bluuebunny/crossref_metadata_2025 huggingface dataset:
A 28 Day Clinical Assessment of a Lactic Acid-containing Antimicrobial Intimate Gel Wash Formulation on Skin Tolerance and Impact on the Vulvar Microbiome
Authors: Bruning Elizabeth , Chen Ying , McCue Karen A. , Rubino Joseph R. , Wilkinson Jeremy E. , Brown Alan D. G.
Published: February 2020

While intimate feminine hygiene products are widely used as part of daily cleansing routines, little is known about how these products impact the vulvovaginal area and its microbiome stability. This 4 week clinical study assessed tolerance of a novel gel wash containing lactic acid (pH 4.2) for external daily use when used on the external genital area and its effects on skin moisturization, vulvar skin pH, and the vulvar microbiome. After a 7 day pre-study conditioning period, 36 healthy females in three balanced age groups (18–29, 30–44, and 45–55 years) used the gel wash to cleanse their external genital area (mons pubis and vulva) and entire body at least once per day for 28 days. Skin tolerance of the gel wash was assessed by the gynecologist. Effects of the gel wash on vulvar skin microbiota were studied by performing bacterial 16S rRNA and fungal internal transcribed spacer (ITS) microbial richness and diversity analysis. Based on gynecologic assessment after 28 days of use, the gel wash showed acceptable tolerance, with no signs of increased dryness, redness, edema, itching, stinging, or burning. Use of the gel wash was associated with a significant increase in both short-term (single application) and longer-term (daily use for 28 days) skin moisturization. There was no significant change in vulvar skin pH over time with daily product use, and the gel wash did not significantly affect the natural vulvar microbiome species richness or diversity for bacteria or fungi. Results showed that this gel wash is a mild, moisturizing cleanser that maintains the natural pH and microbial diversity of vulvar skin. To our knowledge, this was the first study to assess the effect of an antimicrobial feminine gel wash on the natural pH and vulvar microbiome habitat of the skin using bacterial 16S rRNA and fungal ITS genetic sequencing techniques.
Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails
Authors: Smith R. , Russo J. , Fiegel J. , Brogden N.
Published: February 2020

The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the “microbiota”) that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.
UHPLC-HESI-OT-MS-MS Biomolecules Profiling, Antioxidant and Antibacterial Activity of the “Orange-Yellow Resin” from Zuccagnia punctata Cav.
Authors: Gómez Jessica , Simirgiotis Mario J. , Manrique Sofía , Lima Beatriz , Bórquez Jorge , Feresin Gabriela E. , Tapia Alejandro
Published: February 2020

This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential antioxidant and antibacterial, properties of orange-yellow resin from Zuccagnia punctata Cav (ZpRe). Metabolite profiling was obtained by a ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (LP)). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The resin displayed a strong DPPH scavenging activity (IC50 = 25.72 µg/mL) and showed a percentage of inhibition of LP close to that of the reference compound catechin (70% at 100 µg ZpRe/mL), while a moderated effect was observed in the FRAP and TEAC assays. The resin showed a content of phenolic and flavonoid compounds of 391 mg GAE/g and 313 mg EQ/g respectively. Fifty phenolics compounds were identified by ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-PDA-OT-MS) analysis. Thirty-one compounds are reported for the first time, updating the knowledge on the chemical profile of this species. The importance of the biomolecules identified support traditional use of this endemic plant. Furthermore, additional pharmacological data is presented that increase the potential interest of this plant for industrial sustainable applications.
A Novel Pectic Polysaccharide of Jujube Pomace: Structural Analysis and Intracellular Antioxidant Activities
Authors: Lin Ximeng , Liu Keshan , Yin Sheng , Qin Yimin , Shen Peili , Peng Qiang
Published: February 2020

After extraction from jujube pomace and purification by two columns (DEAE-Sepharose Fast Flow and Sepharcyl S-300), the structure of SAZMP4 was investigated by HPGPC, GC, FI-IR, GC-MS, NMR, SEM, and AFM. Analysis determined that SAZMP4 (Mw = 28.94 kDa) was a pectic polysaccharide mainly containing 1,4-linked GalA (93.48%) with side chains of 1,2,4-linked Rha and 1,3,5-linked Ara and terminals of 1-linked Rha and 1-linked Ara, which might be the homogalacturonan (HG) type with side chains of the RG-I type, corresponding to the results of NMR. In AFM and SEM images, self-assembly and aggregation of SAZMP4 were respectively observed indicating its structural features. The antioxidant activity of SAZMP4 against H2O2-induced oxidative stress in Caco-2 cells was determined by activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as malondialdehyde (MDA) and reactive oxygen species (ROS) levels, indicating SAZMP4 can be a natural antioxidant. Also, a better water retention capacity and thermal stability of SAZMP4 was observed based on DSC analysis, which could be applied in food industry as an additive.
Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance
Authors: Cruz Adriana , Mota Pedro , Ramos Cristiano , Pires Rita F. , Mendes Cindy , Silva José P. , Nunes Sofia C. , Bonifácio Vasco D. B. , Serpa Jacinta
Published: February 2020

Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to l-buthionine sulfoximine (l-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (l-BSO@PUREG4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle.
Considering Uncertainties of Key Performance Indicators in Wind Turbine Operation
Authors: Pfaffel Sebastian , Faulstich Stefan , Rohrig Kurt
Published: February 2020

Key performance indicators (KPIs) are commonly used in the wind industry to support decision-making and to prioritize the work throughout a wind turbine portfolio. Still, there is little knowledge of the uncertainties of KPIs. This article intends to shed some light on the uncertainty and reliability of KPIs in general and performance KPIs in particular. For this purpose, different uncertainty causes are discussed, and three data handling related uncertainty causes are analyzed in detail for five KPIs. A local sensitivity analysis is followed by a more detailed analysis of the related uncertainties. The work bases on different sets of operational data, which are manipulated in a large number of experiments to carry out an empirical uncertainty analysis. The results show that changes in the data resolution, data availability, as well as missing inputs, can cause considerable uncertainties. These uncertainties can be reduced or even mitigated by simple measures in many cases. This article provides a comprehensive list of statements and recommendations to estimate the relevance of data handling related KPI uncertainties in the day-to-day work as well as approaches to correct KPIs for systematic deviations and simple steps to avoid pitfalls.
Topology Optimization for Multipatch Fused Deposition Modeling 3D Printing
Authors: Yu Huangchao , Hong Huajie , Cao Su , Ahmad Rafiq
Published: February 2020

This paper presents a hybrid topology optimization method for multipatch fused deposition modeling (FDM) 3D printing to address the process-induced material anisotropy. The ‘multipatch’ concept consists of each printing layer disintegrated into multiple patches with different zigzag-type filament deposition directions. The level set method was employed to represent and track the layer shape evolution; discrete material optimization (DMO) model was adopted to realize the material property interpolation among the patches. With this set-up, a concurrent optimization problem was formulated to simultaneously optimize the topological structure of the printing layer, the multipatch distribution, and the corresponding deposition directions. An asynchronous starting strategy is proposed to prevent the local minimum solutions caused by the concurrent optimization scheme. Several numerical examples were investigated to verify the effectiveness of the proposed method, while satisfactory optimization results have been derived.
Predictive Data Mining Techniques for Fault Diagnosis of Electric Equipment: A Review
Authors: Contreras-Valdes Arantxa , Amezquita-Sanchez Juan P. , Granados-Lieberman David , Valtierra-Rodriguez Martin
Published: February 2020

Data mining is a technological and scientific field that, over the years, has been gaining more importance in many areas, attracting scientists, developers, and researchers around the world. The reason for this enthusiasm derives from the remarkable benefits of its usefulness, such as the exploitation of large databases and the use of the information extracted from them in an intelligent way through the analysis and discovery of knowledge. This document provides a review of the predictive data mining techniques used for the diagnosis and detection of faults in electric equipment, which constitutes the pillar of any industrialized country. Starting from the year 2000 to the present, a revision of the methods used in the tasks of classification and regression for the diagnosis of electric equipment is carried out. Current research on data mining techniques is also listed and discussed according to the results obtained by different authors.
Search for the Developing Trends by Patent Analysis: A Case Study of Lithium-Ion Battery Electrolytes
Authors: Lee Ming-Ta , Su Wei-Nien
Published: February 2020

Lithium-ion batteries (LIBs) are now used in electric vehicles (EVs), and the electrolyte is one of the major components governing the performance of LIBs. The patent count-based method or patent indicator was used to understand the development status of the specific technology field. However, these approaches cannot provide a complete picture to realize the technology development. Therefore, the goal of this work is to develop a holistic approach to identify technological development trends. The top six patent assignees are first selected by an issued patent counts analysis, including Ube, Mitsubishi Chem., Panasonic, Sony, LG Chem., and Samsung SDI. The “modified” Ernst indicators are applied to reflect different innovation strategies among these patent assignees. The forward-citation analysis and technology-function matrix show that using mixed lithium salts and organic solvents with novel additives compounds are the developing trends to improve the performance of LIBs. The multi-dimensional scaling shows technological similarities among these six companies. The developed approaches can be used to obtain a better overview for electrolyte technology and be also applicable to other technological fields.
A Wi-Fi FTM-Based Indoor Positioning Method with LOS/NLOS Identification
Authors: Si Minghao , Wang Yunjia , Xu Shenglei , Sun Meng , Cao Hongji
Published: February 2020

In recent years, many new technologies have been used in indoor positioning. In 2016, IEEE 802.11-2016 created a Wi-Fi fine timing measurement (FTM) protocol, making Wi-Fi ranging more robust and accurate, and providing meter-level positioning accuracy. However, the accuracy of positioning methods based on the new ranging technology is influenced by non-line-of-sight (NLOS) errors. To enhance the accuracy, a positioning method with LOS (line-of-sight)/NLOS identification is proposed in this paper. A Gaussian model has been established to identify NLOS signals. After identifying and discarding NLOS signals, the least square (LS) algorithm is used to calculate the location. The results of the numerical experiments indicate that our algorithm can identify and discard NLOS signals with a precision of 83.01% and a recall of 74.97%. Moreover, compared with the traditional algorithms, by all ranging results, the proposed method features more accurate and stable results for indoor positioning.
Ensuring Computers Understand Manual Operations in Production: Deep-Learning-Based Action Recognition in Industrial Workflows
Authors: Jiao Zeyu , Jia Guozhu , Cai Yingjie
Published: February 2020

In this study, we consider fully automated action recognition based on deep learning in the industrial environment. In contrast to most existing methods, which rely on professional knowledge to construct complex hand-crafted features, or only use basic deep-learning methods, such as convolutional neural networks (CNNs), to extract information from images in the production process, we exploit a novel and effective method, which integrates multiple deep-learning networks including CNNs, spatial transformer networks (STNs), and graph convolutional networks (GCNs) to process video data in industrial workflows. The proposed method extracts both spatial and temporal information from video data. The spatial information is extracted by estimating the human pose of each frame, and the skeleton image of the human body in each frame is obtained. Furthermore, multi-frame skeleton images are processed by GCN to obtain temporal information, meaning the action recognition results are predicted automatically. By training on a large human action dataset, Kinetics, we apply the proposed method to the real-world industrial environment and achieve superior performance compared with the existing methods.
A Fast Hole-Filling Method for Triangular Mesh in Additive Repair
Authors: Feng Chao , Liang Jin , Ren Maodong , Qiao Gen , Lu Wang , Liu Shifan
Published: February 2020

In the triangular meshes obtained in additive repair, it is a challenge to find one single hole-filling method to close all holes and make the filling patches assort with surrounding meshes well with low time complexity, which is mainly caused by the shape complexity and size difference of the various holes, especially in the fields of intelligent manufacturing, 3D measurement, and reverse engineering. Therefore, it is reasonable to adopt different algorithms to fill different types of holes. In this research, a fast hole-filling method for triangular mesh is proposed based on the hole size. First, a group of basic concepts is defined to make them uniform throughout the whole text, followed by the descriptions of hole detection and boundary cleaning. Second, three different algorithms are developed to fill the small-sized, middle-sized, and large-sized holes classified by hole size respectively, which can fill all the detected holes in a fast and proper manner. Finally, two experiments are carried out to verify the efficiency, robustness, and ability to recover the shape of our method. Compared to two state-of-the-art hole-filling methods in the first experiment, the quantitative evaluation results demonstrate that our proposed method is much faster than them with the ability to guarantee the regularity of most filling triangles. The second experiment proves that our method can produce satisfactory filling results by making the filling patches be compatible with surrounding meshes well.
Recent Research Progress in Surface Ligand Exchange of PbS Quantum Dots for Solar Cell Application
Authors: You Hyung Ryul , Park Jin Young , Lee Duck Hoon , Kim Younghoon , Choi Jongmin
Published: February 2020

Colloidal quantum dots (CQDs) are considered as next-generation semiconductors owing to their tunable optical and electrical properties depending on their particle size and shape. The characteristics of CQDs are mainly governed by their surface chemistry, and the ligand exchange process plays a crucial role in determining their surface states. Worldwide studies toward the realization of high-quality quantum dots have led to advances in ligand exchange methods, and these procedures are usually carried out in either solid-state or solution-phase. In this article, we review recent advances in solid-state and solution-phase ligand exchange processes that enhance the performance and stability of lead sulfide (PbS) CQD solar cells, including infrared (IR) CQD photovoltaics.
An Exploratory Analysis of the Implementation and Use of an Intelligent Platform for Learning in Primary Education
Authors: Lara Nieto-Márquez Natalia , Baldominos Alejandro , Cardeña Martínez Alejandro , Pérez Nieto Miguel Ángel
Published: February 2020

Smile and Learn is an intelligent platform with more than 4500 educational activities for children aged 3–12. The digital material developed covers all courses of primary education and most of the subjects with the different topic-related worlds with activities in the field of logics and mathematics, science, linguistics and tales, visual-spatial and cognitive skills, emotional intelligence, arts, and multiplayer games. This kind of material supports active learning and new pedagogical models for teachers to use in their lessons. The purpose of this paper is to explore the usage of the platform in three pilot groups schools from different regions of Spain, outlining future directions in the design of such digital materials. Usage is assessed via descriptive analysis and variance analysis, with data collected from users interacting with the intelligent platform. The results show a high use of STEM (Science, Technology, Engineering and Maths) activities among all the activities that could be chosen. Cross-curricular activities are also used. Continuation in the development of such materials is concluded necessary, focusing integration of different fields, accentuating games over quizzes, and the value of teacher training for improving their use in schools.
Strain and Growth Conditions may Regulate Resistance of Listeria monocytogenes Biofilms to Benzalkonium Chloride
Authors: Bonneville Lourenço , Ortiz Sagrario , Maia Vera , Brito Luisa , Martínez-Suárez Joaquín V.
Published: February 2020

Listeria monocytogenes is one of the main foodborne pathogens. The formation of biofilms by L. monocytogenes contributes to its resistance to disinfectants, which represents a serious risk for food production plants. The aim of this study was to compare the effect of sub-inhibitory concentrations of benzalkonium chloride (BAC) (1.25 or 2.5 mg/L) on biofilm production and on biofilm reduction after exposure to an inhibitory concentration of BAC (1280 mg/L) in two isogenic L. monocytogenes strains: the BAC-sensitive wild-type strain S2-1 and its BAC-resistant mutant derivative S2BAC, which presented a multidrug resistance phenotype. The biofilm-forming ability of the strains under different BAC concentrations was evaluated by the resazurin method using polystyrene microplates. The biofilm reduction after BAC exposure was evaluated by using stainless steel coupons (SSCs). When the resazurin method was used, S2BAC produced significantly more biofilm in the presence of a sub-inhibitory concentration of BAC compared to that in the culture medium without BAC (p < 0.05). When the SSC method was used, the presence of sub-inhibitory concentrations of BAC resulted in a higher resistance of the biofilm for S2BAC compared to that in the culture medium without BAC (p < 0.05). This was not observed with the sensitive S2-1 strain. These results suggest that biofilm behavior depends on the strain and sub-inhibitory concentrations of disinfectants and may explain the ability of certain isolates to persist in niches of food processing plants.
Effects on Biodiesel Production Caused by Feed Oil Changes in a Continuous Stirred-Tank Reactor
Authors: Castillo Gónzalez Juan P. , Álvarez Gutiérrez Peggy E. , Adam Medina Manuel , López Zapata Betty Y. , Ramírez Guerrero Gerardo V. , Vela Valdés Luis G.
Published: February 2020

Continuous production processes and an adequate supply of raw materials are necessary to satisfy the growing demand for biodiesel. The use of different feed oils could be necessary to ensure sufficient supply for biodiesel production in certain circumstances; however, changing feed oil during the operation of a continuous reactor causes process disturbances. The present study analyses the effect of feed oil changes on the continuous operation of a industrial continuous stirred-tank reactor (CSTR) using a model which takes the dynamics of oil changes into account. The models previously reported only consider the operation of reactor with only one vegetable oil. The model in this work was developed by mass and energy balances. A methodology to model oil changes is presented. Glycerides and esters were characterized using adequate approaches. Moreover, accurate methods for predicting essential properties in the biodiesel manufacturing were used for the estimation of their thermo-physical properties. The kinetic parameters of the transesterifications were calculated from consistent studies selected from an exhaustive literature revision. The results show that temperature is practically not affected after oil changes; however, the ester concentration varies considerably. The ester mass fraction varying by up to 22.07% after an disturbance.
Effect of Calcination Temperature on Photocatalytic Activity of Synthesized TiO2 Nanoparticles via Wet Ball Milling Sol-Gel Method
Authors: Phromma Siripond , Wutikhun Tuksadon , Kasamechonchung Panita , Eksangsri Tippabust , Sapcharoenkun Chaweewan
Published: February 2020

In this work, TiO2 nanoparticles were successfully synthesized with narrow size distribution via a wet ball milling sol-gel method. The effect of calcination temperature on photocatalytic activity was observed from particle size, crystallite size, and phase transition of TiO2 nanoparticles. Increasing calcination temperature increased particle size, crystallite size, and the crystallinity of synthesized TiO2. Phase transition depended on variation in calcination temperatures. A two-phase mixture of anatase and brookite was obtained with lower calcination temperature whereas a three-phase mixture appeared when calcination temperature was 500–600 °C. With higher temperature, the rutile phase kept increasing until it was the only phase observed at 800 °C. Anatase strongly affected the photocatalytic activity from 300 °C to 600 °C while the particle size of TiO2 was found to have a dominant effect on the photocatalytic activity between 600 °C and 700 °C. A mixture of three phases of TiO2-600 exhibited the highest methylene blue degradation with the rate constant of 9.46 × 10−2 h−1 under ultraviolet (UV) irradiation.
An Observational Study of the Symmetric Boundary Layer Structure and Tropical Cyclone Intensity
Authors: Ren Yifang , Zhang Jun A. , Vigh Jonathan L. , Zhu Ping , Liu Hailong , Wang Xiang , Wadler Joshua B.
Published: February 2020

This study analyses Global Positioning System dropsondes to document the axisymmetric tropical cyclone (TC) boundary-layer structure, based on storm intensity. A total of 2608 dropsondes from 42 named TCs in the Atlantic basin from 1998 to 2017 are used in the composite analyses. The results show that the axisymmetric inflow layer depth, the height of maximum tangential wind speed, and the thermodynamic mixed layer depth are all shallower in more intense TCs. The results also show that more intense TCs tend to have a deep layer of the near-saturated air inside the radius of maximum wind speed (RMW). The magnitude of the radial gradient of equivalent potential temperature (θe) near the RMW correlates positively with storm intensity. Above the inflow layer, composite structures of TCs with different intensities all possess a ring of anomalously cool temperatures surrounding the warm-core, with the magnitude of the warm-core anomaly proportional to TC intensity. The boundary layer composites presented here provide a climatology of how axisymmetric TC boundary layer structure changes with intensity.
Syzygium aromaticum L. (Myrtaceae): Traditional Uses, Bioactive Chemical Constituents, Pharmacological and Toxicological Activities
Authors: El-Saber Batiha Gaber , Alkazmi Luay M. , Wasef Lamiaa G. , Beshbishy Amany Magdy , Nadwa Eman H. , Rashwan Eman K.
Published: February 2020

Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, and β-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Several reports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistant Staphylococcus epidermidis and S. aureus. Moreover, eugenol was found to protect against CCl4−induced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including Giardia lamblia, Fasciola gigantica, Haemonchus contortus, and Schistosoma mansoni. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis.
Microwave-Assisted versus Conventional Isolation of Glucosinolate Degradation Products from Lunaria annua L. and Their Cytotoxic Activity
Authors: Blažević Ivica , Đulović Azra , Čikeš Čulić Vedrana , Popović Marijana , Guillot Xavier , Burčul Franko , Rollin Patrick
Published: February 2020

Glucosinolates (GSLs) from Lunaria annua L. seeds were analyzed qualitatively and quantitatively by their desulfo counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown products, isothiocyanates (ITCs), using GC-MS technique. GSL breakdown products were obtained by conventional techniques (hydrodistillation in a Clevenger type apparatus (HD), CH2Cl2 extraction after myrosinase hydrolysis (EXT) for 24 h) as well as by modern techniques, microwave-assisted distillation (MAD) and microwave hydrodiffusion and gravity (MHG). Seven GSLs were identified as follows: isopropyl GSL (1), sec-butyl GSL (2), 5-(methylsulfinyl)pentyl GSL (3), 6-(methylsulfinyl)hexyl GSL (4), 5-(methylsulfanyl)pentyl GSL (5), 6-(methylsulfanyl)hexyl GSL (6), and benzyl GSL (7). Additionally, pent-4-enyl- and hex-5-enyl ITCs were detected in the volatile extracts. However, their corresponding GSLs were not detected using UHPLC-DAD-MS/MS. Thus, they are suggested to be formed during GC-MS analysis via thermolysis of 5-(methylsulfinyl)pentyl- and 6-(methylsulfinyl)hexyl ITCs, respectively. Volatile isolates were tested for their cytotoxic activity using MTT assay. EXT and MHG showed the best cytotoxic activity against human lung cancer cell line A549 during an incubation time of 72 h (IC50 18.8, and 33.5 μg/mL, respectively), and against breast cancer cell line MDA-MB-231 after 48 h (IC50 6.0 and 11.8 μg/mL, respectively). These activities can be attributed to the ITCs originating from 3 and 4.
The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions
Authors: Rizzo Gianluca , Laganà Antonio Simone
Published: February 2020

Omega-3 polyunsaturated fatty acids and B vitamins are linked to metabolic and degenerative disorders, such as cardiovascular disease and cognitive decline. In the last two decades, the interplay between B vitamins and omega-3 polyunsaturated fatty acids gained increasing attention. Expression control on enzymes involved in the pathway of homocysteine by polyunsaturated fatty acids has been proposed. The methylation process seems crucial for the metabolism of polyunsaturated fatty acids and their distribution within the body. This review summarizes the available data in humans about the link between homocysteine and omega-3 polyunsaturated fatty acids, with a special focus on the meta-analyses of randomized clinical trials. Even if the paucity of available information about the topic does not allow for definitive conclusions, a synergic action between polyunsaturated fatty acids and B vitamins may play a key role in regulating several metabolic pathways. This element could explain a stronger action on homocysteine levels when omega-3 polyunsaturated fatty acids and B vitamins are supplemented simultaneously. To date, a robust rationale of intervention to prevent metabolic diseases is lacking and could be beneficial for individual health and healthcare policy.
Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice
Authors: Méndez-González Miguel P. , Rivera-Aponte David E. , Benedikt Jan , Maldonado-Martínez Geronimo , Tejeda-Bayron Flavia , Skatchkov Serguei N. , Eaton Misty J.
Published: February 2020

Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% of diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording in hippocampal brain slices from male mice, we determined the electrophysiological properties of stratum radiatum astrocytes and CA1 pyramidal neurons. In diabetic mice, astrocytic Kir4.1 channels were functionally downregulated as evidenced by multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents and impaired potassium uptake capabilities of hippocampal astrocytes. Furthermore, CA1 pyramidal neurons from diabetic mice displayed increased spontaneous activity: action potential frequency was ≈9 times higher in diabetic compared with non-diabetic mice and small EPSC event frequency was significantly higher in CA1 pyramidal cells of diabetics compared to non-diabetics. These differences were apparent in control conditions and largely pronounced in response to the pro-convulsant 4-aminopyridine. Our data suggest that astrocytic dysfunction due to downregulation of Kir4.1 channels may increase seizure susceptibility by impairing astrocytic ability to maintain proper extracellular homeostasis.
Ixazomib Improves Bone Remodeling and Counteracts Sonic Hedgehog Signaling Inhibition Mediated by Myeloma Cells
Authors: Tibullo Daniele , Longo Anna , Vicario Nunzio , Romano Alessandra , Barbato Alessandro , Di Rosa Michelino , Barbagallo Ignazio , Anfuso Carmelina Daniela , Lupo Gabriella , Gulino Rosario , Parenti Rosalba , Li Volti Giovanni , Palumbo Giuseppe Alberto , Di Raimondo Francesco , Giallongo Cesarina
Published: February 2020

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of plasma cells (PC) in the bone marrow (BM), leading to bone loss and BM failure. Osteolytic bone disease is a common manifestation observed in MM patients and represents the most severe cause of morbidity, leading to progressive skeletal damage and disabilities. Pathogenetic mechanisms of MM bone disease are closely linked to PCs and osteoclast (OCs) hyperactivity, coupled with defective osteoblasts (OBs) function that is unable to counteract bone resorption. The aim of the present study was to investigate the effects of Ixazomib, a third-generation proteasome inhibitor, on osteoclastogenesis and osteogenic differentiation. We found that Ixazomib was able to reduce differentiation of human monocytes into OCs and to inhibit the expression of OC markers when added to the OC medium. Concurrently, Ixazomib was able to stimulate osteogenic differentiation of human mesenchymal stromal cells (MSCs), increasing osteogenic markers, either alone or in combination with the osteogenic medium. Given the key role of Sonic Hedgehog (SHH) signaling in bone homeostasis, we further investigated Ixazomib-induced SHH pathway activation. This set of experiments showed that Ixazomib, but not Bortezomib, was able to bind the Smoothened (SMO) receptor leading to nuclear translocation of GLI1 in human MSCs. Moreover, we demonstrated that PCs act as GLI1 suppressors on MSCs, thus reducing the potential of MSCs to differentiate in OBs. In conclusion, our data demonstrated that Ixazomib regulates bone remodeling by decreasing osteoclastogenesis and prompting osteoblast differentiation via the canonical SHH signaling pathway activation, thus, representing a promising therapeutic option to improve the complex pathological condition of MM patients.
Ipilimumab and Its Derived EGFR Aptamer-Based Conjugate Induce Efficient NK Cell Activation against Cancer Cells
Authors: Passariello Margherita , Camorani Simona , Vetrei Cinzia , Ricci Stefania , Cerchia Laura , De Lorenzo Claudia
Published: February 2020

The immune checkpoint CTLA-4 (cytotoxic T-lymphocyte-antigen 4), which inhibits the co-stimulatory CD28 signal on T cells, has been recently found expressed on other cell populations, such as tumor and natural killer (NK) cells. We tested for the first time the effects of ipilimumab, the human anti-CTLA4 mAb in clinical use, on these cells and found that it inhibits the growth of tumor cells expressing CTLA-4 also in the absence of lymphocytes, and efficiently activates NK cells, thus suggesting an important unexplored role of NK cells in ipilimumab-modulated immune responses. Interestingly, the epidermal growth factor receptor (EGFR) has been shown to play a key role in tumor cell escape from immune surveillance, and in cytotoxic T lymphocyte inhibition. Thus, we tested combinatorial treatments of ipilimumab with an anti-EGFR aptamer endowed with anti-tumor activity, and constructed for the first time a novel bispecific immunoconjugate, made up of these two compounds. The novel immunoconjugate binds to the target cells, induces the activation of lymphocytes, including NK cells, and inhibits the growth of tumor target cells more efficiently than the parental compounds, by strongly enhancing the cytotoxic activity of both human peripheral blood mononuclear cells and NK cells against tumor cells.
C20orf27 Promotes Cell Growth and Proliferation of Colorectal Cancer via the TGFβR-TAK1-NFĸB Pathway
Authors: Gao Jing , Wang Yang , Zhang Weixia , Zhang Jing , Lu Shaohua , Meng Kun , Yin Xingfeng , Sun Zhenghua , He Qing-Yu
Published: February 2020

Background: Colorectal cancer (CRC) is a high incidence of malignant tumors that lacks highly effective and targeted drugs and thus it is in urgent need of finding new specific molecular targets. Methods and Results: In this study, by using WST-1 (Highly water-soluble tetrazolium salt-1) and colony formation assays, we found that C20orf27 (chromosome 20 open reading frame 27), a functionally unknown protein, enhanced the growth and proliferation of CRC cells. The nude mouse tumor formation experiments verified that C20orf27 promoted the growth of CRC. Signal pathway analysis identified the TGFβR-TAK1-NFĸB cascade as a mediator in C20orf27-induced CRC progression. Inhibition experiments using NFĸB inhibitors reversed this progression. Co-immunoprecipitation showed that C20orf27 promoted the activation of the TGFβR-TAK1-NFĸB pathway by interacting with PP1c (the catalytic subunit of type 1 phosphatase). Conclusions: Our results firstly characterized the functional role and molecular mechanism of C20orf27 in driving CRC growth and proliferation through the TGFβR-TAK1-NFĸB pathway, suggesting its potential as a novel CRC candidate therapeutic target and tumor marker.
Effect of Water Molecule on Photo-Assisted Nitrous Oxide Decomposition over Oxotitanium Porphyrin: A Theoretical Study
Authors: Maitarad Phornphimon , Promarak Vinich , Shi Liyi , Namuangruk Supawadee
Published: February 2020

Water vapor has generally been recognized as an inhibitor of catalysts in nitrous oxide (N2O) decomposition because it limits the lifetime of catalytic reactors. Oxygen produced in reactions also deactivates the catalytic performance of bulk surface catalysts. Herein, we propose a potential catalyst that is tolerant of water and oxygen in the process of N2O decomposition. By applying density functional theory calculations, we investigated the reaction mechanism of N2O decomposition into N2 and O2 catalyzed by oxotitanium(IV) porphyrin (TiO-por) with interfacially bonded water. The activation energies of reaction Path A and B are compared under thermal and photo-assisted conditions. The obtained calculation results show that the photo-assisted reaction in Path B is highly exothermic and proceeds smoothly with the low activation barrier of 27.57 kcal/mol at the rate determining step. The produced O2 is easily desorbed from the surface of the catalyst, requiring only 4.96 kcal/mol, indicating the suppression of catalyst deactivation. Therefore, TiO-por is theoretically proved to have the potential to be a desirable catalyst for N2O decomposition with photo-irradiation because of its low activation barrier, water resistance, and ease of regeneration.
Direct Hydroxylation of Phenol to Dihydroxybenzenes by H2O2 and Fe-based Metal-Organic Framework Catalyst at Room Temperature
Authors: Salazar-Aguilar Alma D. , Vega Gonzalo , Casas Jose A. , Vega-Díaz Sofía Magdalena , Tristan Ferdinando , Meneses-Rodríguez David , Belmonte Manuel , Quintanilla Asunción
Published: February 2020

A semi-crystalline iron-based metal-organic framework (MOF), in particular Fe-BTC, that contained 20 wt.% Fe, was sustainably synthesized at room temperature and extensively characterized. Fe-BTC nanopowders could be used as an efficient heterogeneous catalyst for the synthesis of dihydroxybenzenes (DHBZ), from phenol with hydrogen peroxide (H2O2), as oxidant under organic solvent-free conditions. The influence of the reaction temperature, H2O2 concentration and catalyst dose were studied in the hydroxylation performance of phenol and MOF stability. Fe-BTC was active and stable (with negligible Fe leaching) at room conditions. By using intermittent dosing of H2O2, the catalytic performance resulted in a high DHBZ selectivity (65%) and yield (35%), higher than those obtained for other Fe-based MOFs that typically require reaction temperatures above 70 °C. The long-term experiments in a fixed-bed flow reactor demonstrated good Fe-BTC durability at the above conditions.
Homogeneous and Heterogeneous Catalysis Impact on Pyrolyzed Cellulose to Produce Bio-Oil
Authors: Li Siyi , Cheng Shuo , Cross Jeffrey S.
Published: February 2020

Effectively utilizing catalytic pyrolysis to upgrade bio-oil products prepared from biomass has many potential benefits for the environment. In this paper, cellulose (a major component of plants and a biomass model compound) is pyrolyzed and catalyzed with different catalysts: Ni2Fe3, ZSM-5, and Ni2Fe3/ZSM-5. Two different pyrolysis processes are investigated to compare homogeneous and heterogeneous catalysis influence on the products. The results indicate that the Ni2Fe3 cluster catalyst shows the best activity as a homogeneous catalysis. It can also be recycled repeatedly, increases the yield of bio-oil, and improves the quality of the bio-oil by decreasing the sugar concentration. Furthermore, it also catalyzes the formation of a small amount of hydrocarbon compounds. In the case of Ni2Fe3/ZSM-5 catalyst, it shows a lower yield of bio-oil but also decreases the sugar concentration significantly. Ni2Fe3, not only can it be used as homogeneous catalysis mixed with cellulose but also shows catalytic activity as a supported catalyst on ZSM-5, with higher catalytic activity than ZSM-5. These results indicate that the Ni2Fe3 catalyst has significant activity for potential use in industry to produce high quality bio-oil from biomass.
RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism
Authors: Rolot Marion , O’Sullivan Timothy
Published: February 2020

Innate lymphoid cells (ILCs) are tissue-resident sentinels of the immune system that function to protect local tissue microenvironments against pathogens and maintain homeostasis. However, because ILCs are sensitively tuned to perturbations within tissues, they can also contribute to host pathology when critical activating signals become dysregulated. Recent work has demonstrated that the crosstalk between ILCs and their environment has a significant impact on host metabolism in health and disease. In this review, we summarize studies that support evidence for the ability of ILCs to influence tissue and systemic metabolism, as well as how ILCs can be regulated by environmental changes in systemic host metabolism. We also highlight studies demonstrating how ILC- intrinsic metabolism influences their activation, proliferation, and homeostasis. Finally, this review discusses the challenges and open questions in the rapidly expanding field of ILCs and immunometabolism.
Prolonged Hyperoxygenation Treatment Improves Vein Graft Patency and Decreases Macrophage Content in Atherosclerotic Lesions in ApoE3*Leiden Mice
Authors: Parma Laura , Peters Hendrika A. B. , Baganha Fabiana , Sluimer Judith C. , de Vries Margreet R. , Quax Paul H.A.
Published: February 2020

Unstable atherosclerotic plaques frequently show plaque angiogenesis which increases the chance of rupture and thrombus formation leading to infarctions. Hypoxia plays a role in angiogenesis and inflammation, two processes involved in the pathogenesis of atherosclerosis. We aim to study the effect of resolution of hypoxia using carbogen gas (95% O2, 5% CO2) on the remodeling of vein graft accelerated atherosclerotic lesions in ApoE3*Leiden mice which harbor plaque angiogenesis. Single treatment resulted in a drastic decrease of intraplaque hypoxia, without affecting plaque composition. Daily treatment for three weeks resulted in 34.5% increase in vein graft patency and increased lumen size. However, after three weeks intraplaque hypoxia was comparable to the controls, as were the number of neovessels and the degree of intraplaque hemorrhage. To our surprise we found that three weeks of treatment triggered ROS accumulation and subsequent Hif1a induction, paralleled with a reduction in the macrophage content, pointing to an increase in lesion stability. Similar to what we observed in vivo, in vitro induction of ROS in bone marrow derived macrophages lead to increased Hif1a expression and extensive DNA damage and apoptosis. Our study demonstrates that carbogen treatment did improve vein graft patency and plaque stability and reduced intraplaque macrophage accumulation via ROS mediated DNA damage and apoptosis but failed to have long term effects on hypoxia and intraplaque angiogenesis.
Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks
Authors: Riboni Laura , Abdel Hadi Loubna , Navone Stefania Elena , Guarnaccia Laura , Campanella Rolando , Marfia Giovanni
Published: February 2020

As a key hub of malignant properties, the cancer microenvironment plays a crucial role intimately connected to tumor properties. Accumulating evidence supports that the lysophospholipid sphingosine-1-phosphate acts as a key signal in the cancer extracellular milieu. In this review, we have a particular focus on glioblastoma, representative of a highly aggressive and deleterious neoplasm in humans. First, we highlight recent advances and emerging concepts for how tumor cells and different recruited normal cells contribute to the sphingosine-1-phosphate enrichment in the cancer microenvironment. Then, we describe and discuss how sphingosine-1-phosphate signaling contributes to favor cancer hallmarks including enhancement of proliferation, stemness, invasion, death resistance, angiogenesis, immune evasion and, possibly, aberrant metabolism. We also discuss the potential of how sphingosine-1-phosphate control mechanisms are coordinated across distinct cancer microenvironments. Further progress in understanding the role of S1P signaling in cancer will depend crucially on increasing knowledge of its participation in the tumor microenvironment.
An Automated, Single Cell Quantitative Imaging Microscopy Approach to Assess Micronucleus Formation, Genotoxicity and Chromosome Instability
Authors: Lepage Chloe C. , Thompson Laura L. , Larson Bradley , McManus Kirk J.
Published: February 2020

Micronuclei are small, extranuclear bodies that are distinct from the primary cell nucleus. Micronucleus formation is an aberrant event that suggests a history of genotoxic stress or chromosome mis-segregation events. Accordingly, assays evaluating micronucleus formation serve as useful tools within the fields of toxicology and oncology. Here, we describe a novel micronucleus formation assay that utilizes a high-throughput imaging platform and automated image analysis software for accurate detection and rapid quantification of micronuclei at the single cell level. We show that our image analysis parameters are capable of identifying dose-dependent increases in micronucleus formation within three distinct cell lines following treatment with two established genotoxic agents, etoposide or bleomycin. We further show that this assay detects micronuclei induced through silencing of the established chromosome instability gene, SMC1A. Thus, the micronucleus formation assay described here is a versatile and efficient alternative to more laborious cytological approaches, and greatly increases throughput, which will be particularly beneficial for large-scale chemical or genetic screens.