bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of TIM-3 with BCLC Stage, Serum PD-L1 Detection, and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma
Authors: Tampaki Maria , Ionas Evangelos , Hadziyannis Emilia , Deutsch Melanie , Malagari Katerina , Koskinas John
Published: January 2020

Considering the increasing importance of immune checkpoints in tumor immunity we investigated the clinical relevance of serum T-cell immunoglobulin and mucin domain-3 (TIM-3) in patients with hepatocellular carcinoma (HCC). Serum TIM-3 levels were measured and their association with HCC stage and the detection of serum programmed death ligand-1 (PD-L1) were assessed. In patients submitted to transarterial chemoembolization (TACE), pre- and 1-week post-treatment TIM-3 levels were also evaluated. We studied 53 HCC patients with BCLC stages: 0 (5.7%), A (34%), B (32.1%), C (22.6%), and D (5.7%). The patients with advanced HCC (BCLC C) had significantly higher TIM-3 levels than patients with BCLC A (p = 0.009) and BCLC B (p = 0.019). TIM-3 levels were not associated with HCC etiology (p = 0.183). PD-L1 detection (9/53 patients) correlated with TIM-3 levels (univariate analysis, p = 0.047). In 33 patients who underwent TACE, post-treatment TIM-3 levels (231 pg/mL, 132–452) were significantly higher than pre-TACE levels (176 pg/mL, 110–379), (p = 0.036). Complete responders had higher post-TACE TIM-3 levels (534 pg/mL, 370–677) than partial responders (222 pg/mL, 131–368), (p = 0.028). Collectively, TIM-3 may have a role in anti-tumor immunity following TACE, setting a basis for combining immunotherapy and chemoembolization.
Heat Shock Protein 90 Chaperone Regulates the E3 Ubiquitin-Ligase Hakai Protein Stability
Authors: Díaz-Díaz Andrea , Roca-Lema Daniel , Casas-Pais Alba , Romay Gabriela , Colombo Giovanni , Concha Ángel , Graña Begoña , Figueroa Angélica
Published: January 2020

The E3 ubiquitin-ligase Hakai binds to several tyrosine-phosphorylated Src substrates, including the hallmark of the epithelial-to-mesenchymal transition E-cadherin, and signals for degradation of its specific targets. Hakai is highly expressed in several human cancers, including colon cancer, and is considered as a drug target for cancer therapy. Here, we report a link between Hakai and the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity. Hsp90 inhibitors specifically interfere with the association with its Hsp90 client proteins, and exhibit potent anti-cancer properties. By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Pharmacological inhibition of Hsp90 with geldanamycin results in the degradation of Hakai in a lysosome-dependent manner. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. We also show that geldanamycin suppresses cell motility at least in part through its action on Hakai expression. Taken together, our results identify Hakai as a novel Hsp90 client protein and shed light on the regulation of Hakai stability. Our results open the possibility to the potential use of Hsp90 inhibitors for colorectal cancer therapy through its action on Hakai client protein of Hsp90.
Cell Electropermeabilisation Enhancement by Non-Thermal-Plasma-Treated PBS
Authors: Chung Thai-Hoa , Stancampiano Augusto , Sklias Kyriakos , Gazeli Kristaq , André Franck , Dozias Sébastien , Douat Claire , Pouvesle Jean-Michel , Santos Sousa João , Robert Éric , Mir Lluis
Published: January 2020

The effectiveness of electrochemotherapy (ECT) in local eradication of tumours in human and veterinary medicine has been proven. ECT consists of increasing the uptake of cytotoxic drugs by means of pulsed electric fields (PEFs) that transiently permeabilise the cell membrane. Still, this tumour treatment includes some drawbacks that are linked to the characteristics of the intense electric pulses (EPs) used. Meanwhile, the emerging field of cancer therapies that are based on the application of non-thermal plasmas (NTP) has recently garnered interest because of their potentialities as rich sources of reactive species. In this work, we investigated the potential capabilities of the combined application of indirect NTP treatment and microsecond PEFs (µsPEFs) to outperform in vitro cell electropermeabilisation, the basis of ECT. Thus, phosphate-buffered saline (PBS) was plasma-treated (pPBS) and used afterwards to explore the effects of its combination with µsPEFs. Analysis of two different cell lines (DC-3F Chinese hamster lung fibroblasts and malignant B16-F10 murine melanoma cells), by flow cytometry, revealed that this combination resulted in significant increases of the level of cell membrane electropermeabilisation, even at very low electric field amplitude. The B16-F10 cells were more sensitive to the combined treatment than DC-3F cells. Importantly, the percentage of permeabilised cells reached values similar to those of cells exposed to classical electroporation field amplitude (1100 V/cm) when the cells were treated with pPBS before and after being exposed only to very low PEF amplitude (600 V/cm). Although the level of permeabilisation of the cells that are treated by the pPBS and the PEFs at 600 V/cm is lower than the level reached after the exposure to µsPEFs alone at 1100 V/cm, the combined treatment opens the possibility to reduce the amplitude of the EPs used in ECT, potentially allowing for a novel ECT with reduced side-effects.
Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers
Authors: Park Jee Soo , Pierorazio Phillip M. , Lee Ji Hyun , Lee Hyo Jung , Lim Young Soun , Jang Won Sik , Kim Jongchan , Lee Seung Hwan , Rha Koon Ho , Cho Nam Hoon , Ham Won Sik
Published: January 2020

The molecular characteristics of early-stage clear cell renal cell carcinomas (ccRCCs) measuring ≤7 cm associated with poor clinical outcomes remain poorly understood. Here, we sought to validate genes associated with ccRCC progression and identify candidate genes to predict ccRCC aggressiveness. From among 1069 nephrectomies performed on patients, RNA sequencing was performed for 12 ccRCC patients with aggressive characteristics and matched pairs of 12 ccRCC patients without aggressive characteristics. Using a prospective cohort (ClinicalTrials.gov Identifier: NCT03694912), the expression levels of nine genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, and BAIAP2L1) were measured by reverse-transcription polymerase chain reaction from frozen tissues, and their relation to Fuhrman grade was investigated in 70 patients with small ccRCC (≤4 cm). In total, 251 genes were differentially expressed and presented fold changes with p-values < 0.05; moreover, 10 genes with the greatest upregulation or downregulation in aggressive ccRCC remained significant even after adjustment. We validated previously identified genes that were associated with ccRCC progression and identified new candidate genes that reflected the aggressiveness of ccRCC. Our study provides new insight into the tumor biology of ccRCC and will help stratify patients with early-stage ccRCC by molecular subtyping.
MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer
Authors: Alday-Parejo Begoña , Richard François , Wörthmüller Janine , Rau Tilman , Galván José A. , Desmedt Christine , Santamaria-Martinez Albert , Rüegg Curzio
Published: January 2020

Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates with ESR1 and luminal genes GATA3 and FOXA1 expression and better prognosis, while low MAGI1 levels correlates with higher histological grade, more aggressive phenotype and worse prognosis. Experimentally, MAGI1 downregulation in the ER+ human BC cells MCF7 impairs ER expression and signaling, promotes cell proliferation, and reduces apoptosis and epithelial differentiation. MAGI1 downregulation in the ER+ murine BC cell line 67NR accelerates primary tumor growth and enhances experimental lung metastasis formation. MAGI1 expression is upregulated by estrogen/ER, downregulated by prostaglandin E2/COX-2axis, and negatively correlates with inflammation in ER+/HER2− BC patients. Taken together, we show that MAGI1 is a new potential tumor suppressor in ER+/HER2− breast cancer with possible prognostic value for the identification of patients at high-risk of relapse within this subset.
JNK Pathway Mediates Low Oxygen Level Induced Epithelial–Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer Cells
Authors: Tam Shing Yau , Wu Vincent W.C. , Law Helen K.W.
Published: January 2020

(1) Background: Epithelial–mesenchymal transition (EMT) and cancer cell stemness maintenance (SM) are important factors for cancer metastasis. Although hypoxia has been considered as a possible factor for EMT induction and promotion of SM, studies in this area, apart from hypoxia-inducible factor (HIF) pathways and severe hypoxia, are scant. This study aimed to evaluate the effects of different oxygen levels on EMT induction and SM and elucidate the signaling pathways involved in colorectal cancer cells. (2) Methods: Cell morphological analysis, migration assay, immunofluorescence staining of cytoskeleton and Western blotting were performed on human colorectal cancer cells HT-29, DLD-1, and SW-480 cultured at 1%, 10%, and normal (21%) O2 levels. The role played by c-Jun N-terminal kinase (JNK) was evaluated through the use of the specific JNK inhibitor SP600125. (3) Results: This study evaluated 1% and 10% O2 are possible conditions for EMT induction and SM. This study also demonstrated the partial relieve of EMT induction and SM by SP600125, showing the importance of the JNK pathway in these processes. Furthermore, this study proposed a novel pathway on the regulation of Akt by JNK-c-Jun. (4) Conclusions: This study suggests 10% O2 as another possible condition for EMT induction, and SM and JNK pathways play important roles in these processes through multiple factors. Inhibition of JNK could be explored as treatment for inhibiting metastasis in colorectal cancer cells.
Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision?
Authors: Noskova Hana , Kyr Michal , Pal Karol , Merta Tomas , Mudry Peter , Polaskova Kristyna , Ivkovic Tina Catela , Adamcova Sona , Hornakova Tekla , Jezova Marta , Kren Leos , Sterba Jaroslav , Slaby Ondrej
Published: January 2020

Background: Tumor mutational burden (TMB) is an emerging genomic biomarker in cancer that has been associated with improved response to immune checkpoint inhibitors (ICIs) in adult cancers. It was described that variability in TMB assessment is introduced by different laboratory techniques and various settings of bioinformatic pipelines. In pediatric oncology, no study has been published describing this variability so far. Methods: In our study, we performed whole exome sequencing (WES, both germline and somatic) and calculated TMB in 106 patients with high-risk/recurrent pediatric solid tumors of 28 distinct cancer types. Subsequently, we used WES data for TMB calculation using an in silico approach simulating two The Food and Drug Administration (FDA)-approved/authorized comprehensive genomic panels for cancer. Results: We describe a strong correlation between WES-based and panel-based TMBs; however, we show that this high correlation is significantly affected by inclusion of only a few hypermutated cases. In the series of nine cases, we determined TMB in two sequentially collected tumor tissue specimens and observed an increase in TMB along with tumor progression. Furthermore, we evaluated the extent to which potential ICI indication could be affected by variability in techniques and bioinformatic pipelines used for TMB assessment. We confirmed that this technological variability could significantly affect ICI indication in pediatric cancer patients; however, this significance decreases with the increasing cut-off values. Conclusions: For the first time in pediatric oncology, we assessed the reliability of TMB estimation across multiple pediatric cancer types using real-life WES and in silico analysis of two major targeted gene panels and confirmed a significant technological variability to be introduced by different laboratory techniques and various settings of bioinformatic pipelines.
Should Genetic Testing for Cancer Predisposition Be Standard-of-Care for Women with Invasive Breast Cancer? The Murtha Cancer Center Experience
Authors: Rummel Seth K. , Lovejoy Leann A. , Turner Clesson E. , Shriver Craig D. , Ellsworth Rachel E.
Published: January 2020

Currently, genetic testing is offered only to women diagnosed with breast cancer who meet a defined set of criteria and is not included as standard-of-care treatment at the time of diagnosis. Thus, a significant number of women diagnosed with breast cancer may miss the opportunity for precision medical treatment and risk management. The effects of eligibility, timing, and uptake of genetic testing were evaluated in a cohort of women with invasive breast cancer diagnosed between 2001–2018. Risk status was estimated using NCCN BRCA1/2 testing criteria and panel testing was performed for all women who had genomic DNA available. Of the 1231 women, 57.8% were eligible for genetic testing. Uptake of testing within high-risk women was 42.7% of which 6.6% pursued clinical testing only after a second tumor event. Mutation frequencies were 15.8%, 5.5%, and 4.0% in high-risk women with clinical testing, high-risk women without clinical testing, and low-risk women, respectively. More than 4% of all patients harbored pathogenic or likely pathogenic mutations detected only in the research setting. Inclusion of panel testing at the time of diagnosis would allow for appropriate surveillance and treatment strategies to be employed to reduce the risk of secondary tumors and improve patient outcome.
Characteristic and Catalytic Performance of Co and Co-Mo Metal Impregnated in Sarulla Natural Zeolite Catalyst for Hydrocracking of MEFA Rubber Seed Oil into Biogasoline Fraction
Authors: Sihombing Junifa Layla , Gea Saharman , Wirjosentono Basuki , Agusnar Harry , Pulungan Ahmad Nasir , Herlinawati Herlinawati , Yusuf Muhammad , Hutapea Yasir Arafat
Published: January 2020

This research was aimed to investigate the effect of Co and Co-Mo metal loaded on Sarulla Natural Zeolite which has been activated and calcined (SNZ-Cal) as supports for better understanding of characterization and catalytic activity on hydrocracking of MEFA rubber seed oil. The Co and Co-Mo metal was added through a wet impregnation method using Co(NO3)2·6H2O and (NH4)·6Mo7O24·4H2O precursor salts. The catalyst was oxidized at 500 °C for 2 h within oxygen gas flow, followed by a reduction process with H2 gas flow with similar condition to obtain the catalysts. Based on the result, it was found that the resulted catalysts displayed an increase in crystal grain size compared to the metal-free catalyst. Particularly, catalyst that was impregnated with Co metal has a larger surface area and pore diameter and smaller pore volume than Co-Mo metal impregnated to the catalyst. In fact, it was revealed that this catalyst possessed the highest catalytic activity and selectivity. Furthermore, the resulting gas products reached 64 wt.% and the distribution of biogasoline fraction of hydrocarbons (C6-C12) amounted to 83.19 wt.%.
Determining the Location of Co2+ in Zeolites by UV-Vis Diffuse Reflection Spectroscopy: A Critical View
Authors: Bellmann Andrea , Rautenberg Christine , Bentrup Ursula , Brückner Angelika
Published: January 2020

UV–Vis spectroscopy as well as in situ FTIR spectroscopy of pyridine and CO adsorption were applied to determine the nature of Co species in microporous, mesoporous, and mixed oxide materials like Co–ZSM-5, Co/Na–ZSM-5, Co/Al–SBA-15, and Co/Al2O3–SiO2. Because all sample types show comparable UV–Vis spectra with a characteristic band triplet, the former described UV–Vis band deconvolution method for determination and quantification of individual cationic sites in the zeolite appears doubtful. This is also confirmed by results of pyridine and CO adsorption revealing that all Co–zeolite samples contain two types of Co2+ species located at exchange positions as well as in oxide-like clusters independent of the Co content, while in Co/Al–SBA-15 and Co/Al2O3–SiO2 only Co2+ species in oxide-like clusters occur. Consequently, the measured UV–Vis spectra represent not exclusively isolated Co2+ species, and the characteristic triplet band is not only related to γ-, β-, and α-type Co2+ sites in the zeolite but also to those dispersed on the surface of different oxide supports. The study demonstrates that for proper characterization of the formed Co species, the use of complementary methods is required.
Acknowledgement to Reviewers of Catalysts in 2019
Authors:   Editorial Office
Published: January 2020

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...]
ETV6/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia
Authors: Montaño Adrián , Ordoñez Jose Luis , Alonso-Pérez Verónica , Hernández-Sánchez Jesús , Santos Sandra , González Teresa , Benito Rocío , García-Tuñón Ignacio , Hernández-Rivas Jesús María
Published: January 2020

Background: The t(12;21)(p13;q22), which fuses ETV6 and RUNX1 genes, is the most common genetic abnormality in children with B-cell precursor acute lymphoblastic leukaemia. The implication of the fusion protein in leukemogenesis seems to be clear. However, its role in the maintenance of the disease continues to be controversial. Methods: Generation of an in vitro ETV6/RUNX1 knock out model using the CRISPR/Cas9 gene editing system. Functional characterization by RNA sequencing, proliferation assays, apoptosis and pharmacologic studies, and generation of edited-cell xenograft model. Results: The expression of ETV6/RUNX1 fusion gene was completely eliminated, thus generating a powerful model on which to study the role of the fusion gene in leukemic cells. The loss of fusion gene expression led to the deregulation of biological processes affecting survival such as apoptosis resistance and cell proliferation capacity. Tumour cells showed higher levels of apoptosis, lower proliferation rate and a greater sensitivity to PI3K inhibitors in vitro along as a decrease in tumour growth in xenografts models after ETV6/RUNX1 fusion gene abrogation. Conclusions: ETV6/RUNX1 fusion protein seems to play an important role in the maintenance of the leukemic phenotype and could thus become a potential therapeutic target.
Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin
Authors: Zheng Mingzhe , Ambesi Anthony , J. McKeown-Longo Paula
Published: January 2020

Chronic inflammation and subsequent tissue fibrosis are associated with a biochemical and mechanical remodeling of the fibronectin matrix. Due to its conformational lability, fibronectin is considerably stretched by the contractile forces of the fibrotic microenvironment, resulting in the unfolding of its Type III domains. In earlier studies, we have shown that a peptide mimetic of a partially unfolded fibronectin Type III domain, FnIII-1c, functions as a Damage Associated Molecular Pattern (DAMP) molecule to induce activation of a toll-like receptor 4 (TLR4)/NF-κB pathway and the subsequent release of fibro-inflammatory cytokines from human dermal fibroblasts. In the current study, we evaluated the requirement of the canonical TLR4/MD2/CD14 receptor complex in the regulation of FnIII-1c induced cytokine release. Using dermal fibroblasts and human embryonic kidney (HEK) cells, we found that all the components of the TLR4/MD2/CD14 complex were required for the release of the fibro-inflammatory cytokine, interleukin 8 (IL-8) in response to both FnIII-1c and the canonical TLR4 ligand, lipopolysaccharide (LPS). However, FnIII-1c mediated IL-8 release was strictly dependent on membrane-associated CD14, while LPS could use soluble CD14. These findings demonstrate that LPS and FnIII-1c share a similar but not identical mechanism of TLR4 activation in human dermal fibroblasts.
miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment
Authors: Conti Ilaria , Varano Gabriele , Simioni Carolina , Laface Ilaria , Milani Daniela , Rimondi Erika , Neri Luca M.
Published: January 2020

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.
Extracellular Vesicles for Cancer Therapy: Impact of Host Immune Response
Authors: Gilligan Katie E. , Dwyer Róisín M.
Published: January 2020

In recent times, extracellular vesicles (EVs) have come under the spotlight as potential therapeutics for cancer, due to the relative ease of manipulation of contents and potential for tumor targeting. The use of EVs as delivery vehicles may bypass some of the negative effects associated with cell-based carriers, and there has been a major focus on defining EV subtypes, establishing transparent nomenclature, and isolation and characterization techniques. EVs are believed to be a fingerprint of the secreting cell and so researchers harness the positive aspects of a particular cell of origin, and can then further modify EV contents to improve therapeutic efficacy. In this review, we highlight studies employing EVs as cancer therapeutics that have reported on immune response. As we rapidly advance towards potential application in the clinical setting, the question of immune response to EV administration in the cancer setting has become critically important.
Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor
Authors: Amrutkar Manoj , Larsen Emma Kristine , Aasrum Monica , Finstadsveen Anette Vefferstad , Andresen Per Arne , Verbeke Caroline S. , Gladhaug Ivar P.
Published: January 2020

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, and its treatment remains a challenge. As the existing in vitro experimental models offer only a limited resemblance to human PDAC, there is a strong need for additional research tools to better understand PDAC tumor biology, particularly the impact of the tumor stroma. Here, we report for the first time the establishment and characterization of human PDAC-derived paired primary monolayer cultures of (epithelial) cancer cells (PCCs) and mesenchymal stellate cells (PSCs) derived from the same tumor by the outgrowth method. Characterization of cell morphology, cytostructural, and functional profiles and proteomics-based secretome analysis were performed. All PCCs harbored KRAS and TP53 mutations, and expressed cytokeratin 19, ki-67, and p53, while the expression of EpCAM and vimentin was variable. All PSCs expressed α-smooth muscle actin (α-SMA) and vimentin. PCCs showed a significantly higher growth rate and proliferation than PSCs. Secretome analysis confirmed the distinct nature of PCCs as compared to PSCs and allowed identification of potential molecular regulators of PSC-conditioned medium (PSC-CM)-induced migration of PCCs. Paired primary cultures of PCCs and PSCs derived from the same tumor specimen represent a novel experimental model for basic research in PDAC tumor biology.
Dysregulated Interorganellar Crosstalk of Mitochondria in the Pathogenesis of Parkinson’s Disease
Authors: Sironi Lara , Restelli Lisa Michelle , Tolnay Markus , Neutzner Albert , Frank Stephan
Published: January 2020

The pathogenesis of Parkinson’s disease (PD), the second most common neurodegenerative disorder, is complex and involves the impairment of crucial intracellular physiological processes. Importantly, in addition to abnormal α-synuclein aggregation, the dysfunction of various mitochondria-dependent processes has been prominently implicated in PD pathogenesis. Besides the long-known loss of the organelles’ bioenergetics function resulting in diminished ATP synthesis, more recent studies in the field have increasingly focused on compromised mitochondrial quality control as well as impaired biochemical processes specifically localized to ER–mitochondria interfaces (such as lipid biosynthesis and calcium homeostasis). In this review, we will discuss how dysregulated mitochondrial crosstalk with other organelles contributes to PD pathogenesis.
Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells
Authors: Lee Jae Hyuk , Subedi Lalita , Kim Sun Yeou
Published: January 2020

Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as N-acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.
Acknowledgement to Reviewers of Chemistry in 2019
Authors:   Chemistry Editorial Office
Published: January 2020

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...]
Sensitivity Analysis of Rotor/Stator Interactions Accounting for Wear and Thermal Effects within Low- and High-Pressure Compressor Stages
Authors: Nyssen Florence , Batailly Alain
Published: January 2020

In the current design of turbomachines, engine performance is improved by reducing the clearances between the rotating components and the stator, which allows for loss decrease. Due to these clearance reductions, contact events may occur between the rotor and the stator. An abradable coating is deposited along the stator circumference as a sacrificial material to lower the contact severity. However, experiments highlighted the occurrence of rotor/stator interactions with high wear depth on the abradable coating as well as high temperature increases within the abradable coating following contacts. This work focuses on the sensitivity analysis of rotor/stator interactions with respect to the rotor angular speed and the initial clearances between the rotor and the stator, taking into account thermal effects within the abradable coating. Convergence analyses are first conducted to validate the numerical model. Then, after a calibration of the thermal model of the abradable coating based on two experimental test cases, the numerical model is used to investigate the cross effects of the angular speed and the initial clearances on the obtained rotor/stator interactions.
Effects of Process Parameters on Geometrical Characteristics, Microstructure and Tribological Properties of TiB2 Reinforced Inconel 718 Alloy Composite Coatings by Laser Cladding
Authors: Tang Binghui , Tan Yefa , Zhang Zhongwei , Xu Ting , Sun Zhidan , Li Xiaotun
Published: January 2020

The TiB2 reinforced Inconel 718 alloy composite coatings were prepared on carbon steel by laser cladding. The energy input (the ratio of laser power and scanning speed, E) was introduced to investigate the effects of process parameters on geometrical characteristics, microstructure and tribological properties of composite coatings. The results show that the dilution rate decreases and the contact angle increases, respectively, as E decreases from 200.00 J/mm to 80.00 J/mm, which causes the decrease of the boding strength from 1.91 GPa to 0.39 GPa. The composite coatings contain the phases of γ-(Ni, Fe), Laves, TiB2, TiB, TiC, Ni3B, CrB4 and Cr23C6. As E decreases from 200.00 J/mm to 133.33 J/mm, the primary dendrite arm spacing (PDAS) and the Laves content of the composite coating decrease for the increase of cooling rate, leading to the increase of microhardness, the improvement of tribological properties and the change of wear mechanism from the severe multi-plastic deformation wear, adhesive wear and oxidative wear to the slight abrasive wear. However, as E decreases from 133.33 J/mm to 80.00 J/mm, for the weak Marangoni convection, TiB2 particles are prone to aggregate in the top of the composite coating which causes the increase of the PDAS and the Laves content, leading to the decrease of the microhardness and the degradation of tribological properties, and the wear mechanism change to the multi-plastic deformation wear and abrasive wear gradually.
Surface Properties of Beech Wood after CO2 Laser Engraving
Authors: Kúdela Jozef , Kubovský Ivan , Andrejko Michal
Published: January 2020

The paper deals with the properties of a beech wood surface treated by CO2 laser engraving. The studied concerns were the discoloration, changes to morphology assessed through roughness and waviness parameters, and surface wetting with standard liquids (water and diiodomethane), with the aim of determining the wood surface free energy. The results have confirmed that the studied properties of the beech wood surface varied significantly, which were affected by the laser beam power P and raster density n. With increasing P and n, the lightness L* (expressed in CIE L*a*b* color space) decreased significantly. We also observed significant variation in the color coordinates a* and b*. At 8% laser power, the roughness and waviness parameters measured parallel as well as perpendicular to the grain increased proportionally with the increasing raster density. However, 4% laser power was not associated with distinct changes. Increasing the raster density reduced beech wood surface wetting equally with water and with diiodomethane. This was reflected in the higher contact angle values. The wood surface exhibited higher hydrophobicity at 4% laser power. At this power, the increasing raster density was reflected in the decreasing surface free energy, due to its polar component decrease. At 8% laser power, the changes in surface free energy were very minor from the practical viewpoint. The results suggest a potential good adhesion between film-forming materials and wood. However, the gluing performance may be negatively affected by the high roughness attained at 8% laser power and at higher raster densities.
Dynamic Boundary of P-Set and Intelligent Acquisition for Two Types of Information Fusion
Authors: Li Shouwei , Xiao Yao , Shi Kaiquan
Published: January 2020

The development of information technology brings the challenge of data redundancy and data shortage to information fusion. Based on the dynamic boundary characteristics of p-set, this paper analyzes the structure and generation of p-augmented matrix, and then analyzes the dynamic generation of information equivalence class, and then proposes an intelligent acquisition algorithm of information equivalence class based on matrix reasoning. In addition, this paper analyzes two types of information fusion, namely information redundancy fusion and information supplement fusion. Then, the relationship among redundant information fusion, supplementary information fusion, and information equivalence classes is analyzed. Finally, this paper presents the application of intelligent acquisition of information equivalence class in information retrieval.
Stability and Phase Transitions of Nontoxic γ-Cyclodextrin-K+ Metal-Organic Framework in Various Solvents
Authors: Krūkle-Bērziņa Kristīne , Belyakov Sergey , Mishnev Anatoly , Shubin Kirill
Published: January 2020

Cyclodextrin (CD) has been used to prepare biocompatible and nontoxic metal-organic frameworks (MOFs) suitable for biomedical applications as drug carriers. In this study, γ-CD/K-based MOF (γ-CD-MOF-1-α) was synthesized and its stability in various solvents was explored by single-crystal X-ray diffractometry (SCXRD) and powder X-ray diffractometry (PXRD). As a result of solvent-induced phase transformations, two novel crystalline phases of γ-CD-MOF-1 were discovered. The newly formed ε- and δ-phases crystallize in orthorhombic and tetragonal symmetry, respectively. In ε-phase, toluene was determined as a guest molecule by SCXRD. Interactions between γ-cyclodextrin and solvent molecules in ε-phase were evaluated using Hirshfeld surface analysis. The thermal stability of the new crystal forms of γ-CD-MOF-1 was analyzed by differential scanning calorimetry and thermogravimetric analysis.
Raman Scattering: From Structural Biology to Medical Applications
Authors: Vlasov Alexey V. , Maliar Nina L. , Bazhenov Sergey V. , Nikelshparg Evelina I. , Brazhe Nadezda A. , Vlasova Anastasiia D. , Osipov Stepan D. , Sudarev Vsevolod V. , Ryzhykau Yury L. , Bogorodskiy Andrey O. , Zinovev Egor V. , Rogachev Andrey V. , Manukhov Ilya V. , Borshchevskiy Valentin I. , Kuklin Alexander I. , Pokorný Jan , Sosnovtseva Olga , Maksimov Georgy V. , Gordeliy Valentin I.
Published: January 2020

This is a review of relevant Raman spectroscopy (RS) techniques and their use in structural biology, biophysics, cells, and tissues imaging towards development of various medical diagnostic tools, drug design, and other medical applications. Classical and contemporary structural studies of different water-soluble and membrane proteins, DNA, RNA, and their interactions and behavior in different systems were analyzed in terms of applicability of RS techniques and their complementarity to other corresponding methods. We show that RS is a powerful method that links the fundamental structural biology and its medical applications in cancer, cardiovascular, neurodegenerative, atherosclerotic, and other diseases. In particular, the key roles of RS in modern technologies of structure-based drug design are the detection and imaging of membrane protein microcrystals with the help of coherent anti-Stokes Raman scattering (CARS), which would help to further the development of protein structural crystallography and would result in a number of novel high-resolution structures of membrane proteins—drug targets; and, structural studies of photoactive membrane proteins (rhodopsins, photoreceptors, etc.) for the development of new optogenetic tools. Physical background and biomedical applications of spontaneous, stimulated, resonant, and surface- and tip-enhanced RS are also discussed. All of these techniques have been extensively developed during recent several decades. A number of interesting applications of CARS, resonant, and surface-enhanced Raman spectroscopy methods are also discussed.
In Situ TEM Crystallization of Amorphous Iron Particles
Authors: Falqui Andrea , Loche Danilo , Casu Alberto
Published: January 2020

Even though sub-micron and nano-sized iron particles generally display single or polycrystalline structures, a growing interest has also been dedicated to the class of amorphous ones, whose absence of a crystal structure is capable of modifying their physical properties. Among the several routes so far described to prepare amorphous iron particles, we report here about the crystallization of those prepared by chemical reduction of Fe3+ ions using NaBH4, with sizes ranging between 80 and 200 nm and showing a high stability against oxidation. Their crystallization was investigated by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in situ heating transmission electron microscopy (TEM). The latter technique was performed by the combined use of electron diffraction of a selected sample area, and bright and dark field TEM imaging, and allowed determining that the crystallization turns the starting amorphous particles into polycrystalline α-Fe ones. Also, under the high vacuum of the TEM column, the crystallization temperature of the particles shifted to 550 °C from the 465 °C, previously observed by DSC and XRD under 105 Pa of Ar. This indicates the pivotal role of the external pressure in influencing the starting point of phase transition. Conversely, upon both the DSC/XRD pressure and the TEM vacuum conditions, the mean size of the crystal domains increases as a consequence of further thermal increase, even if with some pressure-related differences.
Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data
Authors: Al Rahal Okba , Majumder Mridul , Spillman Mark J. , van de Streek Jacco , Shankland Kenneth
Published: January 2020

Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement.
Interplay between Convective and Viscoelastic Forces Controls the Morphology of In Vitro Paclitaxel-Stabilized Microtubules
Authors: Barnes Eftihia , Guan Xin , Alberts Erik M. , Thornell Travis L. , Warner Christopher M. , Pilkiewicz Kevin R.
Published: January 2020

Microtubules (MTs) are self-assembling, high-aspect-ratio tubular nanostructures formed from the polymerization of tubulin protein. MTs are capable of globally assembling into optically birefringent morphologies, but there is disagreement on the mechanisms driving this behavior. We investigated the temporal evolution of paclitaxel (PTX)-stabilized MT solutions under a range of in vitro conditions. Significant morphological differences were observed in the polymerized PTX-MT solutions as a consequence of varying the orientation of the reaction vessel (vertical vs. horizontal), the type of heating source (hot plate vs. incubator), the incubation time, and the concentration of PTX (high vs. low). The most robust birefringent patterns were found only in vertically oriented cuvettes that were heated asymmetrically on a hot plate, suggesting dependence upon a convective flow, which we confirmed with a combination of optical and thermal imaging. Higher concentrations of PTX led to denser PTX-MT domain formation and brighter birefringence, due to more complete polymerization. Combining our experimental observations, we conclude that birefringent patterns arise principally through a combination of convective and viscoelastic forces, and we identify the sequence of dynamical stages through which they evolve.
Physical Science Teacher Skills in a Conceptual Explanation
Authors: Geelan David
Published: January 2020

There is a long history of philosophical inquiry into the concept of explanation in science, and this work has some implications for the ways in which science teachers, particularly in the physical sciences (physics and chemistry), explain ideas to students. Recent work has outlined a constructivist approach to developing, delivering, and refining explanations focused on enhancing student’s understanding of the powerful concepts of science. This paper reviews the history of concepts of explanation in science and in science teaching, and reports research findings that describe some ways in which science teachers have been observed to explain ideas in Year 11 Physics classrooms in Australia and Canada.
Computer Vision Intelligent Approaches to Extract Human Pose and Its Activity from Image Sequences
Authors: Gonçalves Paulo J. S. , Lourenço Bernardo , Santos Samuel , Barlogis Rodolphe , Misson Alexandre
Published: January 2020

The purpose of this work is to develop computational intelligence models based on neural networks (NN), fuzzy models (FM), support vector machines (SVM) and long short-term memory networks (LSTM) to predict human pose and activity from image sequences, based on computer vision approaches to gather the required features. To obtain the human pose semantics (output classes), based on a set of 3D points that describe the human body model (the input variables of the predictive model), prediction models were obtained from the acquired data, for example, video images. In the same way, to predict the semantics of the atomic activities that compose an activity, based again in the human body model extracted at each video frame, prediction models were learned using LSTM networks. In both cases the best learned models were implemented in an application to test the systems. The SVM model obtained 95.97% of correct classification of the six different human poses tackled in this work, during tests in different situations from the training phase. The implemented LSTM learned model achieved an overall accuracy of 88%, during tests in different situations from the training phase. These results demonstrate the validity of both approaches to predict human pose and activity from image sequences. Moreover, the system is capable of obtaining the atomic activities and quantifying the time interval in which each activity takes place.
Extended Spatial-Index LED Modulation for Optical MIMO-OFDM Wireless Communication
Authors: S. Hussein Hany , Hagag Mohamed , Farrag Mohammed
Published: January 2020

An efficient optical modulation technique for multi-input multi-output (MIMO) orthogonal frequency division multiplexing (OFDM) visible light communication system is proposed in this paper. The proposed modulation technique is termed as extended spatial-index light-emitting diode (LED) modulation. In the proposed technique, the indices (the spatial domain) of the LEDs are exploited in a dynamic style to not only get rid of the optical OFDM time-domain ( OFDM t d ) shaping problem but also to expand the LED indices spatial modulation domain. The indices of the active LEDs in the proposed technique are changed from the two LEDs active situation to the situation where all or several LEDs are active. Moreover, within the selected active LED indices, the power weight distribution and the positions of the OFDM components are varied to expand the resultant spatial domain. Therefore, the proposed technique offers a considerable spectral efficiency improvement over the up-to-date LED index OFDM modulation schemes even with a lower number of LEDs. The key idea of the proposed technique is to maximize the LEDs’ indices spatial position (spatial domain) utilization, where both the power weight allocation and the positions of the complex OFDM time domain components are varying several times over the same active LED indices combination, which improve the optical system spectral efficiency. The simulation results asserted the superiority of the proposed technique, as it improves both the average bit error rate (ABER) and the achievable data rate (R) compared with existing up-to-date OFDM-LED index modulations with even lower computational complexity.
Motor Imagery Based Continuous Teleoperation Robot Control with Tactile Feedback
Authors: Xu Baoguo , Li Wenlong , He Xiaohang , Wei Zhiwei , Zhang Dalin , Wu Changcheng , Song Aiguo
Published: January 2020

Brain computer interface (BCI) adopts human brain signals to control external devices directly without using normal neural pathway. Recent study has explored many applications, such as controlling a teleoperation robot by electroencephalography (EEG) signals. However, utilizing the motor imagery EEG-based BCI to perform teleoperation for reach and grasp task still has many difficulties, especially in continuous multidimensional control of robot and tactile feedback. In this research, a motor imagery EEG-based continuous teleoperation robot control system with tactile feedback was proposed. Firstly, mental imagination of different hand movements was translated into continuous command to control the remote robotic arm to reach the hover area of the target through a wireless local area network (LAN). Then, the robotic arm automatically completed the task of grasping the target. Meanwhile, the tactile information of remote robotic gripper was detected and converted to the feedback command. Finally, the vibrotactile stimulus was supplied to users to improve their telepresence. Experimental results demonstrate the feasibility of using the motor imagery EEG acquired by wireless portable equipment to realize the continuous teleoperation robot control system to finish the reach and grasp task. The average two-dimensional continuous control success rates for online Task 1 and Task 2 of the six subjects were 78.0% ± 6.1% and 66.2% ± 6.0%, respectively. Furthermore, compared with the traditional EEG triggered robot control using the predefined trajectory, the continuous fully two-dimensional control can not only improve the teleoperation robot system’s efficiency but also give the subject a more natural control which is critical to human–machine interaction (HMI). In addition, vibrotactile stimulus can improve the operator’s telepresence and task performance.