bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Applied during Deep Friction Massage: Characterization and Relationship with Time of Onset of Analgesia
Authors: Chaves Paula , Simões Daniela , Paço Maria , Pinho Francisco , Duarte José Alberto , Ribeiro Fernando
Published: April 2020

This study aims to determine if a dose–response relationship exists between the pressure applied during deep friction massage (DFM) and the time to the onset of analgesia in an asymptomatic patellar tendon. For this purpose, pressures applied by physiotherapists during DFM (study 1) were characterized and then, based on these pressures, the effects of different DFM pressures on the time to the onset of analgesia were assessed (study 2). First, the mean pressure applied by 40 physiotherapists during a DFM session was assessed with a pressure sensor through an observational, cross-sectional and analytical study. Next, the effects of different pressure intensities (the median, the percentile 25 (P25), and the percentile 75 (P75) of the mean pressure obtained in study 1) were studied in a crossover trial enrolling 30 participants with an asymptomatic patellar tendon. A pressure sensor was used to register the pressures applied during DFM. Our main results indicated that the physiotherapists applied pressures with a wide variation ((mean pressure: 2.317 kg/cm2 (P25: 1.022 kg/cm2; P75: 4.161 kg/cm2)). It was also shown that higher pressures had shorter times to the onset of analgesia (pressure: 1 kg/m2, time to the onset of analgesia: 67.0 s (P25: 84.5 s; P75: 113.5 s); pressure: 2.3 kg/m2, time to the onset of analgesia: 59.0 s (P25: 73.5 s; P75: 87.3 s); pressure: 4.2 kg/m2, time to the onset of analgesia: 37.8 s (P25: 54.0 s; P75: 62.0 s)) (p ≤ 0.001). In conclusion, the mean DFM pressure obtained by the physiotherapists was 2.3 kg/cm2 (P25: 1.02 kg/cm2; P75: 4.16 kg/cm2). Higher pressures of DFM resulted in shorter times to the onset of analgesia.
Efficiency of Five Selected Aquatic Plants in Phytoremediation of Aquaculture Wastewater
Authors: Mohd Nizam Nurul Umairah , Mohd Hanafiah Marlia , Mohd Noor Izzati , Abd Karim Hazwani Izzati
Published: April 2020

The lack of clean water sources, due to the presence of pollutants in water, is a major issue in many countries, including Malaysia. To overcome this problem, various methods have been introduced, including phytoremediation treatment. Therefore, this phytoremediation study examined the ability of five aquatic plants—Centella asiatica, Ipomoea aquatica, Salvinia molesta, Eichhornia crassipes, and Pistia stratiotes—to remove three pollutants—total suspended solids (TSS), ammoniacal nitrogen (NH3-N), and phosphate—from aquaculture wastewater. Using wastewater samples, each containing 50 g of one of the plants, the pollutant levels were measured every two days for 14 days. The results showed a drastic decline in the concentration of pollutants, where C. asiatica was able to remove 98% of NH3-N, 90% of TSS, and 64% of phosphate, while I. aquatica showed the potential to eliminate up to 73% of TSS and NH3-N, and 50% of phosphate. E. crassipes drastically removed 98% of phosphate, 96% of TSS, and 74% of NH3-N, while P. stratiotes was able to eliminate 98% of TSS, 78% of NH3-N, and 89% of phosphate. S. molesta was efficient in removing 89.3% of TSS and 88.6% of phosphate, but only removed 63.9% of NH3-N.
Women Architects in the Transition: Comparative Analysis of ‘Palomeras’ Dwellings, Madrid (Spain)
Authors: Cordero Ampuero Angel
Published: April 2020

This study examines the contribution of women architects to Palomeras operation projects in the context of the Spanish transition and the Madrid housing emergency in the late 1970s and early 1980s. Works were selected according to their professional impacts; 11 projects were analyzed by redrawing and studying the main types of dwelling. The current reading interpretation—according to a gender perspective—focuses on reproduction of tasks in main spaces at home: in-depth testing of the scope of kitchen surface and glazing ratios, as well as direct lighting, views and minimum distance of housekeeping paths. Furthermore, the comparative and qualitative analysis was based on meaningful data, which yield subtle but expressive results about the consequences of gender-inclusive architect teams. Thus, it is possible to approach and discuss the role played by some women architects of the Madrid School after second-wave feminism, in a key time for gender change in architectural practice in Spain.
Variables Reduction in Sequential Resource Allocation Problems
Authors: Hinz Juri , Vargiolu Tiziano
Published: April 2020

This paper presents a general framework to address diverse notoriously difficult problems arising in the area of optimal resource management, exploitation of natural reserves, pension fund valuation, environmental protection, and storage operation. Using some common abstract features of this problem class, we present a technique which provides a significant reduction of decision variables. As an application, we discuss a battery storage control to show how a decision problem, which is practically unsolvable in the original formulation, can be treated by our method.
Numerical Simulation of Haze-Fog Particle Dispersion in the Typical Urban Community by Using Discrete Phase Model
Authors: Zhu Hongbo , Su Jie , Wei Xuesen , Han Zhaolong , Zhou Dai , Wang Xun , Bao Yan
Published: April 2020

The haze-fog particle dispersion in urban communities will cause serious health and environmental problems, which has aroused society attention. The aim of the present investigation is to reveal the underlying mechanisms of haze-fog particle dispersion via Computational Fluid Dynamics (CFD) method, and then to provide a groundwork for the optimal spatial arrangement of urban architecture. The Delayed Detached-eddy Simulation turbulence model (DDES) and Discrete Phase Model (DPM) are utilized to investigate the wind flow distribution and the particle dispersion around the building group. The numerical results show that the particle dispersion is dominated by the incoming wind flow, the layout of architectural space and the type and distribution of vortex. The ‘single body’ wake pattern and the vortex impingement wake pattern are identified in the wind flow field, which have different effects on the distribution of haze-fog particle. The cavity formed by the layout of the building group induces primary vortex and secondary vortex, which will make it more difficult for the particles entering the square cavity to flow out. Moreover, the concentration of the particle in the rear of the buildings is relatively low due the effect of attached vortices.
Sensitivity of a Bowing Mesoscale Convective System to Horizontal Grid Spacing in a Convection-Allowing Ensemble
Authors: Lawson John R. , Gallus William A. , Potvin Corey K.
Published: April 2020

The bow echo, a mesoscale convective system (MCS) responsible for much hail and wind damage across the United States, is associated with poor skill in convection-allowing numerical model forecasts. Given the decrease in convection-allowing grid spacings within many operational forecasting systems, we investigate the effect of finer resolution on the character of bowing-MCS development in a real-data numerical simulation. Two ensembles were generated: one with a single domain of 3-km horizontal grid spacing, and another nesting a 1-km domain with two-way feedback. Ensemble members were generated from their control member with a stochastic kinetic-energy backscatter scheme, with identical initial and lateral-boundary conditions. Results suggest that resolution reduces hindcast skill of this MCS, as measured with an adaptation of the object-based Structure–Amplitude–Location method. The nested 1-km ensemble produces a faster system than in both the 3-km ensemble and observations. The nested 1-km simulation also produced stronger cold pools, which could be enhanced by the increased (fractal) cloud surface area with higher resolution, allowing more entrainment of dry air and hence increased evaporative cooling.
Statistical Analysis of Turbulence Characteristics over the Tropical Western Pacific Based on Radiosonde Data
Authors: He Yang , Sheng Zheng , Zhou Lesong , He Mingyuan , Zhou Shudao
Published: April 2020

The tropical region is a key area for the interaction between the stratosphere and troposphere. The strong convective activity in the troposphere produces a series of gravity wave activities, which result in strong and widespread turbulence over the region. Therefore, studying the turbulent activity in the western Pacific is essential for understanding the characteristics of atmospheric disturbance over this region, which has the world’s most complex circulation system. In this paper, we explore the characteristics of atmospheric turbulence distribution over Guam in this region, and the Thorpe sorting method is used to study one-second resolution radiosonde data from the US. On the basis of the background field and local instability, the turbulence generation mechanism is discussed in detail. Results show that the US high-resolution balloon data are efficacious for tropospheric turbulence retrieval but increasingly affected by instrument noise as altitude increases. It is also found that there is a strong turbulent mixing band caused by both shear instability and static instability near the tropopause, where the turbulence activity is markedly enhanced and characterized by annual oscillation, reaching the maximum from July to September.
Possible Increase of Vegetation Exposure to Spring Frost under Climate Change in Switzerland
Authors: Lhotka Ondřej , Brönnimann Stefan
Published: April 2020

We assessed future changes in spring frost risk for the Aare river catchment that comprises the Swiss Plateau, the most important agricultural region of Switzerland. An ensemble of 15 bias-corrected regional climate model (RCM) simulations from the EXAR data set forced by the RCP 4.5 and RCP 8.5 concentration pathways were analysed for two future periods. Correlating actual meteorological observations and Swiss phenological spring index, we proposed and tested an RCM-compatible methodology (based on temperature data only) for estimating a start of spring and severity of frost events. In the historical climate, a significant advancement in start of spring was observed and frost events were more frequent in those years in which spring started sooner. In 2021–2050, spring is projected to start eight (twelve) days earlier, considering the RCP 4.5 (8.5) scenario. Substantial changes were simulated for the 2070–2099 period under RCP 8.5, when the total severity of frost events was projected to be increased by a factor of 2.1 compared to the historical climate. The study revealed the possible future increase of vegetation exposure to spring frost in Switzerland and that this phenomenon is noticeable even in the near future under the ‘low concentration’ RCP 4.5 scenario.
Theoretical Impact of Manufacturing Tolerance on Lithium-Ion Electrode and Cell Physical Properties
Authors: Yourey William
Published: April 2020

The range of electrode porosity, electrode internal void volume, cell capacity, and capacity ratio that result from electrode coating and calendering tolerance can play a considerable role in cell-to-cell and lot-to-lot performance variation. Based on a coating loading tolerance of ±0.4 mg/cm2 and calender tolerance of ±3.0 μm, the resulting theoretical range of physical properties was investigated. For a target positive electrode porosity of 30%, the resulting porosity can range from 19.6% to 38.6%. To account for this variation during the manufacturing process, as much as 41% excess or as little as 59% of the target electrolyte quantity should be added to cells to match the positive electrode void volume. Similar results are reported for a negative electrode of 40% target porosity, where a range from 30.8% to 48.0% porosity is possible. For the negative electrode as little as 72% up to 28% excess electrolyte should be added to fill the internal void space. Although the results are specific to each electrode composition, density, chemistry, and loading the presented process highlight the possible variability of the produced parts. These results are further magnified as cell design moves toward higher power applications with thinner electrode coatings.
Nicotinamide, Nicotinamide Riboside and Nicotinic Acid—Emerging Roles in Replicative and Chronological Aging in Yeast
Authors: Orlandi Ivan , Alberghina Lilia , Vai Marina
Published: April 2020

Nicotinamide, nicotinic acid and nicotinamide riboside are vitamin B3 precursors of NAD+ in the human diet. NAD+ has a fundamental importance for cellular biology, that derives from its essential role as a cofactor of various metabolic redox reactions, as well as an obligate co-substrate for NAD+-consuming enzymes which are involved in many fundamental cellular processes including aging/longevity. During aging, a systemic decrease in NAD+ levels takes place, exposing the organism to the risk of a progressive inefficiency of those processes in which NAD+ is required and, consequently, contributing to the age-associated physiological/functional decline. In this context, dietary supplementation with NAD+ precursors is considered a promising strategy to prevent NAD+ decrease and attenuate in such a way several metabolic defects common to the aging process. The metabolism of NAD+ precursors and its impact on cell longevity have benefited greatly from studies performed in the yeast Saccharomyces cerevisiae, which is one of the most established model systems used to study the aging processes of both proliferating (replicative aging) and non-proliferating cells (chronological aging). In this review we summarize important aspects of the role played by nicotinamide, nicotinic acid and nicotinamide riboside in NAD+ metabolism and how each of these NAD+ precursors contribute to the different aspects that influence both replicative and chronological aging. Taken as a whole, the findings provided by the studies carried out in S. cerevisiae are informative for the understanding of the complex dynamic flexibility of NAD+ metabolism, which is essential for the maintenance of cellular fitness and for the development of dietary supplements based on NAD+ precursors.
Sorafenib as an Inhibitor of RUVBL2
Authors: Nano Nardin , Ugwu Francisca , Seraphim Thiago V. , Li Tangzhi , Azer Gina , Isaac Methvin , Prakesch Michael , Barbosa Leandro R. S. , Ramos Carlos H. I. , Datti Alessandro , Houry Walid A.
Published: April 2020

RUVBL1 and RUVBL2 are highly conserved ATPases that belong to the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various complexes and cellular processes, several of which are closely linked to oncogenesis. The proteins were implicated in DNA damage signaling and repair, chromatin remodeling, telomerase activity, and in modulating the transcriptional activities of proto-oncogenes such as c-Myc and β-catenin. Moreover, both proteins were found to be overexpressed in several different types of cancers such as breast, lung, kidney, bladder, and leukemia. Given their various roles and strong involvement in carcinogenesis, the RUVBL proteins are considered to be novel targets for the discovery and development of therapeutic cancer drugs. Here, we describe the identification of sorafenib as a novel inhibitor of the ATPase activity of human RUVBL2. Enzyme kinetics and surface plasmon resonance experiments revealed that sorafenib is a weak, mixed non-competitive inhibitor of the protein’s ATPase activity. Size exclusion chromatography and small angle X-ray scattering data indicated that the interaction of sorafenib with RUVBL2 does not cause a significant effect on the solution conformation of the protein; however, the data suggested that the effect of sorafenib on RUVBL2 activity is mediated by the insertion domain in the protein. Sorafenib also inhibited the ATPase activity of the RUVBL1/2 complex. Hence, we propose that sorafenib could be further optimized to be a potent inhibitor of the RUVBL proteins.
FTIR Spectroscopy Study of the Secondary Structure Changes in Human Serum Albumin and Trypsin under Neutral Salts
Authors: Usoltsev Dmitrii , Sitnikova Vera , Kajava Andrey , Uspenskaya Mayya
Published: April 2020

The effect of neutral salts on protein conformation was first analyzed by Hofmeister in 1888, however, even today this phenomenon is not completely understood. To clarify this effect, we studied changes in the secondary structure of two proteins: human serum albumin with predominantly α-helical structure and porcine pancreas β-trypsin with the typical β-structural arrangement in aqueous solutions of neutral salts (KSCN, KCl, (NH4)2SO4). The changes in the secondary structure were studied at 23 °C and 80 °C by using the second derivative deconvolution method of the IR spectra. Our results demonstrated that the ability of the salts to stabilize/destabilize these two proteins correlates with the Hofmeister series of ions. At the same time, some exceptions were also observed. The destabilization of the native structures of both α-helical albumin and β-structural trypsin upon interaction with neutral salts leads to the formation of intermolecular β-sheets typical for amyloid fibrils or amorphous aggregates. Thus, our quantitative FTIR-spectroscopy analysis allowed us to further clarify the mechanisms and complexity of the neutral salt actions on protein structures which may lead to strategies preventing unwelcome misfolding of proteins.
Electrochemical Immunosensor for Human IgE Using Ferrocene Self-Assembled Monolayers Modified ITO Electrode
Authors: Park Myungsang , Song Yesol , Kim Ki Jun , Oh Seung Jun , Ahn Jun Ki , Park Hun , Shin Hang-Beum , Kwon Seong Jung
Published: April 2020

The immunoglobulin E (IgE) level in serum is an important factor in the examination of allergy. Ferrocene (Fc)-modified self-assembled monolayers (SAMs) were placed on an indium tin oxide (ITO) electrode as a sensing layer for the detection of human IgE. The Fc moiety in the SAMs facilitated the electron transfer through the organic SAMs layer and electrocatalytic signal amplification. The electrochemical measurement was accomplished after the sandwich type immobilization of the receptor antibody, target human IgE, and enzyme conjugated secondary antibody. The enzyme product, p-aminophenol, was quantitatively analyzed by redox cycling via Fc. In addition, the electrochemical impedance spectroscopy (EIS) was investigated for the detection of IgE. The limit of detection (LOD), limit of quantification (LOQ), and dynamic range of the electrochemical sensor were 3 IU/mL, 10 IU/mL, and from 10 IU/mL to 100 IU/mL, respectively.
Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know
Authors: Boziki Marina Kleopatra , Kesidou Evangelia , Theotokis Paschalis , Mentis Alexios-Fotios A. , Karafoulidou Eleni , Melnikov Mikhail , Sviridova Anastasia , Rogovski Vladimir , Boyko Alexey , Grigoriadis Nikolaos
Published: April 2020

An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.
Personal Values Associated with Prosocial Decisions
Authors: Heilman Renata M. , Kusev Petko
Published: April 2020

Social situations require people to make complex decisions, sometimes involving different outcomes for the self and others. Considering the long-lasting interest scholars are showing in the topic of social decisions, the aim of the current article is to add to this research line by looking at personal values as possible factors associated with a preference for more self-maximizing or cooperative choices. In a general adult sample (N = 63), we used the Social Value Orientation (SVO) slider measure to investigate participants’ tendency towards prosocial or proself outcomes. We also administered a personal values questionnaire, measuring 19 basic values, organized in 4 higher-order values. Building on the theory of basic individual values, we expected self-transcendence to be positively associated with more prosocial orientations. Our main result confirmed that self-transcendence was positively correlated with SVO whereas no other higher-order values were associated with SVO. Our data also revealed that inequality aversion was the primary motivation of prosocials, and this result was unrelated to gender effects or the personal values under investigation.
Smoking Status and Well-Being of Underserved African American Older Adults
Authors: Bazargan Mohsen , Cobb Sharon , Castro Sandoval Jessica , Assari Shervin
Published: April 2020

Purpose: This study investigated the association between current and past cigarette smoking, with four domains of well-being, namely, physical quality of life, mental quality of life, depressive symptoms, and self-rated health status (SRH), among older African American adults who lived in economically impoverished areas of South Los Angles. Methods: This community-based cross-sectional study included a convenience sample of economically-disadvantaged African Americans adults (n = 740) who were 55 years old and older residing in South Los Angeles. We conducted in-depth face-to-face interviews to collect data on the socioeconomic status (level of education and fiscal pressures), demographic factors (age and gender), physical health (number of chronic medical conditions), smoking (never smokers (reference group), past smokers, and current smokers), and well-being (quality of life, depressive symptoms, and self-rated health). Linear regressions were used to analyze the data. Results: Over 21% reported that they are current smokers, compared with 31% who identified as former smokers. Almost 40% perceived the quality of their health status to be fair or poor. Compared with non-smokers, current cigarette smokers reported a worse physical quality of life, depressive symptoms, and self-rated health. Current smokers also reported a marginally worse mental quality of life. Past smoker status was inconsistently associated with worse well-being in some, but not all, indicators. The association between smoking status and worse well-being was independent of gender, socioeconomic status, and physical health status. Conclusion: Current smoking is associated with worse well-being of older African American adults in economically constrained urban settings. As the same pattern could not be found for former smokers, quitting smoking may be a strategy for economically-disadvantaged African American individuals to enhance their well-being. This provides additional support for programs that help African American individuals who are smokers to quit smoking, particularly in economically-disadvantaged urban areas.
Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer
Authors: Buttarelli Marianna , De Donato Marta , Raspaglio Giuseppina , Babini Gabriele , Ciucci Alessandra , Martinelli Enrica , Baccaro Pina , Pasciuto Tina , Fagotti Anna , Scambia Giovanni , Gallo Daniela
Published: April 2020

Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.
Aspartate-β-Hydroxylase: A Promising Target to Limit the Local Invasiveness of Colorectal Cancer
Authors: Benelli Roberto , Costa Delfina , Mastracci Luca , Grillo Federica , Olsen Mark Jon , Barboro Paola , Poggi Alessandro , Ferrari Nicoletta
Published: April 2020

Colorectal cancer’s (CRC) ability to invade local tissues and lymph nodes and generate distant metastases is the key for TNM classification. Aspartate-β-hydroxylase (ASPH), a transmembrane protein that catalyzes Notch receptors and ligand activation, is involved in tumor invasion. Because Notch is involved in gut homeostasis, it could be a target for CRC therapy. ASPH mRNA and protein expression, promoter methylation and gene copy numbers were evaluated using the TCGA and CPTAC human CRC datasets. Using digital pathology, ASPH was scored in the luminal area (LM), center tumor (CT) and invasive margin (IM) of 100 human CRCs. The effect of ASPH targeting on invasiveness and viability was tested by siRNA knockdown and small molecule inhibitors (SMI). Bioinformatics analysis showed increased expression of ASPH mRNA and protein in CRC, paired with a decreased methylation profile. ASPH genetic gain or amplification was frequent (56%), while deletion was rare (0.03%). Digital pathology analysis showed that ASPH exerted its pathological activity in the invasive margin of the tumor, affecting invasive front morphology, tumor budding and patients’ overall survival. In vitro, ASPH targeting by siRNA or SMI reduced cell invasion and growth and caused Notch-1 downregulation. This study demonstrates that ASPH targeting by specific inhibitors could improve CRC treatment strategies.
Involvement of MicroRNA-296 in the Inhibitory Effect of Epigallocatechin Gallate against the Migratory Properties of Anoikis-Resistant Nasopharyngeal Carcinoma Cells
Authors: Lin Chien-Hung , Wang Hsin-Hui , Chen Tsung-Hsien , Chiang Ming-Chang , Hung Peir-Haur , Chen Yann-Jang
Published: April 2020

Short noncoding endogenous RNAs, including microRNAs (miRNAs), are associated with the development and metastasis of multiple cancers. Epigallocatechin gallate (EGCG), the most active and abundant polyphenol in green tea, plays a crucial role in the modulation of miRNA expression, which is related to changes in cancer progression. In the present study, we explore whether EGCG exerts its suppressive effects on nasopharyngeal carcinoma (NPC) cells through miRNA regulation. The anoikis-resistant sphere-forming NPC cells grown under anchorage-independent conditions exhibit enhanced migratory properties, which were inhibited by EGCG treatment. The miR-296 level was lower in the anoikis-resistant cells than in the monolayer parental cells; however, miR-296 was significantly upregulated after EGCG treatment. We demonstrate that miR-296 is involved in the inhibitory effects of EGCG on the anoikis-resistant NPC cells through the downregulation of signal transducer and activator of transcription 3 (STAT3) activation. Our study is the first to demonstrate that EGCG inhibited the migratory properties of anoikis-resistant cells by modulating the expression of miRNA in NPC cells. Our results indicate the novel effects of EGCG on miRNA regulation to inhibit an invasive phenotype of NPC as well as the regulatory role of miR-296.
Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
Authors: Qin San-Hai , Lau Andy T. Y. , Liang Zhan-Ling , Tan Heng Wee , Ji Yan-Chen , Zhong Qiu-Hua , Zhao Xiao-Yun , Xu Yan-Ming
Published: April 2020

The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy.
The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses
Authors: Beltrán Hernández Irati , Angelier Mathieu L. , Del Buono D’Ondes Tommaso , Di Maggio Alessia , Yu Yingxin , Oliveira Sabrina
Published: April 2020

Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro- inflammatory cytokines IL- 1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.
Greener Synthesis of Nitrogen-Containing Heterocycles in Water, PEG, and Bio-Based Solvents
Authors: Campos Joana F. , Berteina-Raboin Sabine
Published: April 2020

The solvents used in chemistry are a fundamental element of the environmental performance of processes in corporate and academic laboratories. Their influence on costs, health safety, and nature cannot be neglected. Quantitatively, solvents are the most abundant constituents of chemical transformations; therefore, acting on solvents and replacing standard solvents with safer products can have a great ecological impact. However, not all green solvents are suitable for the wide scope of organic chemistry reactions. A second point to consider is that 50% of pharmaceutical drugs are nitrogen heterocycles compounds. It therefore appeared important to provide an overview of the more ecological methodologies for synthesizing this class of compounds. In this review, all publications since 2000 that describe green reactions leading to the formation of nitrogen heterocycles using safe solvents were considered. We chose water, PEG, and bio-based solvents for their negligible toxicity. The synthesis of five-, six-, and seven-membered aromatic nitrogen heterocycles using green reactions reported in the literature to date is described.
PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions
Authors: Wiatrak Benita , Kubis-Kubiak Adriana , Piwowar Agnieszka , Barg Ewa
Published: April 2020

The PC12 cell line is one of the most commonly used in neuroscience research, including studies on neurotoxicity, neuroprotection, neurosecretion, neuroinflammation, and synaptogenesis. Two types of this line are available in the ATCC collection: traditional PC12 cells grown in suspension and well-attached adherent phenotype. PC12 cells grown in suspension tend to aggregate and adhere poorly to non-coated surfaces. Therefore, it is necessary to modify the surface of culture vessels. This paper aims to characterise the use of two distinct variants of PC12 cells as well as describe their differentiation and neuronal outgrowth with diverse NGF concentrations (rat or human origin) on various surfaces. In our study, we evaluated cell morphology, neurite length, density and outgrowth (measured spectrofluorimetrically), and expression of neuronal biomarkers (doublecortin and NeuN). We found that the collagen coating was the most versatile method of surface modification for both cell lines. For adherent cells, the coating was definitely less important, and the poly-d-lysine surface was as good as collagen. We also demonstrated that the concentration of NGF is of great importance for the degree of differentiation of cells. For suspension cells, we achieved the best neuronal characteristics (length and density of neurites) after 14 days of incubation with 100 ng/mL NGF (change every 48 h), while for adherent cells after 3–5 days, after which they began to proliferate. In the PC12 cell line, doublecortin (DCX) expression in the cytoplasm and NeuN in the cell nucleus were found. In turn, in the PC12 Adh line, DCX was not expressed, and NeuN expression was located in the entire cell (both in the nucleus and cytoplasm). Only the traditional PC12 line grown in suspension after differentiation with NGF should be used for neurobiological studies, especially until the role of the NeuN protein, whose expression has also been noted in the cytoplasm of adherent cells, is well understood.
The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway
Authors: Leite Jefferson Antônio , Pessenda Gabriela , Guerra-Gomes Isabel C. , de Santana Alynne Karen Mendonça , André Pereira Camila , Ribeiro Campos Costa Frederico , Ramos Simone G. , Simões Zamboni Dario , Caetano Faria Ana Maria , Candido de Almeida Danilo , Olsen Saraiva Câmara Niels , Tostes Rita C. , Santana Silva João , Carlos Daniela
Published: April 2020

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.
The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death
Authors: Lavrin Teja , Konte Tilen , Kostanjšek Rok , Sitar Simona , Sepčič Kristina , Prpar Mihevc Sonja , Žagar Ema , Župunski Vera , Lenassi Metka , Rogelj Boris , Gunde Cimerman Nina
Published: April 2020

The neurotropic and extremophilic black yeast Exophiala dermatitidis (Herpotrichellaceae) inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the selected strain, EXF-10123, is polymorphic, can grow at 37 °C, is able to assimilate aromatic hydrocarbons (toluene, mineral oil, n-hexadecane), and shows abundant growth with selected neurotransmitters (acetylcholine, gamma-aminobutyric acid, glycine, glutamate, and dopamine) as sole carbon sources. We have for the first time demonstrated the effect of E. dermatitidis on neuroblastoma cell model SH-SY5Y. Aqueous and organic extracts of E. dermatitidis biomass reduced SH-SY5Y viability by 51% and 37%, respectively. Melanized extracellular vesicles (EVs) prepared from this strain reduced viability of the SH-SY5Y to 21%, while non-melanized EVs were considerably less neurotoxic (79% viability). We also demonstrated direct interactions of E. dermatitidis with SH-SY5Y by scanning electron and confocal fluorescence microscopy. The observed invasion and penetration of neuroblastoma cells by E. dermatitidis hyphae presumably causes the degradation of most neuroblastoma cells in only three days. This may represent a so far unknown indirect or direct cause for the development of some neurodegenerative diseases such as Alzheimer’s.
Aldosterone Decreases Vasopressin-Stimulated Water Reabsorption in Rat Inner Medullary Collecting Ducts
Authors: Wang Yanhua , Ma Fuying , Rodriguez Eva L. , Klein Janet D. , Sands Jeff M.
Published: April 2020

Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.
The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation
Authors: Thornton Shantae M. , Samararatne Varsha D. , Skeate Joseph G. , Buser Christopher , Lühen Kim P. , Taylor Julia R. , Da Silva Diane M. , Kast W. Martin
Published: April 2020

Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.
Oxidized Phospholipids in Healthy and Diseased Lung Endothelium
Authors: Karki Pratap , Birukov Konstantin G.
Published: April 2020

Circulating and cell membrane phospholipids undergo oxidation caused by enzymatic and non-enzymatic mechanisms. As a result, a diverse group of bioactive oxidized phospholipids generated in these conditions have both beneficial and harmful effects on the human body. Increased production of oxidized phospholipid products with deleterious effects is linked to the pathogenesis of various cardiopulmonary disorders such as atherosclerosis, thrombosis, acute lung injury (ALI), and inflammation. It has been determined that the contrasting biological effects of lipid oxidation products are governed by their structural variations. For example, full-length products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC) have prominent endothelial barrier protective and anti-inflammatory activities while most of the truncated oxidized phospholipids induce vascular leak and exacerbate inflammation. The extensive studies from our group and other groups have demonstrated a strong potential of OxPAPC in mitigating a wide range of agonist-induced lung injuries and inflammation in pulmonary endothelial cell culture and rodent models of ALI. Concurrently, elevated levels of truncated oxidized phospholipids are present in aged mice lungs that potentiate the inflammatory agents-induced lung injury. On the other hand, increased levels of full length OxPAPC products accelerate ALI recovery by facilitating production of anti-inflammatory lipid mediator, lipoxin A4, and other molecules with anti-inflammatory properties. These findings suggest that OxPAPC-assisted lipid program switch may be a promising therapeutic strategy for treatment of acute inflammatory syndromes. In this review, we will summarize the vascular-protective and deleterious aspects of oxidized phospholipids and discuss their therapeutic potential including engineering of stable analogs of oxidized phospholipids with improved anti-inflammatory and barrier-protective properties.
Necroptosis in Cholangiocarcinoma
Authors: Sarcognato Samantha , de Jong Iris E. M. , Fabris Luca , Cadamuro Massimiliano , Guido Maria
Published: April 2020

Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.
A Review of Recent Research on Contamination of Oil Well Cement with Oil-based Drilling Fluid and the Need of New and Accurate Correlations
Authors: Arbad Nachiket , Teodoriu Catalin
Published: April 2020

Drilling fluids and oil well cement are important well barriers. Their compatibility affects the long-term integrity of the well. The mixing of drilling fluid with the oil well cement causes contamination of oil well cement. If the contamination is due to diesel/oil-based drilling fluid (OBF) it adversely affects the rheological and mechanical properties of oil well cement—in other words, the long-term integrity of the well. An initial study on OBF contamination of oil well cement was carried out two decades ago. In recent years, several research projects were carried out on the same topic to understand the reason for changes in the properties of oil well cement with OBF contamination. This literature review shows that using OBF eliminates several drilling problems, as the long-term integrity of the well depends on the amount of OBF contamination in the cement slurry. This paper compares the experiments performed, results and conclusions drawn from selected research studies on OBF contamination of oil well cement. Their shortcomings and a way forward are discussed in detail. A critical review of these research studies highlights the need for new and accurate correlations for OBF-contaminated oil well cement to predict the long-term integrity of wells.
A Study of the Interaction between Cucurbit[7]uril and Alkyl Substituted 4-Pyrrolidinopyridinium Salts
Authors: Xu Weitao , Zhu Xinyi , Bian Bing , Xiao Xin , Tao Zhu , Redshaw Carl
Published: April 2020

The interaction between cucurbit[7]uril (Q[7]) and a series of 4-pyrrolidinopyridinium salts bearing aliphatic substituents at the pyridinium nitrogen, namely 4-(C4H8N)C5H5NRBr, where R = H (C0), Et (C2), n-butyl (C4), n-hexyl (C6), has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy, and mass spectrometry.