bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy
Authors: Scioli Maria Giovanna , Storti Gabriele , D’Amico Federico , Gentile Pietro , Fabbri Giulia , Cervelli Valerio , Orlandi Augusto
Published: July 2019

Breast cancer is the most common form of tumor in women and the leading cause of cancer-related mortality. Even though the major cellular burden in breast cancer is constituted by the so-called bulk tumor cells, another cell subpopulation named cancer stem cells (CSCs) has been identified. The latter have stem features, a self-renewal capacity, and the ability to regenerate the bulk tumor cells. CSCs have been described in several cancer types but breast cancer stem cells (BCSCs) were among the first to be identified and characterized. Therefore, many efforts have been put into the phenotypic characterization of BCSCs and the study of their potential as prognostic indicators and therapeutic targets. Many dysregulated pathways in BCSCs are involved in the epithelial–mesenchymal transition (EMT) and are found up-regulated in circulating tumor cells (CTCs), another important cancer cell subpopulation, that shed into the vasculature and disseminate along the body to give metastases. Conventional therapies fail at eliminating BCSCs because of their quiescent state that gives them therapy resistance. Based on this evidence, preclinical studies and clinical trials have tried to establish novel therapeutic regimens aiming to eradicate BCSCs. Markers useful for BCSC identification could also be possible therapeutic methods against BCSCs. New approaches in drug delivery combined with gene targeting, immunomodulatory, and cell-based therapies could be promising tools for developing effective CSC-targeted drugs against breast cancer.
Platelets as Key Factors in Hepatocellular Carcinoma
Authors: Pavlovic Natasa , Rani Bhavna , Gerwins Pär , Heindryckx Femke
Published: July 2019

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic inflammation and liver damage. The hepatic microenvironment plays a crucial role in the disease development, as players such as hepatic stellate cells, resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix, and a variety of immune cells interact in highly complex and intertwined signaling pathways. A key factor in these cross-talks are platelets, whose role in cancer has gained growing evidence in recent years. Platelets have been reported to promote HCC cell proliferation and invasion, but their involvement goes beyond the direct effect on tumor cells, as they are known to play a role in pro-fibrinogenic signaling and the hepatic immune response, as well as in mediating interactions between these factors in the stroma. Anti-platelet therapy has been shown to ameliorate liver injury and improve the disease outcome. However, platelets have also been shown to play a crucial role in liver regeneration after organ damage. Therefore, the timing and microenvironmental setting need to be kept in mind when assessing the potential effect and therapeutic value of platelets in the disease progression, while further studies are needed for understanding the role of platelets in patients with HCC.
Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile
Authors: Dubbelboer Ilse R. , Pavlovic Natasa , Heindryckx Femke , Sjögren Erik , Lennernäs Hans
Published: July 2019

Hepatocellular carcinoma is often treated with a combination of doxorubicin and embolization, exposing it to high concentrations and hypoxia. Separation of the possible synergistic effect of this combination in vivo is difficult. Here, treatment with doxorubicin, under hypoxia or normoxia in different liver cancer cell lines, was evaluated. Liver cancer cells HepG2, Huh7, and SNU449 were exposed to doxorubicin, hypoxia, or doxorubicin + hypoxia with different duration. Treatment response was evaluated with cell viability, apoptosis, oxidative stress, and summarized with IC50. The protein profile of a 92-biomarker panel was analyzed on cells treated with 0 or 0.1 µM doxorubicin during 6 or 72 h, under normoxia or hypoxia. Hypoxia decreased viability of HepG2 and SNU499. HepG2 was least and SNU449 most tolerant to doxorubicin treatment. Cytotoxicity of doxorubicin increased over time in HepG2 and Huh7. The combination of doxorubicin + hypoxia affected the cells differently. Normalized protein expression was lower for HepG2 than Huh7 and SNU449. Hierarchical clustering separated HepG2 from Huh7 and SNU449. These three commonly used cell lines have critically different responses to chemotherapy and hypoxia, which was reflected in their different protein expression profile. These different responses suggest that tumors can respond differently to the combination of local chemotherapy and embolization.
The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer
Authors: Rodriguez David , Ramkairsingh Marc , Lin Xiaozeng , Kapoor Anil , Major Pierre , Tang Damu
Published: July 2019

Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance.
CD56 Homodimerization and Participation in Anti-Tumor Immune Effector Cell Functioning: A Role for Interleukin-15
Authors: Van Acker Heleen H. , Van Acker Zoë P. , Versteven Maarten , Ponsaerts Peter , Pende Daniela , Berneman Zwi N. , Anguille Sébastien , Van Tendeloo Viggo F. , Smits Evelien L.
Published: July 2019

A particularly interesting marker to identify anti-tumor immune cells is the neural cell adhesion molecule (NCAM), also known as cluster of differentiation (CD)56. Namely, hematopoietic expression of CD56 seems to be confined to powerful effector immune cells. Here, we sought to elucidate its role on various killer immune cells. First, we identified the high motility NCAM-120 molecule to be the main isoform expressed by immune cells. Next, through neutralization of surface CD56, we were able to (1) demonstrate the direct involvement of CD56 in tumor cell lysis exerted by CD56-expressing killer cells, such as natural killer cells, gamma delta (γδ) T cells, and interleukin (IL)-15-cultured dendritic cells (DCs), and (2) reveal a putative crosstalk mechanism between IL-15 DCs and CD8 T cells, suggesting CD56 as a co-stimulatory molecule in their cell-to-cell contact. Moreover, by means of a proximity ligation assay, we visualized the CD56 homophilic interaction among cancer cells and between immune cells and cancer cells. Finally, by blocking the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase (PI3K)–Akt pathway, we showed that IL-15 stimulation directly led to CD56 upregulation. In conclusion, these results underscore the previously neglected importance of CD56 expression on immune cells, benefiting current and future immune therapeutic options.
GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
Authors: Le Guin Claudia Helga Dorothee , Metz Klaus Alfred , Kreis Stefan Horst , Bechrakis Nikolaos Emmanouel , Bornfeld Norbert , Zeschnigk Michael , Lohmann Dietmar Rudolf
Published: July 2019

Several tumors, including uveal melanoma, show somatic mutations of GNAQ/GNA11. Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melanoma and circumscribed choroidal hemangioma. Here, we report the results of GNAQ/GNA11 mutation analysis in samples from circumscribed choroidal hemangioma. Deep amplicon sequencing (Illumina MiSeq, San Diego, CA, USA) of positions R183 and Q209 of GNAQ and GNA11 in tissue samples from 33 patients with histologically diagnosed circumscribed choroidal hemangioma. All patients underwent biopsy or enucleation at our clinic between 2008 and 2018. To enable detection of variant alleles at low fractions, read depth exceeded 15,000-fold. DNA for genetic analysis was prepared from either snap-frozen (n = 22) or FFPE (n = 11) tissue samples. Samples from 28/33 patients (85%) showed a somatic missense mutation of GNAQ (c.626 A > G) predicted to result in p.Q209R. Variant allele fraction was variable (range 2.3% to 28%). Variants of GNAQ resulting in p.Q209 are characteristic for circumscribed choroidal hemangiomas. It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R. Moreover, the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.Q209R are very rare.
So Close, yet so Far: Discrepancies between Uveal and Other Melanomas. A Position Paper from UM Cure 2020
Authors: Rodrigues Manuel , de Koning Leanne , Coupland Sarah , Jochemsen Aart , Marais Richard , Stern Marc-Henri , Valente André , Barnhill Raymond , Cassoux Nathalie , Evans Andrew , Galloway Iain , Jager Martine , Kapiteijn Ellen , Romanowska-Dixon Bozena , Ryll Bettina , Roman-Roman Sergio , Piperno-Neumann Sophie ,   the UM Cure 2020 Consortium
Published: July 2019

Despite much progress in our understanding of uveal melanoma (UM) over the past decades, this rare tumour is still often misclassified. Although UM, like other melanomas, is very probably derived from melanocytes, it is drastically different from cutaneous melanoma and most other melanoma subtypes in terms of epidemiology, aetiology, biology and clinical features, including an intriguing metastatic hepatotropism. UM carries distinctive prognostic chromosome alterations, somatic mutations and gene expression profiles, allowing an active tailored surveillance strategy and dedicated adjuvant clinical trials. There is no standard systemic treatment for disseminated UM at present. In contrast to cutaneous melanoma, UMs are not BRAF-mutated, thus curtailing the use of B-Raf inhibitors. Although these tumours are characterised by some immune infiltrates, immune checkpoint inhibitors are rarely effective, possibly due to a low mutation burden. UM patients across the world not only face rare cancer-related issues (e.g., specific management strategies, access to information and to expert centres), but also specific UM problems, which can be exacerbated by the common misconception that it is a subtype of cutaneous melanoma. As a European Consortium dedicated to research on UM and awareness on the disease, “UM Cure 2020” participants urge medical oncologists, pharmaceutical companies, and regulatory agencies to acknowledge UM as a melanoma with specific issues, in order to accelerate the development of new therapies for patients.
Independent Negative Prognostic Role of TCF1 Expression within the Wnt/β-Catenin Signaling Pathway in Primary Breast Cancer Patients
Authors: Saponaro Concetta , Scarpi Emanuela , Zito Francesco Alfredo , Giotta Francesco , Silvestris Nicola , Mangia Anita
Published: July 2019

The Wnt pathway is involved in the progression of breast cancer (BC). We aimed to evaluate the expression of some components of the Wnt pathway (β-catenin, FZD4 (frizzled receptor 4), LRP5 (low-density lipoprotein receptor-related protein 5), LRP6, and TCF1 (T-cell factor 1)) to detect potential associations with NHERF1 (Na+/H+ exchanger regulatory factor 1) protein. Besides, we assessed their impact on patients’ clinical outcome. We evaluated 220 primary BC samples by immunohistochemistry (IHC) and protein localization by immunofluorescence. We found a significant correlation between NHERF1 and FZD4, LRP5, LRP6, and TCF1. Univariate analysis showed that the overexpression of β-catenin (p < 0.0001), FZD4 (p = 0.0001), LRP5, LRP6, and TCF1 (p < 0.0001 respectively) was related to poor disease-free survival (DFS). A Kaplan-Meier analysis confirmed univariate data and showed a poor DFS for cNHERF1+/FZD4+ (p = 0.0007), cNHERF1+/LRP5+ (p = 0.0002), cNHERF1+/LRP6+ (p < 0.0001), and cNHERF1+/TCF1+ phenotypes (p = 0.0034). In multivariate analysis, the expression of TCF1 and β-catenin was an independent prognostic variable of worse DFS (p = 0.009 and p = 0.027, respectively). In conclusion, we found that the overexpression of β-catenin, FZD4, LRP5, LRP6, and TCF1 was associated with poor prognosis. Furthermore, we first identified TCF1 as an independent prognostic factor of poor outcome, indicating it as a new potential biomarker for the management of BC patients. Also, the expression of Wnt pathway proteins, both alone and in association with NHERF1, suggests original associations of biological significance for new studies.
Catalytic Activities of Multimeric G-Quadruplex DNAzymes
Authors: Adeoye Raphael I. , Osalaye Dunsin S. , Ralebitso-Senior Theresia K. , Boddis Amanda , Reid Amanda J. , Fatokun Amos A. , Powell Andrew K. , Malomo Sylvia O. , Olorunniji Femi J.
Published: July 2019

G-quadruplex DNAzymes are short DNA aptamers with repeating G4 quartets bound in a non-covalent complex with hemin. These G4/Hemin structures exhibit versatile peroxidase-like catalytic activity with a wide range of potential applications in biosensing and biotechnology. Current efforts are aimed at gaining a better understanding of the molecular mechanism of DNAzyme catalysis as well as devising strategies for improving their catalytic efficiency. Multimerisation of discrete units of G-quadruplexes to form multivalent DNAzyes is an emerging design strategy aimed at enhancing the peroxidase activities of DNAzymes. While this approach holds promise of generating more active multivalent G-quadruplex DNAzymes, few examples have been studied and it is not clear what factors determine the enhancement of catalytic activities of multimeric DNAzymes. In this study, we report the design and characterisation of multimers of five G-quadruplex sequences (AS1411, Bcl-2, c-MYC, PS5.M and PS2.M). Our results show that multimerisation of G-quadruplexes that form parallel structure (AS1411, Bcl-2, c-MYC) leads to significant rate enhancements characteristic of cooperative and/or synergistic interactions between the monomeric units. In contrast, multimerisation of DNA sequences that form non-parallel structures (PS5.M and PS2.M) did not exhibit similar levels of synergistic increase in activities. These results show that design of multivalent G4/Hemin structures could lead to a new set of versatile and efficient DNAzymes with enhanced capacity to catalyse peroxidase-mimic reactions.
Membrane Technology in Catalytic Carbonylation Reactions
Authors: Galiano Francesco , Castro-Muñoz Roberto , Mancuso Raffaella , Gabriele Bartolo , Figoli Alberto
Published: July 2019

In this review, the recent achievements on the use of membrane technologies in catalytic carbonylation reactions are described. The review starts with a general introduction on the use and function of membranes in assisting catalytic chemical reactions with a particular emphasis on the most widespread applications including esterification, oxidation and hydrogenation reactions. An independent paragraph will be then devoted to the state of the art of membranes in carbonylation reactions for the synthesis of dimethyl carbonate (DMC). Finally, the application of a specific membrane process, such as pervaporation, for the separation/purification of products deriving from carbonylation reactions will be presented.
Application of Microwave in Hydrogen Production from Methane Dry Reforming: Comparison Between the Conventional and Microwave-Assisted Catalytic Reforming on Improving the Energy Efficiency
Authors: Sharifvaghefi Seyyedmajid , Shirani Babak , Eic Mladen , Zheng Ying
Published: July 2019

The microwave-assisted dry reforming of methane over Ni and Ni–MgO catalysts supported on activated carbon (AC) was studied with respect to reducing reaction energy consumption. In order to optimize the reforming reaction using the microwave setup, an inclusive study was performed on the effect of operating parameters, including the type of catalysts’ active metal and their concentration in the AC support, feed flow rate, and reaction temperature on the reaction conversion and H2/CO selectivity. The methane dry reforming was also carried out using conventional heating and the results were compared to those of microwave heating. The catalysts’ activity was increased under microwave heating and as a result, the feed conversion and hydrogen selectivity were enhanced in comparison to the conventional heating method. In addition, to improve the reactants’ conversion and products’ selectivity, the thermal analysis also clarified the crucial importance of microwave heating in enhancing the energy efficiency of the reaction compared to the conventional heating.
Removal of Bound PAH Residues in Contaminated Soils by Fenton Oxidation
Authors: Zhao Xuqiang , Qin Li , Gatheru Waigi Michael , Cheng Pengfei , Yang Bing , Wang Jian , Ling Wanting
Published: July 2019

The availability of bound residues of polycyclic aromatic hydrocarbons (PAHs), in reference to their parent compounds, can be enhanced by microbial activity and chemical reactions, which pose severe risks for the ecosystems encompassing contaminated soils. Considerable attention has been raised on how to remove these bound residues from PAH-contaminated soils. This paper provides a novel application of Fenton oxidation in the removal of bound residues of model PAHs, such as naphthalene (NAP), acenaphthene (ACP), fluorene (FLU) and anthracene (ANT), from naturally contaminated soils. The citric acid-enhanced Fenton treatment resulted in the degradation of bound PAH residues that followed pseudo-first-order kinetics, with rate constants within 4.22 × 10−2, 1.25 × 10−1 and 2.72 × 10−1 h−1 for NAP, FLU, and ANT, respectively. The reactivity of bound PAH residues showed a correlation with their ionization potential (IP) values. Moreover, the degradation rate of bound PAH residues was significantly correlated with H2O2-Fe2+ ratio (m/m) and H2O2 concentrations. The highest removal efficiencies of bound PAH residues was up to 89.5% with the treatment of chelating agent oxalic acid, which was demonstrated to be superior to other acids, such as citric acid and hydrochloric acid. This study provides valuable insight into the feasibility of citric acid-Fenton and oxalic acid-Fenton treatments in rehabilitating bound PAH residues in contaminated soils.
Immobilization of a Novel ESTBAS Esterase from Bacillus altitudinis onto an Epoxy Resin: Characterization and Regioselective Synthesis of Chloramphenicol Palmitate
Authors: Dong Fengying , Tang Xudong , Yang Xiaohui , Lin Lin , He Dannong , Wei Wei , Wei Dongzhi
Published: July 2019

Novel gene estBAS from Bacillus altitudinis, encoding a 216-amino acid esterase (EstBAS) with a signal peptide (SP), was expressed in Escherichia coli. EstBASΔSP showed the highest activity toward p-nitrophenyl hexanoate at 50 °C and pH 8.0 and had a half-life (T1/2) of 6 h at 50 °C. EstBASΔSP was immobilized onto a novel epoxy resin (Lx-105s) with a high loading of 96 mg/g. Fourier transform infrared (FTIR) spectroscopy showed that EstBASΔSP was successfully immobilized onto Lx-105s. In addition, immobilization improved its enzymatic performance by widening the tolerable ranges of pH and temperature. The optimum temperature of immobilized EstBASΔSP (Lx-EstBASΔSP) was higher, 60 °C, and overall thermostability improved. T1/2 of Lx-EstBASΔSP and free EstBASΔSP at 60 °C was 105 and 28 min, respectively. Lx-EstBASΔSP was used as a biocatalyst to synthesize chloramphenicol palmitate by regioselective modification at the primary hydroxyl group. Conversion efficiency reached 94.7% at 0.15 M substrate concentration after 24 h. Lx-EstBASΔSP was stable and could be reused for seven cycles, after which it retained over 80% of the original activity.
Dextran Aldehyde in Biocatalysis: More Than a Mere Immobilization System
Authors: Tacias-Pascacio Veymar G. , Ortiz Claudia , Rueda Nazzoly , Berenguer-Murcia Ángel , Acosta Niuris , Aranaz Inmaculada , Civera Concepción , Fernandez-Lafuente Roberto , Alcántara Andrés R.
Published: July 2019

Dextran aldehyde (dexOx), resulting from the periodate oxidative cleavage of 1,2-diol moiety inside dextran, is a polymer that is very useful in many areas, including as a macromolecular carrier for drug delivery and other biomedical applications. In particular, it has been widely used for chemical engineering of enzymes, with the aim of designing better biocatalysts that possess improved catalytic properties, making them more stable and/or active for different catalytic reactions. This polymer possesses a very flexible hydrophilic structure, which becomes inert after chemical reduction; therefore, dexOx comes to be highly versatile in a biocatalyst design. This paper presents an overview of the multiple applications of dexOx in applied biocatalysis, e.g., to modulate the adsorption of biomolecules on carrier surfaces in affinity chromatography and biosensors design, to serve as a spacer arm between a ligand and the support in biomacromolecule immobilization procedures or to generate artificial microenvironments around the enzyme molecules or to stabilize multimeric enzymes by intersubunit crosslinking, among many other applications.
Efficient Photocatalytic Hydrogen Peroxide Production over TiO2 Passivated by SnO2
Authors: Zuo Guifu , Li Bingdong , Guo Zhaoliang , Wang Liang , Yang Fan , Hou Weishu , Zhang Songtao , Zong Peixiao , Liu Shanshan , Meng Xianguang , Du Yi , Wang Tao , Roy Vellaisamy A. L.
Published: July 2019

Photocatalysis provides an attractive strategy for synthesizing H2O2 at ambient condition. However, the photocatalytic synthesis of H2O2 is still limited due to the inefficiency of photocatalysts and decomposition of H2O2 during formation. Here, we report SnO2-TiO2 heterojunction photocatalysts for synthesizing H2O2 directly in aqueous solution. The SnO2 passivation suppresses the complexation and decomposition of H2O2 on TiO2. In addition, loading of Au cocatalyst on SnO2-TiO2 heterojunction further improves the production of H2O2. The in situ electron spin resonance study revealed that the formation of H2O2 is a stepwise single electron oxygen reduction reaction (ORR) for Au and SnO2 modified TiO2 photocatalysts. We demonstrate that it is feasible to enhance H2O2 formation and suppress H2O2 decomposition by surface passivation of the H2O2-decomposition-sensitive photocatalysts.
Facile Synthesis of Heterojunctioned ZnO/Bi2S3 Nanocomposites for Enhanced Photocatalytic Reduction of Aqueous Cr(VI) under Visible-Light Irradiation
Authors: Yuan Xiaoya , Wu Xue , Feng Zijuan , Jia Wen , Zheng Xuxu , Li Chuanqiang
Published: July 2019

Heterojunctioned ZnO/Bi2S3 nanocomposites were prepared via a facile solvothermal method. The obtained photocatalysts were characterized by X-ray powder diffraction (XRD), Scanning electron microscopy (SEM), High resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), UV-Vis diffuse reflectance spectroscopy (DRS), and Photoelectrochemical and Photoluminescence spectroscopy (PL), respectively. The results showed that ZnO/Bi2S3 composites exhibited the sandwiched-like structure, where ZnO nanoparticles were randomly embedded between Bi2S3 nanoflakes. The performance of photocatalytic Cr(VI) reduction under visible light indicated that ZnO/Bi2S3 composites exhibited high-efficiency photocatalytic activity in comparison with either Bi2S3 or ZnO. The 5%-ZnO/Bi2S3 photocatalyst removed 96% of Cr(VI) within 120 min at 20 mg/L initial concentration of Cr(VI). The enhanced performance of ZnO/Bi2S3 photocatalysts could be ascribed to the increased light harvesting and the effective separation and transfer of the photogenerated charge carriers across the heterojunction interface of the ZnO/Bi2S3 composite. This work could pave the way for the design of new hetero-structured materials and has great potential in environmental remediation.
Pyrolysis Kinetics of Hydrochars Produced from Brewer’s Spent Grains
Authors: Olszewski Maciej P. , Arauzo Pablo J. , Maziarka Przemyslaw A. , Ronsse Frederik , Kruse Andrea
Published: July 2019

The current market situation shows that large quantities of the brewer’s spent grains (BSG)—the leftovers from the beer productions—are not fully utilized as cattle feed. The untapped BSG is a promising feedstock for cheap and environmentally friendly production of carbonaceous materials in thermochemical processes like hydrothermal carbonization (HTC) or pyrolysis. The use of a singular process results in the production of inappropriate material (HTC) or insufficient economic feasibility (pyrolysis), which hinders their application on a larger scale. The coupling of both processes can create synergies and allow the mentioned obstacles to be overcome. To investigate the possibility of coupling both processes, we analyzed the thermal degradation of raw BSG and BSG-derived hydrochars and assessed the solid material yield from the singular as well as the coupled processes. This publication reports the non-isothermal kinetic parameters of pyrolytic degradation of BSG and derived hydrochars produced in three different conditions (temperature-retention time). It also contains a summary of their pyrolytic char yield at four different temperatures. The obtained KAS (Kissinger–Akahira–Sunose) average activation energy was 285, 147, 170, and 188 kJ mol−1 for BSG, HTC-180-4, HTC-220-2, and HTC-220-4, respectively. The pyrochar yield for all hydrochar cases was significantly higher than for BSG, and it increased with the severity of the HTC’s conditions. The results reveal synergies resulting from coupling both processes, both in the yield and the reduction of the thermal load of the conversion process. According to these promising results, the coupling of both conversion processes can be beneficial. Nevertheless, drying and overall energy efficiency, as well as larger scale assessment, still need to be conducted to fully confirm the concept.
Electromagnetic Effective Medium Modelling of Composites with Metal-Semiconductor Core-Shell Type Inclusions
Authors: Gutiérrez Yael , Ortiz Dolores , Alcaraz de la Osa Rodrigo , Saiz José , González Francisco , Moreno Fernando
Published: July 2019

The possibility of using light to drive chemical reactions has highlighted the role of photocatalysis as a key tool to address the environmental and energy issues faced by today’s society. Plasmonic photocatalysis, proposed to circumvent some of the problems of conventional semiconductor catalysis, uses hetero-nanostructures composed by plasmonic metals and semiconductors as catalysts. Metal-semiconductor core-shell nanoparticles present advantages (i.e., protecting the metal and enlarging the active sites) with respect to other hetero-nanostructures proposed for plasmonic photocatalysis applications. In order to maximize light absorption in the catalyst, it is critical to accurately model the reflectance/absorptance/transmittance of composites and colloids with metal-semiconductor core-shell nanoparticle inclusions. Here, we present a new method for calculating the effective dielectric function of metal-semiconductor core-shell nanoparticles and its comparison with existing theories showing clear advantages. Particularly, this new method has shown the best performance in the prediction of the spectral position of the localized plasmonic resonances, a key parameter in the design of efficient photocatalysts. This new approach can be considered as a useful tool for designing coated particles with desired plasmonic properties and engineering the effective permittivity of composites with core-shell type inclusions which are used in photocatalysis and solar energy harvesting applications.
Light-Induced Reactions of Chlorpromazine in the Presence of a Heterogeneous Photocatalyst: Formation of a Long-Lasting Sulfoxide
Authors: Arimi Arsou , Dillert Ralf , Dräger Gerald , Bahnemann Detlef W.
Published: July 2019

A commercial carbon-modified titanium dioxide, KRONOClean 7000, was applied as a UV(A) and visible-light active photocatalyst to investigate the conversion of the antipsychotic pharmaceutical chlorpromazine in aqueous phase employing two monochromatic light sources emitting at wavelengths of 365 and 455 nm. Photocatalytic and photolytic conversion of chlorpromazine under both anaerobic and aerobic conditions was analyzed using a HPLC-MS technique. Depending on the irradiation wavelength and presence of oxygen, varying conversion rates and intermediates revealing different reaction pathways were observed. Upon visible light irradiation under aerobic conditions, chlorpromazine was only converted in the presence of the photocatalyst. No photocatalytic conversion of this compound under anaerobic conditions upon visible light irradiation was observed. Upon UV(A) irradiation, chlorpromazine was successfully converted into its metabolites in both presence and absence of the photocatalyst. Most importantly, chlorpromazine sulfoxide, a very persistent metabolite of chlorpromazine, was produced throughout the photolytic and photocatalytic conversions of chlorpromazine under aerobic conditions. Chlorpromazine sulfoxide was found to be highly stable under visible light irradiation even in the presence of the photocatalyst. Heterogeneous photocatalysis under UV(A) irradiation resulted in a slow decrease of the sulfoxide concentration, however, the required irradiation time for its complete removal was found to be much longer compared to the removal of chlorpromazine at the same initial concentration.
Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis
Authors: Valenti Maria Teresa , Deiana Michela , Cheri Samuele , Dotta Monica , Zamboni Francesco , Gabbiani Daniele , Schena Federico , Dalle Carbonare Luca , Mottes Monica
Published: July 2019

Physical exercise is known to promote beneficial effects on overall health, counteracting risks related to degenerative diseases. MicroRNAs (miRNAs), short non-coding RNAs affecting the expression of a cell’s transcriptome, can be modulated by different stimuli. Yet, the molecular effects on osteogenic differentiation triggered by miRNAs upon physical exercise are not completely understood. In this study, we recruited 20 male amateur runners participating in a half marathon. Runners’ sera, collected before (PRE RUN) and after (POST RUN) the run, were added to cultured human mesenchymal stromal cells. We then investigated their effects on the modulation of selected miRNAs and the consequential effects on osteogenic differentiation. Our results showed an increased expression of miRNAs promoting osteogenic differentiation (miR-21-5p, miR-129-5p, and miR-378-5p) and a reduced expression of miRNAs involved in the adipogenic differentiation of progenitor cells (miR-188-5p). In addition, we observed the downregulation of PTEN and SMAD7 expression along with increased AKT/pAKT and SMAD4 protein levels in MSCs treated with POST RUN sera. The consequent upregulation of RUNX2 expression was also proven, highlighting the molecular mechanisms by which miR-21-5p promotes osteogenic differentiation. In conclusion, our work proposes novel data, which demonstrate how miRNAs may regulate the osteogenic commitment of progenitor cells in response to physical exercise.
Large Scale Profiling of Protein Isoforms Using Label-Free Quantitative Proteomics Revealed the Regulation of Nonsense-Mediated Decay in Moso Bamboo (Phyllostachys edulis)
Authors: Yu Xiaolan , Wang Yongsheng , Kohnen Markus V. , Piao Mingxin , Tu Min , Gao Yubang , Lin Chentao , Zuo Zecheng , Gu Lianfeng
Published: July 2019

Moso bamboo is an important forest species with a variety of ecological, economic, and cultural values. However, the gene annotation information of moso bamboo is only based on the transcriptome sequencing, lacking the evidence of proteome. The lignification and fiber in moso bamboo leads to a difficulty in the extraction of protein using conventional methods, which seriously hinders research on the proteomics of moso bamboo. The purpose of this study is to establish efficient methods for extracting the total proteins from moso bamboo for following mass spectrometry-based quantitative proteome identification. Here, we have successfully established a set of efficient methods for extracting total proteins of moso bamboo followed by mass spectrometry-based label-free quantitative proteome identification, which further improved the protein annotation of moso bamboo genes. In this study, 10,376 predicted coding genes were confirmed by quantitative proteomics, accounting for 35.8% of all annotated protein-coding genes. Proteome analysis also revealed the protein-coding potential of 1015 predicted long noncoding RNA (lncRNA), accounting for 51.03% of annotated lncRNAs. Thus, mass spectrometry-based proteomics provides a reliable method for gene annotation. Especially, quantitative proteomics revealed the translation patterns of proteins in moso bamboo. In addition, the 3284 transcript isoforms from 2663 genes identified by Pacific BioSciences (PacBio) single-molecule real-time long-read isoform sequencing (Iso-Seq) was confirmed on the protein level by mass spectrometry. Furthermore, domain analysis of mass spectrometry-identified proteins encoded in the same genomic locus revealed variations in domain composition pointing towards a functional diversification of protein isoform. Finally, we found that part transcripts targeted by nonsense-mediated mRNA decay (NMD) could also be translated into proteins. In summary, proteomic analysis in this study improves the proteomics-assisted genome annotation of moso bamboo and is valuable to the large-scale research of functional genomics in moso bamboo. In summary, this study provided a theoretical basis and technical support for directional gene function analysis at the proteomics level in moso bamboo.
Dual Roles of the AMP-Activated Protein Kinase Pathway in Angiogenesis
Authors: Li Yuanjun , Sun Ruipu , Zou Junrong , Ying Ying , Luo Zhijun
Published: July 2019

Angiogenesis plays important roles in development, stress response, wound healing, tumorigenesis and cancer progression, diabetic retinopathy, and age-related macular degeneration. It is a complex event engaging many signaling pathways including vascular endothelial growth factor (VEGF), Notch, transforming growth factor-beta/bone morphogenetic proteins (TGF-β/BMPs), and other cytokines and growth factors. Almost all of them eventually funnel to two crucial molecules, VEGF and hypoxia-inducing factor-1 alpha (HIF-1α) whose expressions could change under both physiological and pathological conditions. Hypoxic conditions stabilize HIF-1α, while it is upregulated by many oncogenic factors under normaxia. HIF-1α is a critical transcription activator for VEGF. Recent studies have shown that intracellular metabolic state participates in regulation of sprouting angiogenesis, which may involve AMP-activated protein kinase (AMPK). Indeed, AMPK has been shown to exert both positive and negative effects on angiogenesis. On the one hand, activation of AMPK mediates stress responses to facilitate autophagy which stabilizes HIF-1α, leading to increased expression of VEGF. On the other hand, AMPK could attenuate angiogenesis induced by tumor-promoting and pro-metastatic factors, such as the phosphoinositide 3-kinase /protein kinase B (Akt)/mammalian target of rapamycin (PI3K/Akt/mTOR), hepatic growth factor (HGF), and TGF-β/BMP signaling pathways. Thus, this review will summarize research progresses on these two opposite effects and discuss the mechanisms behind the discrepant findings.
The IL4I1 Enzyme: A New Player in the Immunosuppressive Tumor Microenvironment
Authors: Molinier-Frenkel Valérie , Prévost-Blondel Armelle , Castellano Flavia
Published: July 2019

The high metabolic needs of T lymphocytes in response to activation make them particularly vulnerable to modifications of their biochemical milieu. Immunosuppressive enzymes produced in the tumor microenvironment modify nutrient availability by catabolizing essential or semi-essential amino acids and producing toxic catabolites, thus participating in the local sabotage of the antitumor immune response. L-amino-acid oxidases are FAD-bound enzymes found throughout evolution, from bacteria to mammals, and are often endowed with anti-infectious properties. IL4I1 is a secreted L-phenylalanine oxidase mainly produced by inflammatory antigen-presenting cells—in particular, macrophages present in T helper type 1 granulomas and in various types of tumors. In the last decade, it has been shown that IL4I1 is involved in the fine control of B- and T-cell adaptive immune responses. Preclinical models have revealed its role in cancer immune evasion. Recent clinical data highlight IL4I1 as a new potential prognostic marker in human melanoma. As a secreted enzyme, IL4I1 may represent an easily targetable molecule for cancer immunotherapy.
Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer
Authors: Yoshida Saori , Kawai Hotaka , Eguchi Takanori , Sukegawa Shintaro , Oo May Wathone , Anqi Chang , Takabatake Kiyofumi , Nakano Keisuke , Okamoto Kuniaki , Nagatsuka Hitoshi
Published: July 2019

CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To uncover the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as tumor angiogenic inhibition triggered necrosis (TAITN), which was induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic areas with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.
Regulation of Acetylcholine Quantal Release by Coupled Thrombin/BDNF Signaling in Mouse Motor Synapses
Authors: Gaydukov Alexander , Bogacheva Polina , Tarasova Ekaterina , Molchanova Anastasia , Miteva Anna , Pravdivceva Ekaterina , Balezina Olga
Published: July 2019

The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recordings of MEPPs and EPPs were used to evaluate the changes in acetylcholine (ACh) release in mature and newly-formed mouse NMJs. Thrombin (1 nM) increased the amplitude of MEPPs and EPPs by 25–30% in mature and newly-formed NMJs. This effect was due to an enhanced loading of synaptic vesicles with ACh and increase of ACh quantal size, since it was fully prevented by blocking of vesicular ACh transporter. It was also prevented by tropomyosin-related kinase B (TrkB) receptors inhibitor ANA12. Exogenous BDNF (1 nM) mimicked thrombin effect and increased the amplitude of MEPPs and EPPs by 25–30%. It required involvement of protein kinase A (PKA) and mitogen-activated protein kinase (MEK1/2)-mediated pathway, but not phospholipase C (PLC). Blocking A2A adenosine receptors by ZM241385 abolished the effect of BDNF, whereas additional stimulation of A2A receptors by CGS21680 increased MEPP amplitudes, which was prevented by MEK1/2 inhibitor U0126. At mature NMJs, BDNF enhanced MEPPs frequency by 30–40%. This effect was selectively prevented by inhibition of PLC, but not PKA or MEK1/2. It is suggested that interrelated effects of thrombin/BDNF in mature and newly-formed NMJs are realized via enhancement of vesicular ACh transport and quantal size increase. BDNF-induced potentiation of synaptic transmission involves the functional coupling between A2A receptor-dependent active PKA and neurotrophin-triggered MAPK pathway, as well as PLC-dependent increase in frequency of MEPPs.
Spreading and Imbibition of Vesicle Dispersion Droplets on Porous Substrates
Authors: Kumar Abhijeet , Kleinen Jochen , Venzmer Joachim , Trybala Anna , Starov Victor , Gambaryan-Roisman Tatiana
Published: July 2019

Vesicles have recently found widespread use in applications such as conditioning of textiles, paper and hair, as well as transdermal drug delivery. The mode of treatment in several such cases involves the application of droplets of aqueous dispersions of vesicles onto dry porous substrates like paper and textiles. One of the factors which affects the performance of such treatments is the rate at which the droplets spread and imbibe on the porous substrate. Depending upon the specific purpose of the treatment either a fast or slow droplet spreading kinetics could be desired. Therefore, it is important to have a good understanding of the droplet spreading process and the factors which influence it. In this work, an experimental investigation of the simultaneous spreading and imbibition of vesicle dispersion droplets on cellulose filter papers is carried out. Two different types of vesicles which are composed of similar lipid molecules but exhibit contrasting lipid bilayer phase behavior are used. Two different grades of filter papers with comparable porosities but different thicknesses are used as porous substrate. It is found that the droplet spreading behavior is of the “complete wetting” type on the thicker porous substrate, whereas it is of the “partial wetting” type on the thinner substrate. Furthermore, it is observed that the spreading of droplets containing vesicles with liquid-crystalline phase bilayers occurs faster than that of vesicles with solid-gel phase bilayers. The secondary radial penetration which commences after the initial droplet spreading is complete is also investigated and discussed.
Semantic Features for Optimizing Supervised Approach of Sentiment Analysis on Product Reviews
Authors: Setya Rintyarna Bagus , Sarno Riyanarto , Fatichah Chastine
Published: July 2019

The growth of ecommerce has triggered online reviews as a rich source of product information. Revealing consumer sentiment from the reviews through Sentiment Analysis (SA) is an important task of online product review analysis. Two popular approaches of SA are the supervised approach and the lexicon-based approach. In supervised approach, the employed machine learning (ML) algorithm is not the only one to influence the results of SA. The utilized text features also handle an important role in determining the performance of SA tasks. In this regard, we proposed a method to extract text features that takes into account semantic of words. We argue that this semantic feature is capable of augmenting the results of supervised SA tasks compared to commonly utilized features, i.e., bag-of-words (BoW). To extract the features, we assigned the correct sense of the word in reviewing the sentence by adopting a Word Sense Disambiguation (WSD) technique. Several WordNet similarity algorithms were involved, and correct sentiment values were assigned to words. Accordingly, we generated text features for product review documents. To evaluate the performance of our text features in the supervised approach, we conducted experiments using several ML algorithms and feature selection methods. The results of the experiments using 10-fold cross-validation indicated that our proposed semantic features favorably increased the performance of SA by 10.9%, 9.2%, and 10.6% of precision, recall, and F-Measure, respectively, compared with baseline methods.
Systematic Design of Crystal Structure for Hofmann-Like Spin Crossover Fe(L)2[Ag(CN)2]2 Complexes
Authors: Kosone Takashi , Makido Yoshinori , Okuda Syogo , Haigo Ayaka , Kawasaki Takeshi , Akahoshi Daisuke , Saito Toshiaki , Kitazawa Takafumi
Published: July 2019

The synthesis, crystal structures, and magnetic properties of a new two-dimensional (2D) Hofmann-like series, FeII(L)2[AgI(CN)2]2 (L = 3-cyano-4-methylpyridine (1), allyl isonicotinate (2), phenyl-isonicotinate (3), and benzyl nicotinate (4)) were studied. These compounds have a 2D sheet structure because of their strongly determinate self-assembly process. An octahedral FeII ion is coordinated with the nitrogen atoms of[AgI(CN)2 linear units at equatorial positions and monodentate pyridine derivatives at the axial position. The layers construct a parallel stacking array. Compounds 1–3 show pairs of layers constructed by intermetallic Ag···Ag interactions. Compound 4 shows a mono-layer structure. The substituent bulk of the ligands affects the interlayer space. Compounds 1–4 undergo a 100% spin transition. However, compound 1, incorporating a smaller group, has a relatively lower critical temperature (Tc = 182 K (1), Tc = 221 K (2), Tc = 227 (3) and Tc1 = 236 K, Tc2 = 215 K (4)). We investigated the correlations between our systematic crystal design, substituent size, and the spin crossover profiles.
Growth from the Melt and Properties Investigation of ScF3 Single Crystals
Authors: Karimov Denis , Buchinskaya Irina , Arkharova Natalia , Prosekov Pavel , Grebenev Vadim , Sorokin Nikolay , Glushkova Tatiana , Popov Pavel
Published: July 2019

ScF3 optical quality bulk crystals of the ReO3 structure type (space group P m 3 ¯ m , a = 4.01401(3) Å) have been grown from the melt by Bridgman technique, in fluorinating atmosphere for the first time. Aiming to substantially reduce vaporization losses during the growth process graphite crucibles were designed. The crystal quality, optical, mechanical, thermal and electrophysical properties were studied. Novel ScF3 crystals refer to the low-refractive-index (nD = 1.400(1)) optical materials with high transparency in the visible and IR spectral region up to 8.7 µm. The Vickers hardness of ScF3 (HV ~ 2.6 GPa) is substantially higher than that of CaF2 and LaF3 crystals. ScF3 crystals possess unique high thermal conductivity (k = 9.6 Wm−1К−1 at 300 K) and low ionic conductivity (σ = 4 × 10−8 Scm−1 at 673 К) cause to the structural defects in the fluorine sublattice.