bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Mechanisms Regulating Obesity-Associated Hepatocellular Carcinoma
Authors: Rajesh Yetirajam , Sarkar Devanand
Published: May 2020

Obesity is a global, intractable issue, altering inflammatory and stress response pathways, and promoting tissue adiposity and tumorigenesis. Visceral fat accumulation is correlated with primary tumor recurrence, poor prognosis and chemotherapeutic resistance. Accumulating evidence highlights a close association between obesity and an increased incidence of hepatocellular carcinoma (HCC). Obesity drives HCC, and obesity-associated tumorigenesis develops via nonalcoholic fatty liver (NAFL), progressing to nonalcoholic steatohepatitis (NASH) and ultimately to HCC. The better molecular elucidation and proteogenomic characterization of obesity-associated HCC might eventually open up potential therapeutic avenues. The mechanisms relating obesity and HCC are correlated with adipose tissue remodeling, alteration in the gut microbiome, genetic factors, ER stress, oxidative stress and epigenetic changes. During obesity-related hepatocarcinogenesis, adipokine secretion is dysregulated and the nuclear factor erythroid 2 related factor 1 (Nrf-1), nuclear factor kappa B (NF-κB), mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways are activated. This review captures the present trends allied with the molecular mechanisms involved in obesity-associated hepatic tumorigenesis, showcasing next generation molecular therapeutic strategies and their mechanisms for the successful treatment of HCC.
Rho GTPases in Gynecologic Cancers: In-Depth Analysis toward the Paradigm Change from Reactive to Predictive, Preventive, and Personalized Medical Approach Benefiting the Patient and Healthcare
Authors: Zubor Pavol , Dankova Zuzana , Kolkova Zuzana , Holubekova Veronika , Brany Dusan , Mersakova Sandra , Samec Marek , Liskova Alena , Koklesova Lenka , Kubatka Peter , Bujnak Jan , Kajo Karol , Mlyncek Milos , Giordano Frank A. , Golubnitschaja Olga
Published: May 2020

Rho guanosine triphospatases (GTPases) resemble a conserved family of GTP-binding proteins regulating actin cytoskeleton dynamics and several signaling pathways central for the cell. Rho GTPases create a so-called Ras-superfamily of GTPases subdivided into subgroups comprising at least 20 members. Rho GTPases play a key regulatory role in gene expression, cell cycle control and proliferation, epithelial cell polarity, cell migration, survival, and apoptosis, among others. They also have tissue-related functions including angiogenesis being involved in inflammatory and wound healing processes. Contextually, any abnormality in the Rho GTPase function may result in severe consequences at molecular, cellular, and tissue levels. Rho GTPases also play a key role in tumorigenesis and metastatic disease. Corresponding mechanisms include a number of targets such as kinases and scaffold/adaptor-like proteins initiating GTPases-related signaling cascades. The accumulated evidence demonstrates the oncogenic relevance of Rho GTPases for several solid malignancies including breast, liver, bladder, melanoma, testicular, lung, central nervous system (CNS), head and neck, cervical, and ovarian cancers. Furthermore, Rho GTPases play a crucial role in the development of radio- and chemoresistance e.g. under cisplatin-based cancer treatment. This article provides an in-depth overview on the role of Rho GTPases in gynecological cancers, highlights relevant signaling pathways and pathomechanisms, and sheds light on their involvement in tumor progression, metastatic spread, and radio/chemo resistance. In addition, insights into a spectrum of novel biomarkers and innovative approaches based on the paradigm shift from reactive to predictive, preventive, and personalized medicine are provided.
Common and Differential Traits of the Membrane Lipidome of Colon Cancer Cell Lines and Their Secreted Vesicles: Impact on Studies Using Cell Lines
Authors: Bestard-Escalas Joan , Maimó-Barceló Albert , Lopez Daniel H. , Reigada Rebeca , Guardiola-Serrano Francisca , Ramos-Vivas José , Hornemann Thorsten , Okazaki Toshiro , Barceló-Coblijn Gwendolyn
Published: May 2020

Colorectal cancer (CRC) is the fourth leading cause of cancer death in the world. Despite the screening programs, its incidence in the population below the 50s is increasing. Therefore, new stratification protocols based on multiparametric approaches are highly needed. In this scenario, the lipidome is emerging as a powerful tool to classify tumors, including CRC, wherein it has proven to be highly sensitive to cell malignization. Hence, the possibility to describe the lipidome at the level of lipid species has renewed the interest to investigate the role of specific lipid species in pathologic mechanisms, being commercial cell lines, a model still heavily used for this purpose. Herein, we characterize the membrane lipidome of five commercial colon cell lines and their extracellular vesicles (EVs). The results demonstrate that both cell and EVs lipidome was able to segregate cells according to their malignancy. Furthermore, all CRC lines shared a specific and strikingly homogenous impact on ether lipid species. Finally, this study also cautions about the need of being aware of the singularities of each cell line at the level of lipid species. Altogether, this study firmly lays the groundwork of using the lipidome as a solid source of tumor biomarkers.
A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma
Authors: Fujisawa Toshio , Shimamura Takeshi , Goto Kaku , Nakagawa Ryo , Muroyama Ryosuke , Ino Yoshinori , Horiuchi Hajime , Endo Itaru , Maeda Shin , Harihara Yasushi , Nakajima Atsushi , Matsuhashi Nobuyuki , Kato Naoya , Isayama Hiroyuki , Puri Ankit , Suzuki Akiko , Bellayr Ian , Leland Pamela , Joshi Bharat H. , Puri Raj K.
Published: May 2020

Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13Rα2) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 –ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13Rα2 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.
α-Functionalization of Imines via Visible Light Photoredox Catalysis
Authors: Garrido-Castro Alberto F. , Maestro M. Carmen , Alemán José
Published: May 2020

The innate electrophilicity of imine building blocks has been exploited in organic synthetic chemistry for decades. Inspired by the resurgence in photocatalysis, imine reactivity has now been redesigned through the generation of unconventional and versatile radical intermediates under mild reaction conditions. While novel photocatalytic approaches have broadened the range and applicability of conventional radical additions to imine acceptors, the possibility to use these imines as latent nucleophiles via single-electron reduction has also been uncovered. Thus, multiple research programs have converged on this issue, delivering creative and practical strategies to achieve racemic and asymmetric α-functionalizations of imines under visible light photoredox catalysis.
Critical Issues and Guidelines to Improve the Performance of Photocatalytic Polymeric Membranes
Authors: Romay Marta , Diban Nazely , Rivero Maria J. , Urtiaga Ane , Ortiz Inmaculada
Published: May 2020

Photocatalytic membrane reactors (PMR), with immobilized photocatalysts, play an important role in process intensification strategies; this approach offers a simple solution to the typical catalyst recovery problem of photocatalytic processes and, by simultaneous filtration and photocatalysis of the aqueous streams, facilitates clean water production in a single unit. The synthesis of polymer photocatalytic membranes has been widely explored, while studies focused on ceramic photocatalytic membranes represent a minority. However, previous reports have identified that the successful synthesis of polymeric photocatalytic membranes still faces certain challenges that demand further research, e.g., (i) reduced photocatalytic activity, (ii) photocatalyst stability, and (iii) membrane aging, to achieve technological competitiveness with respect to suspended photocatalytic systems. The novelty of this review is to go a step further to preceding literature by first, critically analyzing the factors behind these major limitations and second, establishing useful guidelines. This information will help researchers in the field in the selection of the membrane materials and synthesis methodology for a better performance of polymeric photocatalytic membranes with targeted functionality; special attention is focused on factors affecting membrane aging and photocatalyst stability.
Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction
Authors: Liu Ming-Che , Chang Meng-Lin , Wang Ya-Chun , Chen Wei-Hung , Wu Chien-Chih , Yeh Shauh-Der
Published: May 2020

Erectile dysfunction (ED) is an inability to attain or maintain adequate penile erection for successful vaginal intercourse, leading to sexual and relationship dissatisfaction. To combat ED, various surgical and non-surgical approaches have been developed in the past to restore erectile functions. These therapeutic interventions exhibit significant impact in providing relief to patients; however, due to their associated adverse effects and lack of long-term efficacy, newer modalities such as regenerative therapeutics have gained attention due to their safe and prolonged efficacy. Stem cells and platelet-derived biomaterials contained in platelet-rich plasma (PRP) are thriving as some of the major therapeutic regenerative agents. In recent years, various preclinical and clinical studies have evaluated the individual, as well as combined of stem cells and PRP to restore erectile function. Being rich in growth factors, chemokines, and angiogenic factors, both stem cells and PRP play a crucial role in regenerating nerve cells, myelination of axons, homing and migration of progenitor cells, and anti-fibrosis and anti-apoptosis of damaged cavernous nerve in corporal tissues. Further, platelet-derived biomaterials have been proven to be a biological supplement for enhancing the proliferative and differentiation potential of stem cells towards neurogenic fate. Therefore, this article comprehensively analyzes the progresses of these regenerative therapies for ED.
Targeting PI3K and AMPKα Signaling Alone or in Combination to Enhance Radiosensitivity of Triple Negative Breast Cancer
Authors: Johnson Jeremy , Chow Zeta , Napier Dana , Lee Eun , Weiss Heidi L. , Evers B. Mark , Rychahou Piotr
Published: May 2020

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is characterized by poor survival. Radiotherapy plays an important role in treating TNBC. The purpose of this study was to determine whether inhibiting the AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3K) pathways alone or in combination potentiates radiotherapy in TNBC. AMPKα1 and AMPKα2 knockdown diminished cyclin D1 expression and induced G1 cell cycle arrest but did not induce apoptosis alone or in combination with radiotherapy. Next, we analyzed the role of PI3K p85α, p85β, p110α, p110β, Akt1, and Akt2 proteins on TNBC cell cycle progression and apoptosis induction. Akt1 and p110α knockdown diminished cyclin D1 expression and induced apoptosis. Silencing Akt1 promoted synergistic apoptosis induction during radiotherapy and further reduced survival after radiation. Treatment with the Akt inhibitor, MK-2206 48 h after radiotherapy decreased Akt1 levels and potentiated radiation-induced apoptosis. Together, our results demonstrate that AMPKα, p110α, and Akt1 promote TNBC proliferation and that Akt1 is a key regulator of radiosensitivity in TNBC. Importantly, combining radiotherapy with the pharmacological inhibition of Akt1 expression is a potentially promising approach for the treatment of TNBC.
Phosphodiesterase 4B: Master Regulator of Brain Signaling
Authors: Tibbo Amy J. , Baillie George S.
Published: May 2020

Phosphodiesterases (PDEs) are the only superfamily of enzymes that have the ability to break down cyclic nucleotides and, as such, they have a pivotal role in neurological disease and brain development. PDEs have a modular structure that allows targeting of individual isoforms to discrete brain locations and it is often the location of a PDE that shapes its cellular function. Many of the eleven different families of PDEs have been associated with specific diseases. However, we evaluate the evidence, which suggests the activity from a sub-family of the PDE4 family, namely PDE4B, underpins a range of important functions in the brain that positions the PDE4B enzymes as a therapeutic target for a diverse collection of indications, such as, schizophrenia, neuroinflammation, and cognitive function.
Digital Spindle: A New Way to Explore Mitotic Functions by Whole Cell Data Collection and a Computational Approach
Authors: Yamashita Norio , Morita Masahiko , Yokota Hideo , Mimori-Kiyosue Yuko
Published: May 2020

From cells to organisms, every living system is three-dimensional (3D), but the performance of fluorescence microscopy has been largely limited when attempting to obtain an overview of systems’ dynamic processes in three dimensions. Recently, advanced light-sheet illumination technologies, allowing drastic improvement in spatial discrimination, volumetric imaging times, and phototoxicity/photobleaching, have been making live imaging to collect precise and reliable 3D information increasingly feasible. In particular, lattice light-sheet microscopy (LLSM), using an ultrathin light-sheet, enables whole-cell 3D live imaging of cellular processes, including mitosis, at unprecedented spatiotemporal resolution for extended periods of time. This technology produces immense and complex data, including a significant amount of information, raising new challenges for big image data analysis and new possibilities for data utilization. Once the data are digitally archived in a computer, the data can be reused for various purposes by anyone at any time. Such an information science approach has the potential to revolutionize the use of bioimage data, and provides an alternative method for cell biology research in a data-driven manner. In this article, we introduce examples of analyzing digital mitotic spindles and discuss future perspectives in cell biology.
Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E2 Activation in Human Podocytes
Authors: Mangelsen Eva , Rothe Michael , Schulz Angela , Kourpa Aikaterini , Panáková Daniela , Kreutz Reinhold , Bolbrinker Juliane
Published: May 2020

Glomerular hyperfiltration is an important mechanism in the development of albuminuria. During hyperfiltration, podocytes are exposed to increased fluid flow shear stress (FFSS) in Bowman’s space. Elevated Prostaglandin E2 (PGE2) synthesis and upregulated cyclooxygenase 2 (Cox2) are associated with podocyte injury by FFSS. We aimed to elucidate a PGE2 autocrine/paracrine pathway in human podocytes (hPC). We developed a modified liquid chromatography tandem mass spectrometry (LC/ESI-MS/MS) protocol to quantify cellular PGE2, 15-keto-PGE2, and 13,14-dihydro-15-keto-PGE2 levels. hPC were treated with PGE2 with or without separate or combined blockade of prostaglandin E receptors (EP), EP2, and EP4. Furthermore, the effect of FFSS on COX2, PTGER2, and PTGER4 expression in hPC was quantified. In hPC, stimulation with PGE2 led to an EP2- and EP4-dependent increase in cyclic adenosine monophosphate (cAMP) and COX2, and induced cellular PGE2. PTGER4 was downregulated after PGE2 stimulation in hPC. In the corresponding LC/ESI-MS/MS in vivo analysis at the tissue level, increased PGE2 and 15-keto-PGE2 levels were observed in isolated glomeruli obtained from a well-established rat model with glomerular hyperfiltration, the Munich Wistar Frömter rat. COX2 and PTGER2 were upregulated by FFSS. Our data thus support an autocrine/paracrine COX2/PGE2 pathway in hPC linked to concerted EP2 and EP4 signaling.
Contribution of a GATA4-Expressing Hematopoietic Progenitor Lineage to the Adult Mouse Endothelium
Authors: Carmona Rita , Díaz del Moral Sandra , Barrena Silvia , Muñoz-Chápuli Ramón
Published: May 2020

Different sources have been claimed for the embryonic origin of the coronary endothelium. Recently, the potential of circulating cells as progenitors of the cardiac endothelium has also been suggested. In a previous study we have shown that circulating progenitors are recruited by the embryonic endocardium and incorporated into the coronary vessels. These progenitors derive from a mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2. Herein, we aim to trace this specific lineage throughout postnatal stages. We have found that more than 50% of the adult cardiac endothelium derives from the G2-GATA4 lineage. This percentage increases from embryos to adults probably due to differential proliferation and postnatal recruitment of circulating endothelial progenitors. In fact, injection of fetal liver or placental cells in the blood stream of neonates leads to incorporation of G2-GATA4 lineage cells to the coronary endothelium. On the other hand, labeling of the hematopoietic lineage by the stage E7.5 also resulted in positive coronary endothelial cells from both, embryos and adults. Our results suggest that early hematopoietic progenitors recruited by the embryonic ventricular endocardium can become the predominant source of definitive endothelium during the vascularization of the heart.
The Role of Caspase-2 in Regulating Cell Fate
Authors: Vigneswara Vasanthy , Ahmed Zubair
Published: May 2020

Caspase-2 is the most evolutionarily conserved member of the mammalian caspase family and has been implicated in both apoptotic and non-apoptotic signaling pathways, including tumor suppression, cell cycle regulation, and DNA repair. A myriad of signaling molecules is associated with the tight regulation of caspase-2 to mediate multiple cellular processes far beyond apoptotic cell death. This review provides a comprehensive overview of the literature pertaining to possible sophisticated molecular mechanisms underlying the multifaceted process of caspase-2 activation and to highlight its interplay between factors that promote or suppress apoptosis in a complicated regulatory network that determines the fate of a cell from its birth and throughout its life.
DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines
Authors: D’Amico Silvia , Krasnowska Ewa , Manni Isabella , Toietta Gabriele , Baldari Silvia , Piaggio Giulia , Ranalli Marco , Gambacurta Alessandra , Vernieri Claudio , Di Giacinto Flavio , Bernassola Francesca , de Braud Filippo , Lucibello Maria
Published: May 2020

Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy. Increased levels of the phosphorylated form of Translationally Controlled Tumour Protein (phospho-TCTP) have been shown to be associated with a poor clinical response to trastuzumab therapy in HER2-positive breast cancer. Here we show that phospho-TCTP is essential for correct mitosis in human mammary epithelial cells. Reduction of phospho-TCTP levels by dihydroartemisinin (DHA) causes mitotic aberration and increases microtubule density in the trastuzumab-resistant breast cancer cells HCC1954 and HCC1569. Combinatorial studies show that T-DM1 when combined with DHA is more effective in killing breast cells compared to the effect induced by any single agent. In an orthotopic breast cancer xenograft model (HCC1954), the growth of the tumour cells resumes after having achieved a complete response to T-DM1 treatment. Conversely, DHA and T-DM1 treatment induces a severe and irreversible cytotoxic effect, even after treatment interruption, thus, improving the long-term efficacy of T-DM1. These results suggest that DHA increases the effect of T-DM1 as poison for microtubules and supports the clinical development of the combination of DHA and T-DM1 for the treatment of aggressive HER2-overexpressing breast cancer.
IGFBP-3/IGFBP-3 Receptor System as an Anti-Tumor and Anti-Metastatic Signaling in Cancer
Authors: Cai Qing , Dozmorov Mikhail , Oh Youngman
Published: May 2020

Insulin-like growth factor binding protein-3 (IGFBP-3) is a p53 tumor suppressor-regulated protein and a major carrier for IGFs in circulation. Among six high-affinity IGFBPs, which are IGFBP-1 through 6, IGFBP-3 is the most extensively investigated IGFBP species with respect to its IGF/IGF-I receptor (IGF-IR)-independent biological actions beyond its endocrine/paracrine/autocrine role in modulating IGF action in cancer. Disruption of IGFBP-3 at transcriptional and post-translational levels has been implicated in the pathophysiology of many different types of cancer including breast, prostate, and lung cancer. Over the past two decades, a wealth of evidence has revealed both tumor suppressing and tumor promoting effects of IGF/IGF-IR-independent actions of IGFBP-3 depending upon cell types, post-translational modifications, and assay methods. However, IGFBP-3′s anti-tumor function has been well accepted due to identification of functional IGFBP-3-interacting proteins, putative receptors, or crosstalk with other signaling cascades. This review mainly focuses on transmembrane protein 219 (TMEM219), which represents a novel IGFBP-3 receptor mediating antitumor effect of IGFBP-3. Furthermore, this review delineates the potential underlying mechanisms involved and the subsequent biological significance, emphasizing the clinical significance of the IGFBP-3/TMEM219 axis in assessing both the diagnosis and the prognosis of cancer as well as the therapeutic potential of TMEM219 agonists for cancer treatment.
Erratum: Bharti D., et al. In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded. Cells 2020, 9, 557
Authors: Bharti Dinesh , Jang Si-Jung , Lee Sang-Yun , Lee Sung-Lim , Rho Gyu-Jin
Published: May 2020

The wrong grant number was erroneously entered in the original manuscript and needs to be changed from NRF-2017R1D1A1B03035677 to NRF-2019R1I1A3A01060073 in [...]
GPS-PBS: A Deep Learning Framework to Predict Phosphorylation Sites that Specifically Interact with Phosphoprotein-Binding Domains
Authors: Guo Yaping , Ning Wanshan , Jiang Peiran , Lin Shaofeng , Wang Chenwei , Tan Xiaodan , Yao Lan , Peng Di , Xue Yu
Published: May 2020

Protein phosphorylation is essential for regulating cellular activities by modifying substrates at specific residues, which frequently interact with proteins containing phosphoprotein-binding domains (PPBDs) to propagate the phosphorylation signaling into downstream pathways. Although massive phosphorylation sites (p-sites) have been reported, most of their interacting PPBDs are unknown. Here, we collected 4458 known PPBD-specific binding p-sites (PBSs), considerably improved our previously developed group-based prediction system (GPS) algorithm, and implemented a deep learning plus transfer learning strategy for model training. Then, we developed a new online service named GPS-PBS, which can hierarchically predict PBSs of 122 single PPBD clusters belonging to two groups and 16 families. By comparison, GPS-PBS achieved a highly competitive accuracy against other existing tools. Using GPS-PBS, we predicted 371,018 mammalian p-sites that potentially interact with at least one PPBD, and revealed that various PPBD-containing proteins (PPCPs) and protein kinases (PKs) can simultaneously regulate the same p-sites to orchestrate important pathways, such as the PI3K-Akt signaling pathway. Taken together, we anticipate GPS-PBS can be a great help for further dissecting phosphorylation signaling networks.
Activated Cardiac Fibroblasts Control Contraction of Human Fibrotic Cardiac Microtissues by a β-Adrenoreceptor-Dependent Mechanism
Authors: Błyszczuk Przemysław , Zuppinger Christian , Costa Ana , Nurzynska Daria , Di Meglio Franca , Stellato Mara , Agarkova Irina , Smith Godfrey , Distler Oliver , Kania Gabriela
Published: May 2020

Cardiac fibrosis represents a serious clinical problem. Development of novel treatment strategies is currently restricted by the lack of the relevant experimental models in a human genetic context. In this study, we fabricated self-aggregating, scaffold-free, 3D cardiac microtissues using human inducible pluripotent stem cell (iPSC)-derived cardiomyocytes and human cardiac fibroblasts. Fibrotic condition was obtained by treatment of cardiac microtissues with profibrotic cytokine transforming growth factor β1 (TGF-β1), preactivation of foetal cardiac fibroblasts with TGF-β1, or by the use of cardiac fibroblasts obtained from heart failure patients. In our model, TGF-β1 effectively induced profibrotic changes in cardiac fibroblasts and in cardiac microtissues. Fibrotic phenotype of cardiac microtissues was inhibited by treatment with TGF-β-receptor type 1 inhibitor SD208 in a dose-dependent manner. We observed that fibrotic cardiac microtissues substantially increased the spontaneous beating rate by shortening the relaxation phase and showed a lower contraction amplitude. Instead, no changes in action potential profile were detected. Furthermore, we demonstrated that contraction of human cardiac microtissues could be modulated by direct electrical stimulation or treatment with the β-adrenergic receptor agonist isoproterenol. However, in the absence of exogenous agonists, the β-adrenoreceptor blocker nadolol decreased beating rate of fibrotic cardiac microtissues by prolonging relaxation time. Thus, our data suggest that in fibrosis, activated cardiac fibroblasts could promote cardiac contraction rate by a direct stimulation of β-adrenoreceptor signalling. In conclusion, a model of fibrotic cardiac microtissues can be used as a high-throughput model for drug testing and to study cellular and molecular mechanisms of cardiac fibrosis.
Advances of Single-Cell Protein Analysis
Authors: Liu Lixing , Chen Deyong , Wang Junbo , Chen Jian
Published: May 2020

Proteins play a significant role in the key activities of cells. Single-cell protein analysis provides crucial insights in studying cellular heterogeneities. However, the low abundance and enormous complexity of the proteome posit challenges in analyzing protein expressions at the single-cell level. This review summarizes recent advances of various approaches to single-cell protein analysis. We begin by discussing conventional characterization approaches, including fluorescence flow cytometry, mass cytometry, enzyme-linked immunospot assay, and capillary electrophoresis. We then detail the landmark advances of microfluidic approaches for analyzing single-cell protein expressions, including microfluidic fluorescent flow cytometry, droplet-based microfluidics, microwell-based assay (microengraving), microchamber-based assay (barcoding microchips), and single-cell Western blotting, among which the advantages and limitations are compared. Looking forward, we discuss future research opportunities and challenges for multiplexity, analyte, throughput, and sensitivity of the microfluidic approaches, which we believe will prompt the research of single-cell proteins such as the molecular mechanism of cell biology, as well as the clinical applications for tumor treatment and drug development.
Secretome of Mesenchymal Stromal Cells Prevents Myofibroblasts Differentiation by Transferring Fibrosis-Associated microRNAs within Extracellular Vesicles
Authors: Basalova Nataliya , Sagaradze Georgy , Arbatskiy Mikhail , Evtushenko Evgeniy , Kulebyakin Konstantin , Grigorieva Olga , Akopyan Zhanna , Kalinina Natalia , Efimenko Anastasia
Published: May 2020

Fibroblasts differentiation into myofibroblasts is a central event of tissue fibrosis. Multipotent mesenchymal stromal cells (MSCs) secretome can interfere with fibrosis development; despite precise underlying mechanisms remain unclear. In this study, we tested the hypothesis that MSC secretome can affect fibroblast’ differentiation into myofibroblasts by delivering regulatory RNAs, including microRNAs to these cells. Using the model of transforming growth factor-beta (TGFbeta)-induced fibroblast differentiation into myofibroblasts, we tested the activity of human MSC secretome components, specifically extracellular vesicles (MSC-EV). We showed that MSC-EV down-regulated secretion of extracellular matrix proteins by fibroblasts as well as suppressed their contractility resulting in prevention as well as reversion of fibroblasts differentiation to myofibroblasts. High-throughput sequencing of RNAs extracted from MSC-EV has revealed many fibrosis-associated microRNAs. Fibroblast treatment with MSC-EV led to direct transfer of microRNAs, which resulted in the elevation of most prominent fibrosis-associated microRNAs, including microRNA-21 and microRNA-29c. Using MSC-EV transfection by antagomirs to these microRNAs we demonstrated their involvement in the suppression of fibroblast differentiation in our model. Taken together, MSC secretome can suppress fibrosis by prevention of fibroblast differentiation into myofibroblasts as well as induce de-differentiation of the latter by direct transfer of specific microRNAs.
Scanning Kelvin Probe Investigation of High-Strength Steel Surface after Impact of Hydrogen and Tensile Strain
Authors: Nazarov Andrei , Vucko Flavien , Thierry Dominique
Published: May 2020

Hydrogen in combination with mechanical stress can lead to rapid degradation of high-strength steels through environmentally assisted cracking mechanisms. The scanning Kelvin probe (SKP) was applied to automotive martensitic steel grade MS1500 in order to detect local reactivity of the surface after hydrogen uptake and tensile deformation. Hydrogen and stress distribution in microstructures can be characterized by SKP indirectly measuring the potential drop in the surface oxide. Thus, the links between electron work function, oxide condition, and subsurface accumulation of hydrogen and stress have to be investigated. It was shown that plastic strain can mechanically break down the oxide film creating active (low potential) locations. Hydrogen effusion from the steel bulk, after cathodic charging in aqueous electrolyte, reduced the surface oxide and also decreased potential. It was shown that surface re-oxidation was delayed as a function of the current density and duration of cathodic hydrogen pre-charging. Thus, potential evolution during exposure in air can characterize the relative amount of subsurface hydrogen. SKP mapping of martensitic microstructure with locally developed residual stress and accumulated hydrogen displayed the lowest potential.
Experimental Study of the Influence of Deposition of Multilayer CrN/CrCN PVD Coating on Austenitic Steel on Resistance to Cavitation Erosion
Authors: Krella Alicja K. , Czyzniewski Andrzej , Gilewicz Adam , Gajowiec Grzegorz
Published: May 2020

The impact of deposition of multilayer CrN/CrCN coating on X6CrNiTi18-10 steel by means of the PVD (physical vapour deposition) method on resistance to cavitation erosion has been investigated. Cavitation tests were performed using a cavitation chamber with a barricade system at the inlet pressure p1 = 600 kPa and the outlet pressure p2 = 123 kPa. Deposition of CrN/CrCN coating allowed increasing duration of the incubation period and decreasing cumulative volume loss until 500 min of exposure. The erosion of the CrN/CrCN–X6CrNiTi18-10 system begins with the removal of microdroplets from the coating surface and surface undulation. The surface undulation increases with the exposure time leading to coating fracture in a brittle mode. Initiation sites of cracks were located inside the PVD coating. Measurements of surface roughness illustrate uneven degradation of the exposed surface and the location of slight and severe erosion zones. The Ra parameters obtained for the CrN/CrCN–X6CrNiTi18-10 system and X6CrNiTi18-10 steel after 180 min of erosion were comparable. An elongation of erosion test up to 600 min resulted in a higher increase in surface roughness of the CrN/CrCN coating–X6CrNiTi18-10 steel system in comparison to that of X6CrNiTi18-10 steel. With increasing exposition time, the rate of increase of the surface roughness decreased due to overlapping damage.
Effect of Modified Hexagonal Boron Nitride Nanoparticles on the Emulsion Stability, Viscosity and Electrochemical Behavior of Nanostructured Acrylic Coatings for the Corrosion Protection of AISI 304 Stainless Steel
Authors: Ysiwata-Rivera Alma P. , Hernández-Hernández Ernesto , Cadenas-Pliego Gregorio , Ávila-Orta Carlos A. , González-Morones Pablo , Jesús Juan A. Velásquez-de , Cuara-Díaz Edgar , Gallardo-Vega Carlos A. , Mata-Padilla José M.
Published: May 2020

In this study, the effect of pure and modified hexagonal boron nitride (h-BN) nanosheet incorporation on the stability, viscosity, and electrochemical behavior of a waterborne emulsion acrylic coating was studied. The functionalization of h-BN nanoplatelets with polyacrylic acid (PAA) plasma polymerization was performed, and the successful surface modification was determined through water dispersion testing, Fourier transform infrared spectroscopy and thermogravimetric analysis, X-ray photoelectron spectroscopy, and also by transmission electronic microscopy. Later, the stability and viscosity properties of emulsion nanostructured acrylic coatings, which were previously prepared by an ultrasound-assisted mixing system, were analyzed using zeta potential and rheometry testing, respectively. The electrochemical behavior was analyzed by electrochemical impedance spectroscopy. The results prove an effective deposition of PAA films on the h-BN surfaces, which enhanced the stability and viscosity acrylic of nanostructured coatings due to the interactions between the h-BN nanoplatelets surface and emulsion acrylic paint and also with the thickener additives. On the other hand, the electrochemical analysis demonstrated a significant increase (two orders of magnitude) in corrosion resistance in the acrylic nanostructured coatings with 1 wt.% of unmodified and modified h-BN nanoplatelets concerning pure acrylic paint due to a barrier protection mechanism of corrosion inhibition. Therefore, the results demonstrate that the surface modification of h-BN by plasma polymerization (green technology) helped to solve the low dispersibility issue of BN nanosheet surfaces in a waterborne polymer matrix to obtained green nanostructured acrylic coatings with the right balance in in-can properties and corrosion inhibition of AISI 304 stainless steel.
Influence of AlN and GaN Pulse Ratios in Thermal Atomic Layer Deposited AlGaN on the Electrical Properties of AlGaN/GaN Schottky Diodes
Authors: Kim Hogyoung , Choi Seok , Choi Byung Joon
Published: May 2020

Atomic layer deposited AlGaN with different AlN and GaN pulse ratios (2:1, 1:1, and 1:2) was used to prepare AlGaN/GaN Schottky diodes, and their current transport mechanisms were investigated using current–voltage (I–V) and capacitance–voltage (C–V) measurements. Under low reverse bias condition, the sample with the pulse ratio of 2:1 was explained by Poole–Frenkel emission and the negative temperature dependence for the sample with the pulse ratio of 1:2 was associated with the acceptor levels in the AlGaN layer. Fast interface traps at 0.24–0.29 eV were observed for the samples with the pulse ratios of 1:1 and 1:2, whereas bulk traps at ~0.34 eV were observed for the sample with the pulse ratio of 2:1. Higher trap densities were obtained from the C–V hysteresis measurements when the pulse ratios were 1:1 and 1:2, indicating the presence of a charge trapping interfacial layer. According to the X-ray photoelectron spectroscopy spectra, the pulse ratio of 2:1 was found to have less oxygen-related defects in the AlGaN layer.
Evaluation of Experimental Multi-Particulate Polymer-Coated Drug Delivery Systems with Meloxicam
Authors: Hîrjău Mircea , Miron Dalia Simona , Anuța Valentina , Lupuliasa Dumitru , Ghica Mihaela Violeta , Jinga Viorel , Dinu-Pîrvu Cristina-Elena
Published: May 2020

The objectives of this study are the development and evaluation of modified release multi-particulate drug delivery systems containing a BCS class II drug (meloxicam), formulated as polymer-coated pellets. Inert seeds containing microcrystalline cellulose, lactose monohydrate, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The obtained cores were loaded with meloxicam using the drug layering technique, by spray coating in a fluidized bed with a liquid dispersion of the drug. The resulting drug pellets were film-coated with various polymers (Acryl-EZE® 93O, Eudragit® RS 30-D as well as experimental composite obtained by adding Methocel™ E5 Premium LV as pore forming agent to the extended release polymer Eudragit® RS 30-D). All experimental systems were evaluated by scanning electron microscopy and in vitro release testing, in an attempt to investigate the characteristics of the film coatings and their influence on drug release from the multi-particulate systems. The in vitro release study was performed in two stages, using two media with pH values corresponding to the gastric and intestinal environment (HCl 0.1N, pH = 1.2 for the first two hours of the test and phosphate buffer 50 mM, pH 6.8 for the next 4 h). The in vitro release data have highlighted the impact of the formulation factors on the drug release.
Surface Modification of the Ti-6Al-4V Alloy by Anodic Oxidation and Its Effect on Osteoarticular Cell Proliferation
Authors: Torres-Avila Itzel P. , Padilla-Martínez Itzia I. , Pérez-Hernández Nury , Bañuelos-Hernández Angel E. , Velázquez Julio C. , Castrejón-Flores José L. , Hernández-Sánchez Enrique
Published: May 2020

This investigation describes the formation of crystalline nanotubes of titanium oxide on the surface of a Ti-6Al-4V alloy and its biological evaluation. The formation of nanotubes was performed by the anodic oxidation technique with a constant work potential of 60 V but with different anodizing times of 10, 20, 30, 40, 50, and 60 min used to evaluate their effects on the characteristics of the nanotubes and their biological activity. A mixture of ethylene glycol, water, and ammonium fluoride (NH4F) was used as the electrolytic fluid. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were applied to determine the morphology and crystalline nature of the nanotubes, showing a well-defined matrix of nanotubes of titanium oxide with a crystalline structure and a diameter in the range of 52.5 ± 5.13 to 95 ± 11.92 nm. In contrast, the XRD patterns showed an increase of defined peaks that directly correlated with treatment times. Moreover, in vitro assays using an innovative cell culture device demonstrated that the inner diameter of the nanotubes directly correlated with cell proliferation.
Chromium Diffusion Coating on an ODS Ferritic-Martensitic Steel and Its Oxidation Behavior in Air and Steam Environments
Authors: Kim Chaewon , Kim Sung Hwan , Cha Ji-Hwan , Jang Changheui , Kim Tae Kyu
Published: May 2020

A chromium diffusion coating was applied on an oxide dispersion strengthened ferritic-martensitic (ODS-FM) steel to improve oxidation resistance at high temperature. By carrying out physical vapor deposition followed by inter-diffusion heat treatment, a thin Cr-rich carbide layer was produced on the ODS-FM steel. Both the as-received and surface-modified specimens were oxidation-tested at 650 °C in air and steam environments for 500 h. The surface-modified specimens showed improved oxidation resistance in both environments. In an air environment, both conditions exhibited a thin and continuous chromia layer, but the formation of Cr2O3 and (Mn, Cr)3O4 nodules resulted in greater weight gain for the as-received specimen. In a steam environment, weight gain increased for both the as-received and surface-modified specimen. Especially, the as-received specimen showed much greater weight gain with the formation of a thick oxide layer consisted of outer Fe-rich oxide and inner (Fe, Cr, Mn) oxide layers. On the other hand, a thin and continuous chromia layer was formed for the surface-modified specimen, which resulted in much less weight gain in a steam environment.
Power Side-Channel Attack Analysis: A Review of 20 Years of Study for the Layman
Authors: Randolph Mark , Diehl William
Published: May 2020

Physical cryptographic implementations are vulnerable to so-called side-channel attacks, in which sensitive information can be recovered by analyzing physical phenomena of a device during operation. In this survey, we trace the development of power side-channel analysis of cryptographic implementations over the last twenty years. We provide a foundation by exploring, in depth, several concepts, such as Simple Power Analysis (SPA), Differential Power Analysis (DPA), Template Attacks (TA), Correlation Power Analysis (CPA), Mutual Information Analysis (MIA), and Test Vector Leakage Assessment (TVLA), as well as the theories that underpin them. Our introduction, review, presentation, and survey of topics are provided for the “non expert”, and are ideal for new researchers entering this field. We conclude the work with a brief introduction to the use of test statistics (specifically Welch’s t-test and Pearson’s chi-squared test) as a measure of confidence that a device is leaking secrets through a side-channel and issue a challenge for further exploration.
Experimental and Theoretical Studies of Carboxylic Polymers with Low Molecular Weight as Inhibitors for Calcium Carbonate Scale
Authors: Zuo Yuwei , Yang Wenzhong , Zhang Kegui , Chen Yun , Yin Xiaoshuang , Liu Ying
Published: May 2020

Poly acrylic acid (PAA) and polyepoxysuccinic acid (PESA) were investigated as scale inhibitors. The static experiments certified that PAA was superior to PESA for the inhibition of calcium carbonate in the low molecular weight range. The X-ray diffraction patterns suggest that the effect of PAA on the calcite (1 0 4) and (1 1 0) crystal plane was more obvious. Scanning electron microscopy was used to study the surface morphology of the depositions, which indicated that the addition of scale inhibitors could disturb the normal growth of CaCO3 scale. The transmittance ratio of ferric oxide demonstrated that PAA had a better dispersion performance than PESA. The molecular dynamics simulation and quantum calculation were selected to theoretically explore the mechanism and structure of scale inhibitors, indicating that the interaction of PAA with (1 0 4) and (1 1 0) calcite crystal surfaces was stronger than PESA. In addition, the results indicated that the PAA with negative charge more easily adsorbed free Ca2+ in the aqueous phase. Based on these observations, PAA exhibited better scale inhibition and dispersion effects than PESA in the case of low molecular weight.
Reduced Sintering Temperatures of Li+ Conductive Li1.3Al0.3Ti1.7(PO4)3 Ceramics
Authors: Waetzig Katja , Heubner Christian , Kusnezoff Mihails
Published: May 2020

All-solid-state batteries (ASSB) are considered promising candidates for future energy storage and advanced electric mobility. When compared to conventional Li-ion batteries, the substitution of Li-ion conductive, flammable liquids by a solid electrolyte and the application of Li-metal anodes substantially increase safety and energy density. The solid electrolyte Li1.3Al0.3Ti1.7(PO4)3 (LATP) provides high Li-ion conductivity of about 10−3 S/cm and is considered a highly promising candidate for both the solid electrolyte-separator and the ionically conductive part of the all-solid state composite cathode, consisting of the cathode material, the solid electrolyte, and an electron conductor. Co-sintering of the composite cathode is a sophisticated challenge, because temperatures above 1000 °C are typically required to achieve the maximum ionic conductivity of LATP but provoke reactions with the cathode material, inhibiting proper electrochemical functioning in the ASSB. In the present study, the application of sintering aids with different melting points and their impact on the sinterability and the conductivity of LATP were investigated by means of optical dilatometry and impedance spectroscopy. The microstructure of the samples was analyzed by SEM. The results indicate that the sintering temperature can be reduced below 800 °C while maintaining high ionic conductivity of up to 3.6 × 10−4 S/cm. These insights can be considered a crucial step forward towards enable LATP-based composite cathodes for future ASSB.
Carbothermal Reduction Nitridation of Fly Ash, Diatomite and Raw Illite: Formation of Nitride Powders with Different Morphology and Photoluminescence Properties
Authors: Dou Kuizhou , Jiang Yinshan , Xue Bing , Wei Cundi , Li Fangfei
Published: May 2020

Rare-earth-doped SiAlON and Si3N4 materials from aluminosilicate starting materials have been reported to show superior photoluminescence (PL) properties. Three different starting materials, including pulverized coal furnace fly ash, diatomite and raw illite, were used for synthesis of nitride materials. The phase and morphology evolution of these products were carefully monitored at the low temperature range of 1350 °C to 1450 °C by X-ray diffraction (XRD), scanning electronic microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR). The PL properties of Eu-doped nitride products were also comparatively characterized. The results show that the type of starting material affects the phase composition and the photoluminescence properties of products. The existence of aluminum and alkali metals could effectively promote nitridation reactions. Aluminum in the starting materials led to the formation of different aluminum-rich nitride phases. Thus, β-SiAlON could be achieved at a much lower temperature (1350 °C) using raw illite or fly ash containing the proper amount of aluminum. Additionally, excess aluminum led to the formation of corundum and 15R-SiAlON. The products from pulverized coal furnace fly ash had more prismatic particles, and the products from diatomite had more fibrous particles. With the progress of the nitridation process, the fibers were increased, becoming longer and straighter, and the prismatic particles were more obvious. The presence of aluminum in the starting materials led to a blue shift in the photoluminescence spectrum.