiate Pregnancies with Small for Gestational Age Newborns, Intrauterine Growth Restriction, and Preeclampsia
Authors: Timofeeva Angelika V. , Fedorov Ivan S. , Brzhozovskiy Alexander G. , Bugrova Anna E. , Chagovets Vitaliy V. , Volochaeva Maria V. , Starodubtseva Natalia L. , Frankevich Vladimir E. , Nikolaev Evgeny N. , Shmakov Roman G. , Sukhikh Gennady T.
Published: April 2021

Despite the differences in the clinical manifestations of major obstetric syndromes, such as preeclampsia (PE) and intrauterine growth restriction (IUGR), their pathogenesis is based on the dysregulation of proliferation, differentiation, and invasion of cytotrophoblast cells that occur in the developing placenta, decidual endometrium, and myometrial parts of the spiral arteries. To understand the similarities and differences in the molecular mechanisms of PE and IUGR, samples of the placental bed and placental tissue were analyzed using protein mass spectrometry and the deep sequencing of small RNAs, followed by validation of the data obtained by quantitative RT-PCR in real time. A comparison of the transcriptome and proteomic profiles in the samples made it possible to conclude that the main changes in the molecular profile in IUGR occur in the placental bed, in contrast to PE, in which the majority of molecular changes occurs in the placenta. In placental bed samples, significant changes in the ratio of miRNA and its potential target gene expression levels were revealed, which were unique for IUGR (miR-30c-5p/VIM, miR-28-3p/VIM, miR-1-3p/ANXA2, miR-30c-5p/FBN1; miR-15b-5p/MYL6), unique for PE (miR-185-3p/FLNA), common for IUGR and PE (miR-30c-5p/YWHAZ and miR-654-3p/FGA), but all associated with abnormality in the hemostatic and vascular systems as well as with an inflammatory process at the fetal‒maternal interface.
Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis
Authors: Gould Lisa J. , Serena Thomas E. , Sinha Smeeta
Published: April 2021

Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe form of vascular calcification with no approved therapies. A standardized wound assessment tool is needed to evaluate changes in calciphylaxis wounds over time. A prospective, single-arm study of 14 patients with calciphylaxis reported improvement for the primary endpoint of wound healing using the 13-item Bates-Jensen Wound Assessment Tool (BWAT), although that tool was developed for assessment of pressure ulcers. This report describes development of BWAT-CUA, an 8-item modification of BWAT focusing on prototypical features of calciphylaxis lesions. The BWAT-CUA has a range of 8 (best) to 40 (worst) and was used ad hoc to analyze BWAT data collected in the prospective study. Using BWAT-CUA, relative improvement in calciphylaxis wounds was 30% overall (from 21.2 to 14.9; p = 0.0016) and 34% in the subset of 12 patients with ulceration at baseline (from 23.3 to 15.3; p = 0.0002). BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice.
Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients
Authors: Trandafir Laura Mihaela , Cojocaru Elena , Moscalu Mihaela , Leon Constantin Maria Magdalena , Miron Ingrith , Mastaleru Alexandra , Teslariu Oana , Datcu Madalina Elena , Fotea Silvia , Frăsinariu Otilia
Published: April 2021

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.
Numerical Simulation Study on Flow Laws and Heat Transfer of Gas Hydrate in the Spiral Flow Pipeline with Long Twisted Band
Authors: Rao Yongchao , Li Lijun , Wang Shuli , Zhao Shuhua , Zhou Shidong
Published: April 2021

The natural gas hydrate plugging problems in the mixed pipeline are becoming more and more serious. The hydrate plugging has gradually become an important problem to ensure the safety of pipeline operation. The deposition and heat transfer characteristics of natural gas hydrate particles in the spiral flow pipeline have been studied. The DPM model (discrete phase model) was used to simulate the motion of solid particles, which was used to simulate the complex spiral flow characteristics of hydrate in the pipeline with a long twisted band. The deposition and heat transfer characteristics of gas hydrate particles in the spiral flow pipeline were studied. The velocity distribution, pressure drop distribution, heat transfer characteristics, and particle settling characteristics in the pipeline were investigated. The numerical results showed that compared with the straight flow without a long twisted band, two obvious eddies are formed in the flow field with a long twisted band, and the velocities are maximum at the center of the vortices. Along the direction of the pipeline, the two vortices move toward the pipe wall from near the twisted band, which can effectively carry the hydrate particles deposited on the wall. With the same Reynolds number, the twisted rate was greater, the spiral strength was weaker, the tangential velocity was smaller, and the pressure drop was smaller. Therefore, the pressure loss can be reduced as much as possible with effect of the spiral flow. In a straight light flow, the Nusselt number is in a parabolic shape with the opening downwards. At the center of the pipe, the Nusselt number gradually decreased toward the pipe wall at the maximum, and at the near wall, the attenuation gradient of the Nu number was large. For spiral flow, the curve presented by the Nusselt number was a trough at the center of the pipe and a peak at 1/2 of the pipe diameter. With the reduction of twist rate, the Nusselt number becomes larger. Therefore, the spiral flow can make the temperature distribution more even and prevent the large temperature difference, resulting in the mass formation of hydrate particles in the pipeline wall. Spiral flow has a good carrying effect. Under the same condition, the spiral flow carried hydrate particles at a distance about 3–4 times farther than that of the straight flow.