bluuebunny/crossref_metadata_2025 huggingface dataset:
Sporadic Inclusion Body Myositis: An Acquired Mitochondrial Disease with Extras
Authors: De Paepe Boel
Published: January 2019

The sporadic form of inclusion body myositis (IBM) is the most common late-onset myopathy. Its complex pathogenesis includes degenerative, inflammatory and mitochondrial aspects. However, which of those mechanisms are cause and which effect, as well as their interrelations, remain partly obscured to this day. In this review the nature of the mitochondrial dysregulation in IBM muscle is explored and comparison is made with other muscle disorders. Mitochondrial alterations in IBM are evidenced by histological and serum biomarkers. Muscular mitochondrial dynamics is disturbed, with deregulated organelle fusion leading to subsequent morphological alterations and muscle displays abnormal mitophagy. The tissue increases mitochondrial content in an attempt to compensate dysfunction, yet mitochondrial DNA (mtDNA) alterations and mild mtDNA depletion are also present. Oxidative phosphorylation defects have repeatedly been shown, most notably a reduction in complex IV activities and levels of mitokines and regulatory RNAs are perturbed. Based on the cumulating evidence of mitochondrial abnormality as a disease contributor, it is therefore warranted to regard IBM as a mitochondrial disease, offering a feasible therapeutic target to be developed for this yet untreatable condition.
High Glucose Represses the Anti-Proliferative and Pro-Apoptotic Effect of Metformin in Triple Negative Breast Cancer Cells
Authors: Varghese Sharon , Samuel Samson Mathews , Varghese Elizabeth , Kubatka Peter , Büsselberg Dietrich
Published: January 2019

Metformin, the most widely prescribed anti-diabetic drug, is shown to possess anti-cancer potential in treatment of cancers, including breast cancer; decreases breast cancer risk; and improves overall survival. However, reports suggest that higher glucose concentrations may negatively impact the anti-cancer efficacy of metformin. Therefore, we examined the anti-cancer potential of metformin in triple-negative breast cancer cells (TNBCs) exposed to different glucose (25 mM, 5.5 mM and zero glucose/glucose-starved) conditions. Our data indicates that a high glucose (25 mM) concentration (mimicking diabetes) significantly abrogated the effect of metformin on cell proliferation, cell death and cell cycle arrest in addition to loss of efficacy in inhibition of the mTOR pathway, a key metabolic pathway in TNBC cells. The mTOR pathway is activated in TNBCs compared to other subtypes of breast cancer, regulates the synthesis of proteins that are critical for the growth and survival of cancer cells and its activation is correlated to poor outcomes among TNBC patients, while also contributing to metastatic progression and development of resistance to chemotherapy/radiotherapy. Our studies were performed in two different types of TNBCs, MDA-MB-231 cells (mesenchymal stem cell-like (MSL)) and MDA-MB-468 (basal like-1 (BL-1)). Interestingly, lower concentrations of metformin (50, 100, 250, and 500 μM) significantly increased cell proliferation in 25 mM glucose exposed MDA-MB-231 cells, an effect which was not observed in MDA-MB-468 cells, indicating that the effective concentration of metformin when used as anti-cancer drug in TNBCs may have to be determined based on cell type and blood glucose concentration. Our data indicates that metformin treatment was most effective under zero glucose/glucose-starved conditions in MDA-MB-468 with a significant increase in the apoptotic population (62.3 ± 1.5%; p-value < 0.01). Under 5.5 mM glucose conditions in both MDA-MB-231 and MDA-MB-468 cells our data showed reduced viability of 73.56 ± 2.53%; p-value < 0.05 and 70.49 ± 1.68%; p-value < 0.001, respectively, along with a significant increase in apoptotic populations of both cell types. Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals.
Longitudinal Study of Delta-Aminolevulinate Dehydratase Activity and Oxidative Profile in Healthy Pregnant Women
Authors: de Lucca Leidiane , Jantsch Letícia Bigolin , Vendrame Silmara Ana , Stein Carolina dos Santos , Klein Vanessa Cristina Grólli , Soares Karina Biaggio , Gallarreta Francisco Maximiliano Pancich , Moresco Rafael Noal , Gonçalves Thissiane de Lima
Published: January 2019

Pregnancy is characterized by changes in various organs, triggering changes in the use of energy substrates and increased oxygen consumption. In addition, gestation is an oxidative event that can be assessed by the relationship between free radicals and antioxidants produced by the body. Excessive production of free radicals has detrimental effects such as damage to enzymes, carbohydrates, and DNA. Thus, the objective of this study was to evaluate the oxidative status and antioxidant responses throughout pregnancy through a longitudinal study. Reactive oxygen species were analyzed by means of thiobarbituric acid reactive substances and nitric oxide, the antioxidant system through vitamin C, sulfhydryl groups, total antioxidant capacity, and ferric reducing ability of plasma as well as enzymes such as catalase and delta-aminolevulinate-dehydratase in pregnant women in the three gestational trimesters (n = 30). According to the results, the markers of oxidative damage showed significant differences in the different gestational trimesters where they were increased in the second trimester when compared to the first trimester. The antioxidant defenses responded differently in each gestational trimester, suggesting a response pattern to try to combat the damage caused by free radicals, in order to stabilize the increase of oxidative stress caused in the second gestational trimester.
Energy Transfer between Tm-Doped Upconverting Nanoparticles and a Small Organic Dye with Large Stokes Shift
Authors: López de Guereñu Anna , Bastian Philipp , Wessig Pablo , John Leonard , Kumke Michael U.
Published: January 2019

Lanthanide-doped upconverting nanoparticles (UCNP) are being extensively studied for bioapplications due to their unique photoluminescence properties and low toxicity. Interest in RET applications involving UCNP is also increasing, but due to factors such as large sizes, ion emission distributions within the particles, and complicated energy transfer processes within the UCNP, there are still many questions to be answered. In this study, four types of core and core-shell NaYF4-based UCNP co-doped with Yb3+ and Tm3+ as sensitizer and activator, respectively, were investigated as donors for the Methyl 5-(8-decanoylbenzo[1,2-d:4,5-d′]bis([1,3]dioxole)-4-yl)-5-oxopentanoate (DBD-6) dye. The possibility of resonance energy transfer (RET) between UCNP and the DBD-6 attached to their surface was demonstrated based on the comparison of luminescence intensities, band ratios, and decay kinetics. The architecture of UCNP influenced both the luminescence properties and the energy transfer to the dye: UCNP with an inert shell were the brightest, but their RET efficiency was the lowest (17%). Nanoparticles with Tm3+ only in the shell have revealed the highest RET efficiencies (up to 51%) despite the compromised luminescence due to surface quenching.
A Bioelectronic System to Measure the Glycolytic Metabolism of Activated CD4+ T Cells
Authors: Crowe Suzanne M. , Kintzios Spyridon , Kaltsas Grigoris , Palmer Clovis S.
Published: January 2019

The evaluation of glucose metabolic activity in immune cells is becoming an increasingly standard task in immunological research. In this study, we described a sensitive, inexpensive, and non-radioactive assay for the direct and rapid measurement of the metabolic activity of CD4+ T cells in culture. A portable, custom-built Cell Culture Metabolite Biosensor device was designed to measure the levels of acidification (a proxy for glycolysis) in cell-free CD4+ T cell culture media. In this assay, ex vivo activated CD4+ T cells were incubated in culture medium and mini electrodes were placed inside the cell free culture filtrates in 96-well plates. Using this technique, the inhibitors of glycolysis were shown to suppress acidification of the cell culture media, a response similar to that observed using a gold standard lactate assay kit. Our findings show that this innovative biosensor technology has potential for applications in metabolic research, where acquisition of sufficient cellular material for ex vivo analyses presents a substantial challenge.
Human Factors in Green Building: Building Types and Users’ Needs
Authors: Gou Zhonghua
Published: January 2019

The Special Issue on “Human Factors in Green Building” addresses the design of indoor environment quality for users’ needs. The collected papers cover various building types and the research highlights the different needs of users. In working environments, employees’ stress is the main concern in the workplace design, especially for open plan offices where lack of privacy and over exposure to environmental stress have been reported. In residential environments, residents have great opportunities to adjust their environments to suit their needs; therefore, passive design such as natural ventilation is explored in residential buildings with climates such as cold or humid tropical. In healthcare environments, the papers in this issue are concerned with the needs of patients, especially the older adults who require special care. In learning environments, thermal and visual aspects are investigated for optimal comfort conditions and learning outcomes. The special issue demonstrates insightful critical thinking of indoor environment quality and proposes a new understanding for more practical design solutions. This editorial note is a brief review of the 12 papers, concluding with reflections about design of built environments to meet users’ needs.
Assessment of Progressive Collapse Resistance of Steel Structures with Moment Resisting Frames
Authors: Mohamed Osama , Khattab Rania
Published: January 2019

This paper evaluates the practice of using moment connections in the perimeter of the structural system and shear connections within the interior connections of the three-dimensional structural system from the perspective of resistance to progressive collapse. The enhanced resistance to progressive collapse associated with using moment resisting connections at the perimeter as well as internal to the three-dimensional system is assessed. Progressive collapse occurrence and system resistance are determined using the alternate path method which presumes a primary load carrying-member is notionally removed. The paper compares the structural response determined using linear elastic, non-linear elastic and non-linear dynamic analyses. Linear and non-linear static analyses are found to be incapable of capturing the response pursuant to the loss of the primary load carrying member. The analysis procedures used in this study followed (for the most part) the United States Department of Defense Guide for Progressive Collapse Resistant Design of Structures.
Experimental Investigation of the Mechanisms of Salt Precipitation during CO2 Injection in Sandstone
Authors: Sokama-Neuyam Yen Adams , Ursin Jann Rune , Boakye Patrick
Published: January 2019

Deep saline reservoirs have the highest volumetric CO2 storage potential, but drying and salt precipitation during CO2 injection could severely impair CO2 injectivity. The physical mechanisms and impact of salt precipitation, especially in the injection area, is still not fully understood. Core-flood experiments were conducted to investigate the mechanisms of external and internal salt precipitation in sandstone rocks. CO2 Low Salinity Alternating Gas (CO2-LSWAG) injection as a potential mitigation technique to reduce injectivity impairment induced by salt precipitation was also studied. We found that poor sweep and high brine salinity could increase salt deposition on the surface of the injection area. The results also indicate that the amount of salt precipitated in the dry-out zone does not change significantly during the drying process, as large portion of the precipitated salt accumulate in the injection vicinity. However, the distribution of salt in the dry-out zone was found to change markedly when more CO2 was injected after salt precipitation. This suggests that CO2 injectivity impairment induced by salt precipitation is probably dynamic rather than a static process. It was also found that CO2-LSWAG could improve CO2 injectivity after salt precipitation. However, below a critical diluent brine salinity, CO2-LSWAG did not improve injectivity. These findings provide vital understanding of core-scale physical mechanisms of the impact of salt precipitation on CO2 injectivity in saline reservoirs. The insight gained could be implemented in simulation models to improve the quantification of injectivity losses during CO2 injection into saline sandstone reservoirs.
Direct Oral Anticoagulant Drugs: On the Treatment of Cancer-Related Venous Thromboembolism and their Potential Anti-Neoplastic Effect
Authors: Grandoni Francesco , Alberio Lorenzo
Published: January 2019

Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism.
Prognostic Gene Discovery in Glioblastoma Patients using Deep Learning
Authors: Wong Kelvin K. , Rostomily Robert , Wong Stephen T. C.
Published: January 2019

This study aims to discover genes with prognostic potential for glioblastoma (GBM) patients’ survival in a patient group that has gone through standard of care treatments including surgeries and chemotherapies, using tumor gene expression at initial diagnosis before treatment. The Cancer Genome Atlas (TCGA) GBM gene expression data are used as inputs to build a deep multilayer perceptron network to predict patient survival risk using partial likelihood as loss function. Genes that are important to the model are identified by the input permutation method. Univariate and multivariate Cox survival models are used to assess the predictive value of deep learned features in addition to clinical, mutation, and methylation factors. The prediction performance of the deep learning method was compared to other machine learning methods including the ridge, adaptive Lasso, and elastic net Cox regression models. Twenty-seven deep-learned features are extracted through deep learning to predict overall survival. The top 10 ranked genes with the highest impact on these features are related to glioblastoma stem cells, stem cell niche environment, and treatment resistance mechanisms, including POSTN, TNR, BCAN, GAD1, TMSB15B, SCG3, PLA2G2A, NNMT, CHI3L1 and ELAVL4.
Prognostic Factors for Advanced Pancreatic Cancer Treated with Gemcitabine Plus S-1: Retrospective Analysis and Development of a Prognostic Model
Authors: Chang Ching-Fu , Huang Pei-Wei , Chen Jen-Shi , Chen Yen-Yang , Lu Chang-Hsien , Chang Pei-Hung , Hung Yu-Shin , Chou Wen-Chi
Published: January 2019

Gemcitabine plus S-1 (GS) is commonly used to treat advanced pancreatic cancer (APC) in Asia. Few clinical experiments have demonstrated the clinical efficacy of GS in routine clinical practice. We aimed to identify the prognostic factors and develop a prognostic model for survival prediction in patients with APC, treated with GS. Records of 111 patients with newly diagnosed APC who received first-line palliative GS chemotherapy during 2010–2016 in Taiwan were analyzed retrospectively. Univariate and multivariate analyses were performed for the identification of prognostic factors. A prognostic model using prognosticators from the multivariate analysis was developed for survival prediction. The median overall survival (OS) for the cohort was 9.3 months (95% confidence interval [CI], 8.0–10.6). The prognostic model was constructed based on four independent prognosticators: performance status, tumor stage, pre-treatment albumin level, and neutrophil-to-lymphocyte ratio. Patients were categorized by tertiles into good, intermediate, and poor prognostic groups. The median OS values for each of these groups were 21.1 (95% CI, 8.2–33.9), 9.2 (95% CI, 8.3–10.1), and 5.8 months (95% CI, 4.4–7.1; log-rank p < 0.001), respectively. The bootstrapped corrected C-index of this model was 0.80 (95% CI, 0.71–0.89). The developed model was robust and could accurately predict survival in this population, and can assist clinicians and patients in survival discrimination and the determination of appropriate medical care goals. Additional research is needed to externally validate the model’s performance.
Spectrum of Epithelial-Mesenchymal Transition Phenotypes in Circulating Tumour Cells from Early Breast Cancer Patients
Authors: Markiewicz Aleksandra , Topa Justyna , Nagel Anna , Skokowski Jaroslaw , Seroczynska Barbara , Stokowy Tomasz , Welnicka-Jaskiewicz Marzena , Zaczek Anna J.
Published: January 2019

Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients. We have obtained CTCs-enriched blood fraction from 83 breast cancer patients in which we have tested the expression of epithelial, mesenchymal and general breast cancer CTCs markers (MGB1/HER2/CK19/CDH1/CDH2/VIM/PLS3), cancer stem cell markers (CD44, NANOG, ALDH1, OCT-4, CD133) and cluster formation gene (plakoglobin). We have shown that in the CTCs-positive patients, epithelial, epithelial-mesenchymal and mesenchymal CTCs markers were detected at a similar rate (in 28%, 24% and 24%, respectively). Mesenchymal CTCs were characterized by the most aggressive phenotype (significantly higher expression of CXCR4, uPAR, CD44, NANOG, p < 0.05 for all), presence of lymph node metastases (p = 0.043), larger tumour size (p = 0.023) and 7.33 higher risk of death in the multivariate analysis (95% CI 1.06–50.41, p = 0.04). Epithelial-mesenchymal subtype, believed to correspond to highly plastic and aggressive state, did not show significant impact on survival. Gene expression profile of samples with epithelial-mesenchymal CTCs group resembled pure epithelial or pure mesenchymal phenotypes, possibly underlining degree of EMT activation in particular patient’s sample. Molecular profiling of CTCs EMT phenotype provides more detailed and clinically informative results, proving the role of EMT in malignant cancer progression in early breast cancer.
Ozone and Photocatalytic Processes for Pathogens Removal from Water: A Review
Authors: Gomes João , Matos Ana , Gmurek Marta , Quinta-Ferreira Rosa M. , Martins Rui C.
Published: January 2019

The search for alternative water sources is pushing to the reuse of treated water coming from municipal wastewater treatment plants. However, this requires that tightened standards be fulfilled. Among them is the microbiological safety of reused water. Although chlorination is the mostly applied disinfection system, it presents several disadvantages, such as the high doses required and the possibility of formation of dangerous by-products. Moreover, the threat of antibiotic resistance genes (ARGs) spread throughout poorly treated water is requiring the implementation of more efficient disinfection systems. Ozone and photo assisted disinfection technologies are being given special attention to reach treated water with higher quality. Still, much must be done to optimize the processes so that cost-effective systems may be obtained. This review paper gives a critical overview on the application of ozone and photo-based disinfection systems, bearing in mind their advantages and disadvantages when applied to water and municipal wastewater. Also, the possibility of integrated disinfection systems is considered.
Metal-Catalyzed and Metal-Mediated Approaches to the Synthesis and Functionalization of Tetramic Acids
Authors: Matiadis Dimitris
Published: January 2019

The heterocyclic ring of tetramic acids is found in naturally occurred biologically active products isolated from fungi, bacteria, molds, and sponges. Thus, these molecules have attracted significant attention as synthetic targets, and various synthetic paths have been developed. Over recent years, a growing number of catalytic approaches toward functionalized products have been established in order to overcome the limitations of the conventional methods. The present review describes the strategies for the metal-catalyzed and metal-promoted synthesis and further derivatization of tetramic acids, with emphasis on recent examples from the literature.
Altering Conversion and Product Selectivity of Dry Reforming of Methane in a Dielectric Barrier Discharge by Changing the Dielectric Packing Material
Authors: Michielsen Inne , Uytdenhouwen Yannick , Bogaerts Annemie , Meynen Vera
Published: January 2019

We studied the influence of dense, spherical packing materials, with different chemical compositions, on the dry reforming of methane (DRM) in a dielectric barrier discharge (DBD) reactor. Although not catalytically activated, a vast effect on the conversion and product selectivity could already be observed, an influence which is often neglected when catalytically activated plasma packing materials are being studied. The α-Al2O3 packing material of 2.0–2.24 mm size yields the highest total conversion (28%), as well as CO2 (23%) and CH4 (33%) conversion and a high product fraction towards CO (~70%) and ethane (~14%), together with an enhanced CO/H2 ratio of 9 in a 4.5 mm gap DBD at 60 W and 23 kHz. γ-Al2O3 is only slightly less active in total conversion (22%) but is even more selective in products formed than α-Al2O3. BaTiO3 produces substantially more oxygenated products than the other packing materials but is the least selective in product fractions and has a clear negative impact on CO2 conversion upon addition of CH4. Interestingly, when comparing to pure CO2 splitting and when evaluating differences in products formed, significantly different trends are obtained for the packing materials, indicating a complex impact of the presence of CH4 and the specific nature of the packing materials on the DRM process.
Recent Advances in Acyl Suzuki Cross-Coupling
Authors: Buchspies Jonathan , Szostak Michal
Published: January 2019

Acyl Suzuki cross-coupling involves the coupling of an organoboron reagent with an acyl electrophile (acyl halide, anhydride, ester, amide). This review provides a timely overview of the very important advances that have recently taken place in the acylative Suzuki cross-coupling. Particular emphasis is directed toward the type of acyl electrophiles, catalyst systems and new cross-coupling partners. This review will be of value to synthetic chemists involved in this rapidly developing field of Suzuki cross-coupling as well as those interested in using acylative Suzuki cross-coupling for the synthesis of ketones as a catalytic alternative to stoichiometric nucleophilic additions or Friedel-Crafts reactions.
Enzymatic Synthesis of ω-Hydroxydodecanoic Acid By Employing a Cytochrome P450 from Limnobacter sp. 105 MED
Authors: Joo Sung-Yeon , Yoo Hee-Wang , Sarak Sharad , Kim Byung-Gee , Yun Hyungdon
Published: January 2019

ω-Hydroxylated fatty acids are valuable and versatile building blocks for the production of various adhesives, lubricants, cosmetic intermediates, etc. The biosynthesis of ω-hydroxydodecanoic acid from vegetable oils is one of the important green pathways for their chemical-based synthesis. In the present study, the novel monooxygenase CYP153AL.m from Limnobacter sp. 105 MED was used for the whole-cell biotransformations. We constructed three-component system that was comprised of CYP153AL.m, putidaredoxin and putidaredoxin reductase from Pseudomonas putida. This in vivo study demonstrated that CYP153AL.m is a powerful catalyst for the biosynthesis of ω-hydroxydodecanoic acid. Under optimized conditions, the application of a solid-state powdered substrate rather than a substrate dissolved in DMSO significantly enhanced the overall reaction titer of the process. By employing this efficient system, 2 g/L of 12-hydroxydodecanoic acid (12-OHDDA) was produced from 4 g/L of its corresponding fatty acid, which was namely dodecanoic acid. Furthermore, the system was extended to produce 3.28 g/L of 12-OHDDA using 4 g/L of substrate by introducing native redox partners. These results demonstrate the utility of CYP153AL.m-catalyzed biotransformations in the industrial production of 12-OHDDA and other valuable building blocks.
Synthesis, Characterization and CO Tolerance Evaluation in PEMFCs of Pt2RuMo Electrocatalysts
Authors: González-Hernández Martin , Antolini Ermete , Perez Joelma
Published: January 2019

Pt2RuMo/C catalysts were synthesized by the modified polyol method in the presence and absence of Li(C2H5)3BH (LBH), annealed at 600 °C under H2 atmosphere to improve the reduction of Pt and Ru to provide stronger interactions between Mo and another metals. LBH affected the physico-chemical characteristics of Pt2RuMo, that is, in the presence of LBH an increment of Mo(IV) amount and a decrease in the PtRu alloying degree were observed. The catalytic activity for hydrogen oxidation in the presence and absence of CO (CO tolerance) of the Pt2RuMo/C catalysts as anodes in polymer electrolyte membrane fuel cells (PEMFCs) was compared to that of a commercial PtRu/C catalyst. The results indicated that the CO tolerance increased with an increase in Mo(IV) content, but the stability increased with an increment of the amount of Ru oxides in the catalysts.
Review of Anodic Catalysts for SO2 Depolarized Electrolysis for “Green Hydrogen” Production
Authors: Díaz-Abad Sergio , Millán María , Rodrigo Manuel A. , Lobato Justo
Published: January 2019

In the near future, primary energy from fossil fuels should be gradually replaced with renewable and clean energy sources. To succeed in this goal, hydrogen has proven to be a very suitable energy carrier, because it can be easily produced by water electrolysis using renewable energy sources. After storage, it can be fed to a fuel cell, again producing electricity. There are many ways to improve the efficiency of this process, some of them based on the combination of the electrolytic process with other non-electrochemical processes. One of the most promising is the thermochemical hybrid sulphur cycle (also known as Westinghouse cycle). This cycle combines a thermochemical step (H2SO4 decomposition) with an electrochemical one, where the hydrogen is produced from the oxidation of SO2 and H2O (SO2 depolarization electrolysis, carried out at a considerably lower cell voltage compared to conventional electrolysis). This review summarizes the different catalysts that have been tested for the oxidation of SO2 in the anode of the electrolysis cell. Their advantages and disadvantages, the effect of platinum (Pt) loading, and new tendencies in their use are presented. This is expected to shed light on future development of new catalysts for this interesting process.
Exploration of Light-Controlled Chemical Behavior and Mechanism in a Macrocyclic Copper Complex Catalyst–Acetone–Glucose–Bromate–Sulfuric Acid Oscillation System
Authors: Hu Lin , Cui Qujin , Zhang Yaqin , Zhou Xiaoqin , Pan Yatin , Tang Juan , Li Jinqing , Xu Wenyuan , Xu Hanhong
Published: January 2019

In this paper, the effect of ultraviolet light on the [CuL](ClO4)2–glucose (Glu)–acetone (Act)–sodium bromate (NaBrO3)–sulfuric acid (H2SO4) oscillation system was studied. The reaction mechanism and Oregonator model were established to verify the mechanism. Comparison of the bromide ion electrode–platinum electrode correlation diagrams with and without ultraviolet light reveals a nontracking phenomenon in the bromide ion electrode–platinum electrode correlation diagram under illumination, indicating that the illumination will affect the changes in the bromide ion concentration in the system. During the process, as UV intensity increases, the concentration of bromide ions in the system increases, and bromide ions can inhibit chemical oscillations, resulting in a decrease in the amplitude of chemical oscillations, further verifying that the proposed mechanism is reasonable.
Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles
Authors: Serejo Teresa Raquel Tavares , Silva-Carvalho Amandda Évelin , Braga Luma Dayane de Carvalho Filiú , Neves Francisco de Assis Rocha , Pereira Rinaldo Wellerson , Carvalho Juliana Lott de , Saldanha-Araujo Felipe
Published: January 2019

There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in order to avoid the complexity of a cellular therapy. Here, we investigate the effects of human adipose MSCs (AMSCs) licensing with INF-γ and TLR3 agonist over AMSCs proliferation, migration, as well as the immunomodulatory function. Furthermore, we evaluated how the licensing of AMSCs affected the immunomodulatory function of AMSC derived-secretome, including their EVs. INF-γ licensed-AMSCs presented an elevated expression of indoleamine 2,3-dioxygenase (IDO), accompanied by increased ICAM-1, as well as a higher immunosuppressive potential, compared to unlicensed AMSCs. Interestingly, the conditioned medium obtained from INF-γ licensed-AMSCs also revealed a slightly superior immunosuppressive potential, compared to other licensing strategies. Therefore, unlicensed and INF-γ licensed-AMSCs groups were used to isolate EVs. Interestingly, EVs isolated from both groups displayed similar capacity to inhibit T-cell proliferation. EVs isolated from both groups shared similar TGF-β and Galectin-1 mRNA content but only EVs derived from INF-γ licensed-AMSCs expressed IDO mRNA. In summary, we demonstrated that INF-γ licensing of AMSCs provides an immunosuppressive advantage both from a cell-cell contact-dependent perspective, as well as in a cell-free context. Interestingly, EVs derived from unlicensed and INF-γ licensed-AMSCs have similar ability to control activated T-cell proliferation. These results contribute towards the development of new strategies to control the immune response based on AMSCs or their derived products.
Commonly Used Pancreatic Stellate Cell Cultures Differ Phenotypically and in Their Interactions with Pancreatic Cancer Cells
Authors: Lenggenhager Daniela , Amrutkar Manoj , Sántha Petra , Aasrum Monica , Löhr Johannes-Matthias , Gladhaug Ivar P. , Verbeke Caroline S.
Published: January 2019

Activated pancreatic stellate cells (PSCs) play a central role in the tumor stroma of pancreatic ductal adenocarcinoma (PDAC). Given the limited availability of patient-derived PSCs from PDAC, immortalized PSC cell lines of murine and human origin have been established; however, it is not elucidated whether differences in species, organ disease status, donor age, and immortalization alter the PSC phenotype and behavior compared to that of patient-derived primary PSC cultures. Therefore, a panel of commonly used PSC cultures was examined for important phenotypical and functional features: three primary cultures from human PDAC, one primary from normal human pancreas, and three immortalized (one from human, two from murine pancreas). Growth rate was considerably lower in primary PSCs from human PDAC. Basal collagen synthesis varied between the PSC cultures, and TGF-β stimulation increased collagen synthesis only in non-immortalized cultures. Differences in secretome composition were observed along with a divergence in the DNA synthesis, migration, and response to gemcitabine of PDAC cell lines that were grown in conditioned medium from the various PSC cultures. The findings reveal considerable differences in features and functions that are key to PSCs and in the interactions with PDAC. These observations may be relevant to researchers when selecting the most appropriate PSC culture for their experiments.
Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action
Authors: Behrangi Newshan , Fischbach Felix , Kipp Markus
Published: January 2019

Multiple sclerosis (MS) is a neuroinflammatory disorder of the central nervous system (CNS), and represents one of the main causes of disability in young adults. On the histopathological level, the disease is characterized by inflammatory demyelination and diffuse neurodegeneration. Although on the surface the development of new inflammatory CNS lesions in MS may appear consistent with a primary recruitment of peripheral immune cells, questions have been raised as to whether lymphocyte and/or monocyte invasion into the brain are really at the root of inflammatory lesion development. In this review article, we discuss a less appreciated inflammation-neurodegeneration interplay, that is: Neurodegeneration can trigger the formation of new, focal inflammatory lesions. We summarize old and recent findings suggesting that new inflammatory lesions develop at sites of focal or diffuse degenerative processes within the CNS. Such a concept is discussed in the context of the EXPAND trial, showing that siponimod exerts anti-inflammatory and neuroprotective activities in secondary progressive MS patients. The verification or rejection of such a concept is vital for the development of new therapeutic strategies for progressive MS.
Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies
Authors: Lang Liwei , Teng Yong
Published: January 2019

Fibroblast growth factor receptor 4 (FGFR4), a tyrosine kinase receptor for FGFs, is involved in diverse cellular processes, including the regulation of cell proliferation, differentiation, migration, metabolism, and bile acid biosynthesis. High activation of FGFR4 is strongly associated with the amplification of its specific ligand FGF19 in many types of solid tumors and hematologic malignancies, where it acts as an oncogene driving the cancer development and progression. Currently, the development and therapeutic evaluation of FGFR4-specific inhibitors, such as BLU9931 and H3B-6527, in animal models and cancer patients, are paving the way to suppress hyperactive FGFR4 signaling in cancer. This comprehensive review not only covers the recent discoveries in understanding FGFR4 regulation and function in cancer, but also reveals the therapeutic implications and applications regarding emerging anti-FGFR4 agents. Our aim is to pinpoint the potential of FGFR4 as a therapeutic target and identify new avenues for advancing future research in the field.
A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis
Authors: Nishimi Shinichiro , Isozaki Takeo , Wakabayashi Kuninobu , Takeuchi Hiroko , Kasama Tsuyoshi
Published: January 2019

A disintegrin and metalloprotease 15 (ADAM15) is involved in several malignancies. In this study, we investigated the role of ADAM15 in rheumatoid arthritis (RA) angiogenesis. Soluble ADAM15 (s-ADAM15) in serum from RA and normal (NL) subjects was measured using ELISA. To determine membrane-anchored ADAM15 (ADAM15) expression in RA synovial tissues, immunohistochemistry was performed. To examine the role of ADAM15 in angiogenesis, we performed in vitro Matrigel assays and monocyte adhesion assays using human umbilical vein endothelial cells (HUVECs) transfected with ADAM15 siRNA. Finally, to investigate whether angiogenic mediators were affected by ADAM15, cytokines in ADAM15 siRNA-transfected HUVEC-conditioned medium were measured. ADAM15 was significantly higher in RA serum than in NL serum. ADAM15 was also expressed on RAST endothelial cells. ADAM15 siRNA-treated HUVECs had decreased EC tube formation in response to RA synovial fluids compared with non-treated HUVECs. The adhesion index of ADAM15 siRNA-transfected HUVECs was significantly lower than the adhesion index of control siRNA-transfected HUVECs. ENA-78/CXCL5 and ICAM-1 were decreased in tumor necrosis factor (TNF)-α-stimulated ADAM15 siRNA-transfected HUVEC-conditioned medium compared with TNF-α-stimulated control siRNA-transfected HUVEC-conditioned medium. These data show that ADAM15 plays a role in RA angiogenesis, suggesting that ADAM15 might be a potential target in inflammatory diseases such as RA.
Crohn’s Disease-Associated Adherent-Invasive Escherichia coli Manipulate Host Autophagy by Impairing SUMOylation
Authors: Dalmasso Guillaume , Nguyen Hang T. T. , Faïs Tiphanie , Massier Sébastien , Barnich Nicolas , Delmas Julien , Bonnet Richard
Published: January 2019

The intestinal mucosa of Crohn’s disease (CD) patients is abnormally colonized with adherent-invasive Escherichia coli (AIEC) that are able to adhere to and to invade intestinal epithelial cells (IECs), to survive in macrophages, and to induce a pro-inflammatory response. AIEC persist in the intestine, and induce inflammation in CEABAC10 transgenic mice expressing human CAECAM6, the receptor for AIEC. SUMOylation is a eukaryotic-reversible post-translational modification, in which SUMO, an ubiquitin-like polypeptide, is covalently linked to target proteins. Here, we investigated the role of SUMOylation in host responses to AIEC infection. We found that infection with the AIEC LF82 reference strain markedly decreased the levels of SUMO-conjugated proteins in human intestinal epithelial T84 cells. This was also observed in IECs from LF82-infected CEABAC10 transgenic mice. LF82-induced deSUMOylation in IECs was due in part to increased level of microRNA (miR)-18, which targets PIAS3 mRNA encoding a protein involved in SUMOylation. Over-expression of SUMOs in T84 cells induced autophagy, leading to a significant decrease in the number of intracellular LF82. Consistently, a decreased expression of UBC9, a protein necessary for SUMOylation, was accompanied with a decrease of LF82-induced autophagy, increasing bacterial intracellular proliferation and inflammation. Finally, the inhibition of miR-18 significantly decreased the number of intracellular LF82. In conclusion, our results suggest that AIEC inhibits the autophagy response to replicate intracellularly by manipulating host SUMOylation.
Aberrant hiPSCs-Derived from Human Keratinocytes Differentiates into 3D Retinal Organoids that Acquire Mature Photoreceptors
Authors: Shrestha Rupendra , Wen Yao-Tseng , Ding Dah-Ching , Tsai Rong-Kung
Published: January 2019

Human induced pluripotent stem cell (hiPSC)-derived three-dimensional retinal organoids are a new platform for studying the organoidogenesis. However, recurrent genomic aberration, acquired during generation of hiPSCs, limit its biomedical application and/or aberrant hiPSCs has not been evaluated for generation of differentiated derivatives, such as organoids and retinal pigment epithelium (RPE). In this study, we efficiently differentiated mosaic hiPSCs into retinal organoids containing mature photoreceptors. The feeder-free hiPSCs were generated from the human epidermal keratinocytes that were rapid in process with improved efficiency over several passages and maintained pluripotency. But, hiPSCs were cytogenetically mosaic with normal and abnormal karyotypes, while copy number variation analysis revealed the loss of chromosome 8q. Despite this abnormality, the stepwise differentiation of hiPSCs to form retinal organoids was autonomous and led to neuronal lamination. Furthermore, the use of a Notch inhibitor, DAPT, at an early timepoint from days 29–42 of culture improved the specification of the retinal neuron and the use of retinoic acid at days 70–120 led to the maturation of photoreceptors. hiPSC-derived retinal organoids acquired all subtypes of photoreceptors, such as RHODOPSIN, B-OPSIN and R/G-OPSIN. Additionally, the advanced maturation of photoreceptors was observed, revealing the development of specific sensory cilia and the formation of the outer-segment disc. This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.
Forest Tree Microbiomes and Associated Fungal Endophytes: Functional Roles and Impact on Forest Health
Authors: Terhonen Eeva , Blumenstein Kathrin , Kovalchuk Andriy , Asiegbu Fred O.
Published: January 2019

Terrestrial plants including forest trees are generally known to live in close association with microbial organisms. The inherent features of this close association can be commensalism, parasitism or mutualism. The term “microbiota” has been used to describe this ecological community of plant-associated pathogenic, mutualistic, endophytic and commensal microorganisms. Many of these microbiota inhabiting forest trees could have a potential impact on the health of, and disease progression in, forest biomes. Comparatively, studies on forest tree microbiomes and their roles in mutualism and disease lag far behind parallel work on crop and human microbiome projects. Very recently, our understanding of plant and tree microbiomes has been enriched due to novel technological advances using metabarcoding, metagenomics, metatranscriptomics and metaproteomics approaches. In addition, the availability of massive DNA databases (e.g., NCBI (USA), EMBL (Europe), DDBJ (Japan), UNITE (Estonia)) as well as powerful computational and bioinformatics tools has helped to facilitate data mining by researchers across diverse disciplines. Available data demonstrate that plant phyllosphere bacterial communities are dominated by members of only a few phyla (Proteobacteria, Actinobacteria, Bacteroidetes). In bulk forest soil, the dominant fungal group is Basidiomycota, whereas Ascomycota is the most prevalent group within plant tissues. The current challenge, however, is how to harness and link the acquired knowledge on microbiomes for translational forest management. Among tree-associated microorganisms, endophytic fungal biota are attracting a lot of attention for their beneficial health- and growth-promoting effects, and were preferentially discussed in this review.
Decreasing the Fuel Consumption and CO2 Emissions of Excavator-Based Harvesters with a Machine Control System
Authors: Spinelli Raffaele , De Arruda Moura Angelo Conrado
Published: January 2019

Compared with purpose-built units, excavator-based harvesters offer many advantages, but they also face one main limitation: a much higher fuel consumption, which also results in higher CO2 emission levels. The fuel efficiency of excavator-based harvesters can be increased by a better interface between the excavator and the harvester head. This study aimed to determine the performance of a new adaptation kit, specifically designed to improve the communication between these two components. The new kit offers real-time adjustment between the power demand of the harvester head and the power output of the excavator, which should help reducing fuel consumption while stabilizing hydraulic fluid temperature. The test was conducted on 53 excavator-based harvesters purchased and managed by a large Brazilian company. Time use, fuel consumption and production were monitored continuously for one full month, before and after installation of the kit. Overall, the study covered 40,000 h of work, during which the harvesters cut, processed, and debarked 4.5 million trees, or 650,000 m3 of wood, under bark. Fuel consumption amounted to 900,000 liters. After installing the adaptation kit, productivity increased 6%, while fuel consumption per hour decreased 3.5%. Fuel consumption and CO2 emissions per product unit decreased 10%, as an average. The effect of random variability typical of an observational study prevented formulating an accurate figure for the amount of fuel that can be saved by installing the adaptation kit. Yet, one may confidently state that, in most cases, installing the kit results in a reduction of fuel use, and that such reduction is most often in the range from −10 to −20% on a per m3 basis.
On the Steady-State Flow and Yielding Behaviour of Lubricating Greases
Authors: Delgado Miguel A. , Secouard Sebastien , Valencia Concepción , Franco José M.
Published: January 2019

Practical steady-state flow curves were obtained from different rheological tests and protocols for five lubricating greases, containing thickeners of a rather different nature, i.e., aluminum complex, lithium, lithium complex, and calcium complex soaps and polyurea. The experimental results demonstrated the difficulty to reach “real” steady-state flow conditions for these colloidal suspensions as a consequence of the strong time dependence and marked yielding behavior in a wide range of shear rates, resulting in flow instabilities such as shear banding and fracture. In order to better understand these phenomena, transient flow experiments, at constant shear rates, and creep tests, at constant shear stresses, were also carried out using controlled-strain and controlled-stress rheometers, respectively. The main objective of this work was to study the steady-state flow behaviour of lubricating greases, analyzing how the microstructural characteristics may affect the yielding flow behaviour.
Acknowledgement to Reviewers of Gels in 2018
Authors:   Gels Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing[...]
Epigenetic Biomarkers in Cell-Free DNA and Applications in Liquid Biopsy
Authors: Gai Wanxia , Sun Kun
Published: January 2019

Cell-free circulating DNA (cfDNA) in plasma has gained global interest as a diagnostic material for noninvasive prenatal testing and cancer diagnosis, or the so-called “liquid biopsy”. Recent studies have discovered a great number of valuable genetic and epigenetic biomarkers for cfDNA-based liquid biopsy. Considering that the genetic biomarkers, e.g., somatic mutations, usually vary from case to case in most cancer patients, epigenetic biomarkers that are generalizable across various samples thus possess certain advantages. In this study, we reviewed the most recent studies and advances on utilizing epigenetic biomarkers for liquid biopsies. We first reviewed more traditional methods of using tissue/cancer-specific DNA methylation biomarkers and digital PCR or sequencing technologies for cancer diagnosis, as well as tumor origin determination. In the second part, we discussed the emerging novel approaches for exploring the biological basis and clinical applications of cfDNA fragmentation patterns. We further provided our comments and points of view on the future directions on epigenetic biomarker development for cfDNA-based liquid biopsies.