bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Omics Revealed Molecular Mechanisms Underlying Guard Cell Systemic Acquired Resistance
Authors: David Lisa , Kang Jianing , Dufresne Daniel , Zhu Dan , Chen Sixue
Published: December 2020

Systemic Acquired Resistance (SAR) improves immunity of plant systemic tissue after local exposure to a pathogen. Guard cells that form stomatal pores on leaf surfaces recognize bacterial pathogens via pattern recognition receptors, such as Flagellin Sensitive 2 (FLS2). However, how SAR affects stomatal immunity is not known. In this study, we aim to reveal molecular mechanisms underlying the guard cell response to SAR using multi-omics of proteins, metabolites and lipids. Arabidopsis plants previously exposed to pathogenic bacteria Pseudomonas syringae pv. tomato DC3000 (Pst) exhibit an altered stomatal response compared to control plants when they are later exposed to the bacteria. Reduced stomatal apertures of SAR primed plants lead to decreased number of bacteria in leaves. Multi-omics has revealed molecular components of SAR response specific to guard cells functions, including potential roles of reactive oxygen species (ROS) and fatty acid signaling. Our results show an increase in palmitic acid and its derivative in the primed guard cells. Palmitic acid may play a role as an activator of FLS2, which initiates stomatal immune response. Improved understanding of how SAR signals affect stomatal immunity can aid biotechnology and marker-based breeding of crops for enhanced disease resistance.
Distinction of Microglia and Macrophages in Glioblastoma: Close Relatives, Different Tasks?
Authors: Brandenburg Susan , Blank Anne , Bungert Alexander D. , Vajkoczy Peter
Published: December 2020

For decades, it has been known that the tumor microenvironment is significant for glioma progression, namely the infiltration of myeloid cells like microglia and macrophages. Hence, these cell types and their specific tasks in tumor progression are subject to ongoing research. However, the distribution of the brain resident microglia and the peripheral macrophages within the tumor tissue and their functional activity are highly debated. Results depend on the method used to discriminate between microglia and macrophages, whereby this specification is already difficult due to limited options to distinguish between these both cell populations that show mostly the same surface markers and morphology. Moreover, there are indications about various functions of microglia and macrophages but again varying on the method of discrimination. In our review, we summarize the current literature to determine which methods have been applied to differentiate the brain resident microglia from tumor-infiltrated macrophages. Furthermore, we compiled data about the proportion of microglia and macrophages in glioma tissues and ascertained if pro- or anti-tumoral effects could be allocated to one or the other myeloid cell population. Recent research made tremendous efforts to distinguish microglia from recruited macrophages. For future studies, it could be essential to verify which role these cells play in brain tumor pathology to proceed with novel immunotherapeutic strategies.
The Role of the Gut Microbiome in Liver Cirrhosis Treatment
Authors: Lee Na Young , Suk Ki Tae
Published: December 2020

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.
Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells
Authors: Olivas-Aguirre Miguel , Torres-López Liliana , Pottosin Igor , Dobrovinskaya Oxana
Published: December 2020

Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆Ψm) and [Ca2+]m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry. Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆Ψm and induced a significant [Ca2+]m increase, whereas inefficient phenols did not. Dissipation of the ∆Ψm by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca2+ uniporter, respectively. Ru360 prevented the phenol-induced [Ca2+]m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆Ψm depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death. Thus, all three phenols exert their antileukemic activity via mitochondrial Ca2+ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.
Novel Perspectives Regarding the Pathology, Inflammation, and Biomarkers of Acute Respiratory Distress Syndrome
Authors: Sivapalan Pradeesh , Bonnesen Barbara , Jensen Jens-Ulrik
Published: December 2020

Acute respiratory distress syndrome (ARDS) is an acute inflammation of the lung resulting from damage to the alveolar–capillary membrane, and it is diagnosed using a combination of clinical and physiological variables. ARDS develops in approximately 10% of hospitalised patients with pneumonia and has a mortality rate of approximately 40%. Recent research has identified several biomarkers associated with ARDS pathophysiology, and these may be useful for diagnosing and monitoring ARDS. They may also highlight potential therapeutic targets. This review summarises our current understanding of those clinical biomarkers: (1) biomarkers of alveolar and bronchiolar injury, (2) biomarkers of endothelial damage and coagulation, and (3) biomarkers for treatment responses.
Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin
Authors: Charalambous Chrysostomos , Lapka Marek , Havlickova Tereza , Syslova Kamila , Sustkova-Fiserova Magdalena
Published: December 2020

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.
Quick-Freeze, Deep-Etch Electron Microscopy Reveals the Characteristic Architecture of the Fission Yeast Spore
Authors: Tahara Yuhei O. , Miyata Makoto , Nakamura Taro
Published: December 2020

The spore of the fission yeast Schizosaccharomyces pombe is a dormant cell that is resistant to a variety of environmental stresses. The S. pombe spore is coated by a proteinaceous surface layer, termed the Isp3 layer because it comprises mainly Isp3 protein. Although thin-section electron microscopy and scanning electron microscopy have revealed the fundamental structure of the spore, its architecture remains unclear. Here we visualized S. pombe spores by using a quick-freeze replica electron microscopy (QFDE-EM) at nanometer resolution, which revealed novel characteristic structures. QFDE-EM revealed that the Isp3 layer exists as an interwoven fibrillar layer. On the spore cell membrane, many deep invaginations, which are longer than those on the vegetative cell membrane, are aligned in parallel. We also observed that during spore germination, the cell surface changes from a smooth to a dendritic filamentous structure, the latter being characteristic of vegetative cells. These findings provide significant insight into not only the structural composition of the spore, but also the mechanism underlying the stress response of the cell.
The Influence of Disorder in the Synthesis, Characterization and Applications of a Modifiable Two-Dimensional Covalent Organic Framework
Authors: Brophy Jordan , Summerfield Kyle , Yin Jiashi , Kephart Jon , Stecher Joshua , Adams Jeramie , Yanase Takashi , Brant Jason , Li-Oakey Katie , Hoberg John , Parkinson Bruce
Published: December 2020

Two-dimensional covalent organic frameworks (2D-COFs) have been of increasing interest in the past decade due to their porous structures that ideally can be highly ordered. One of the most common routes to these polymers relies on Schiff-base chemistry, i.e., the condensation reaction between a carbonyl and an amine. In this report, we elaborate on the condensation of 3,6-dibromobenzene-1,2,4,5-tetraamine with hexaketocyclohexane (HKH) and the subsequent carbonylation of the resulting COF, along with the possibility that the condensation reaction on HKH can result in a trans configuration resulting in the formation of a disordered 2D-COF. This strategy enables modification of COFs via bromine substitution reactions to place functional groups within the pores of the materials. Ion-sieving measurements using membranes from this COF, reaction of small molecules with unreacted keto groups along with modeling studies indicate disorder in the COF polymerization process. We also present a Monte Carlo simulation that demonstrates the influence of even small amounts of disorder upon both the 2D and 3D structure of the resulting COF.
Research on a Five-Axis Machining Center Worktable with Bionic Honeycomb Lightweight Structure
Authors: Hu Lai , Zha Jun , Kan Fan , Long Hao , Chen Yaolong
Published: December 2020

The processing of high-precision aerospace parts requires not only ultra-precision machine tools, but also high-efficiency processing. However, in order to realize high-efficiency processing, besides optimizing the system and process parameters, some subversive research can also be done on the machine tool structure. In this paper, the lightweight research is mainly carried out on the structure of machine tool worktable. The traditional workbench is very “heavy” and “slowness”. If the traditional workbench is subverted and reformed to reduce the weight, the processing efficiency will be improved qualitatively. Therefore, this paper studies the lightweight worktable of CFRP (carbon fiber reinforced polymer) in combination with the biological “honeycomb” shape. At first, the tensile, bending, compressive and laminar shear analysis of CFRP were carried out, and the comprehensive parameters were obtained. Simultaneously, the theoretical research and the honeycomb structure simulation and verification of CFRP worktable are carried out. The results show that the HACT (honeycomb arrangement of circular tubes) is 18.51% better than the SACT (straight arrangement of circular tubes) and 45.05% better than the OW (original worktable) by comparing and analyzing the weight of the three modes (HACT, SACT and OW). The actual weight of bionic honeycomb lightweight worktable is 1100 kg, while the simulation result is 1080.25 kg, with an error of 1.8%. Meanwhile, it is analyzed that the original workbench weight of the five-axis machining center is 2023 kg, while the simulation result is 1998.6 kg, with an error of 1.2%. The lightweight degree is reduced by 45.05%. However, the actual lightweight degree has been reduced by 45.63%. The error between simulation and actual is less than 1.3%. This kind of structural transformation has brought forward cutting-edge innovations to the machine tool processing industry. It provides a reference scheme for related enterprises in the future equipment renovation.
Influence of the β− Radiation/Cold Atmospheric-Pressure Plasma Surface Modification on the Adhesive Bonding of Polyolefins
Authors: Bednarik Martin , Mizera Ales , Manas Miroslav , Navratil Milan , Huba Jakub , Achbergerova Eva , Stoklasek Pavel
Published: December 2020

The goal of this research was to examine the effect of two surface modification methods, i.e., radiation cross-linking and plasma treatment, on the adhesive properties and the final quality of adhesive bonds of polypropylene (PP), which was chosen as the representative of the polyolefin group. Polymer cross-linking was induced by beta (accelerated electrons—β−) radiation in the following dosages: 33, 66, and 99 kGy. In order to determine the usability of β− radiation for these applications (improving the adhesive properties and adhesiveness of surface layers), the obtained results were compared with values measured on surfaces treated by cold atmospheric-pressure plasma with outputs 2.4, 4, and 8 W. The effects of both methods were compared by several parameters, namely wetting contact angles, free surface energy, and overall strength of adhesive bonds. Furthermore, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were conducted. According to our findings the following conclusion was reached; both tested surface modification methods significantly altered the properties of the specimen’s surface layer, which led to improved wetting, free surface energy, and bond adhesion. Following the β− radiation, the free surface energy of PP rose by 80%, while the strength of the bond grew in some cases by 290% in comparison with the non-treated surface. These results show that when compared with cold plasma treatment the beta radiation appears to be an effective tool capable of improving the adhesive properties and adhesiveness of PP surface layers.
Anomalous Properties of the Dislocation-Free Interface between Si(111) Substrate and 3C-SiC(111) Epitaxial Layer
Authors: Kukushkin Sergey A. , Osipov Andrey V.
Published: December 2020

Thin films of single-crystal silicon carbide of cubic polytype with a thickness of 40–100 nm, which were grown from the silicon substrate material by the method of coordinated substitution of atoms by a chemical reaction of silicon with carbon monoxide CO gas, have been studied by spectral ellipsometry in the photon energy range of 0.5–9.3 eV. It has been found that a thin intermediate layer with the dielectric constant corresponding to a semimetal is formed at the 3C-SiC(111)/Si(111) interface. The properties of this interface corresponding to the minimum energy have been calculated using quantum chemistry methods. It has turned out that silicon atoms from the substrate are attracted to the interface located on the side of the silicon carbide (SiC) film. The symmetry group of the entire system corresponds to P3m1. The calculations have shown that Si atoms in silicon carbide at the interface, which are the most distant from the Si atoms of the substrate and do not form a chemical bond with them (there are only 12% of them), provide a sharp peak in the density of electronic states near the Fermi energy. As a result, the interface acquires semimetal properties that fully correspond to the ellipsometry data.
Corrosion Resistance of the CpTi G2 Cellular Lattice with TPMS Architecture for Gas Diffusion Electrodes
Authors: Łosiewicz Bożena , Maszybrocka Joanna , Kubisztal Julian , Skrabalak Grzegorz , Stwora Andrzej
Published: December 2020

The corrosion of materials used in the design of metal-air batteries may shorten their cycle life. Therefore, metal-based materials with enhanced electrochemical stability have attracted much attention. The purpose of this work was to determine the corrosion resistance of commercially pure titanium Grade 2 (CpTi G2) cellular lattice with the triply periodic minimal surfaces (TPMS) architecture of G80, D80, I-2Y80 in 0.1 M KOH solution saturated with oxygen at 25 °C. To produce CpTi G2 cellular lattices, selective laser melting technology was used which allowed us to obtain 3D cellular lattice structures with a controlled total porosity of 80%. For comparison, the bulk electrode was also investigated. SEM examination and statistical analysis of the surface topography maps of the CpTi G2 cellular lattices with the TPMS architecture revealed much more complex surface morphology compared to the bulk CpTi SLM. Corrosion resistance tests of the obtained materials were conducted using open circuit potential method, Tafel curves, anodic polarization curves, and electrochemical impedance spectroscopy. The highest corrosion resistance and the lowest material consumption per year were revealed for the CpTi G2 cellular lattice with TPMS architecture of G80, which can be proposed as promising material with increased corrosion resistance for gas diffusion in alkaline metal-air batteries.
Standoff Distance in Ultrasonic Pulsating Water Jet
Authors: Srivastava Madhulika , Nag Akash , Chattopadhyaya Somnath , Hloch Sergej
Published: December 2020

The water hammer effect is the basis of technologies which is artificially responsible for the decay of continuous jets. A recently developed technique enhances the pressure fluctuations using an acoustic chamber, leading to enhanced erosion effects for various water volume flow rates. The optimum standoff distance for an ultrasonic enhanced water jet is not appropriately estimated using an inclined trajectory. The objective of this study is to comprehend the true nature of the interaction of the standoff distance following the stair trajectory and traverse speed of the nozzle on the erosion depth. Additionally, it also critically compares the new method (staircase trajectory) that obeys the variation in frequency of the impingements for defined volume flow rates with the inclined trajectory. In this study, at constant pressure (p = 70 MPa), the role of impingement distribution with the variation of traverse speed (v = 5–35 mm/s) along the centerline of the footprint was investigated. The maximum erosion depth corresponding to each traverse speed is observed at approximately same standoff distance (65 ± 5 mm) and decreases with the increment in traverse speed (h = 1042 and 47 µm at v = 5 and 35 mm/s, respectively). The results are attributed to the variation in the number of impingements per unit length. The surface and morphology analysis of the cross-section using SEM manifested the presence of erosion characteristics (micro-cracks, cavities, voids, and upheaved surface). By varying the water cluster, different impingement densities can be achieved that are suitable for technological operations such as surface peening, material disintegration, or surface roughening.
Microstructure and Properties of As-Cast and Heat-Treated 2017A Aluminium Alloy Obtained from Scrap Recycling
Authors: Grażyna Mrówka-Nowotnik , Gancarczyk Kamil , Nowotnik Andrzej , Dychtoń Kamil , Boczkal Grzegorz
Published: December 2020

The continuous increase in the consumption of aluminium and its alloys has led to an increase in the amount of aluminium scrap. Due to environmental protection, and to reduce the costs of manufacturing aluminum in recent years, a lot of research is devoted to recycling of aluminum alloys. The paper presents the results of research concerning the possibility of manufacturing standardized alloy 2017A from commercial and post-production scrap by continuous casting. Obtained from recycling process ingots were subjected to analysis of chemical composition and intermetallic phase composition. Based on the results of light microscopy (LM), scanning electron microscopy + electron dispersive spectroscopy (SEM + EDS), and X-ray diffraction (XRD) the following phases in the as-cast state were identified: θ-Al2Cu, β-Mg2Si, Al7Cu2Fe, Q-Al4Cu2Mg8Si7, and α-Al15(FeMn)3(SiCu)2. During solution heat treatment most of the primary precipitates of intermetallic phases, like θ-Al2Cu, β-Mg2Si, and Q-Al4Cu2Mg8Si7, were dissolved in the solid solution α-Al, and during natural and artificial aging they precipitate as strengthening phases θ-Al2Cu and Q-Al4Cu2Mg8Si7 with high dispersion. The highest hardness—150.3 HB—of 2017A alloy was obtained after solution heat treatment from 510 °C and aging at 175 °C. In the static tensile test the mechanical (Rm and Rp0.2) and plastic (A5) properties were determined for 2017A alloy in the cast state and after T4 heat treatment. The highest strength properties—tensile strength Rm = 450.5 MPa and yield strength R0.2 = 268.7 MPa with good relative elongation A5 = 14.65%, were obtained after solution heat treatment at 510 °C/6 h/water quenching and natural aging at 25 °C for 70 h. The alloy manufactured from recycled scrap is characterized by relatively high mechanical properties.
Billet Straightening by Three-Point Bending and Its Automation
Authors: Halama Radim , Sikora Jan , Fusek Martin , Mec Jaromír , Bartecká Jana , Wagnerová Renata
Published: December 2020

This paper presents the current results of cooperation focused on automatic billet straightening machine development. First, an experimental study of three-point bending realized on small specimens is presented to explain the basic ideas of the straightening. Then, the main regimes of straightening and the algorithm itself are described together. Subsequent finite element simulations of operational experiments show the applicability of the developed theory. The significance of material parameters estimation is depicted in this work. At least four parameters have to be properly determined for a new material in the straightening process.
Experimental Study on Dynamic Splitting Characteristics of Carbon Fiber Reinforced Concrete
Authors: Chen Zhan-Yang , Yang Jun
Published: December 2020

Due to the non-uniform tension and compression strength of concrete, carbon fiber can be added to concrete to improve its static tensile behavior and increase the tension–compression ratio. In view of the destructive consequences of impacts and explosions, it is necessary to study the dynamic responses of carbon fiber reinforced concrete (CFRC) structures. Therefore, the effects of the stress rates and carbon fiber contents on the dynamic tension behavior of CFRC were investigated in this paper. The dynamic splitting tests of concrete with the fiber contents of 0, 0.1, 0.2, and 0.3% were carried out by using a split Hopkinson pressure bar (SHPB) device with a diameter of 74 mm. We found that with the increase of fiber content, the static tensile strength of CFRC increases obviously, but the increased amplitude tends to decrease. The dynamic tensile strength and dynamic increase factor (DIF) both increase with the increase of stress rate, but the growth rate slows down, showing an obvious rate effect. The rate sensitivity of ordinary concrete is higher than CFRC. There are significant differences in the influence of carbon fiber on the dynamic and static strength of concrete. In the design of concrete mixing proportion, the content of carbon fiber should be appropriately selected to meet the requirements of dynamic and static mechanical properties.
FGF-23 and Phosphate in Children with Chronic Kidney Disease: A Cross-Sectional Study in Kazakhstan
Authors: Balmukhanova Altynay , Kabulbayev Kairat , Alpay Harika , Kanatbayeva Assiya , Balmukhanova Aigul
Published: December 2020

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.
Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation
Authors: Apostu Raluca-Cristina , Fagarasan Vlad , Ciuce Catalin C. , Drasovean Radu , Gheban Dan , Scurtu Radu Razvan , Grama Alina , Stefanescu Ana Cristina , Ciuce Constantin , Pop Tudor Lucian
Published: December 2020

Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1–4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice’s clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection.
N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents
Authors: Sabbah Dima A. , Haroon Rawan A. , Bardaweel Sanaa K. , Hajjo Rima , Sweidan Kamal
Published: December 2020

Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR (1H and 13C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC50 µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues.
Evidence for Phytoremediation and Phytoexcretion of NTO from Industrial Wastewater by Vetiver Grass
Authors: RoyChowdhury Abhishek , Mukherjee Pallabi , Panja Saumik , Datta Rupali , Christodoulatos Christos , Sarkar Dibyendu
Published: December 2020

The use of insensitive munitions such as 3-nitro-1,2,4-triazol-5-one (NTO) is rapidly increasing and is expected to replace conventional munitions in the near future. Various NTO treatment technologies are being developed for the treatment of wastewater from industrial munition facilities. This is the first study to explore the potential phytoremediation of industrial NTO-wastewater using vetiver grass (Chrysopogon zizanioides L.). Here, we present evidence that vetiver can effectively remove NTO from wastewater, and also translocated NTO from root to shoot. NTO was phytotoxic and resulted in a loss of plant biomass and chlorophyll. The metabolomic analysis showed significant differences between treated and control samples, with the upregulation of specific pathways such as glycerophosphate metabolism and amino acid metabolism, providing a glimpse into the stress alleviation strategy of vetiver. One of the mechanisms of NTO stress reduction was the excretion of solid crystals. Scanning electron microscopy (SEM), electrospray ionization mass spectrometry (ESI-MS), and Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of NTO crystals in the plant exudates. Further characterization of the exudates is in progress to ascertain the purity of these crystals, and if vetiver could be used for phytomining NTO from industrial wastewater.
Discovery of Monoacylglycerol Lipase (MAGL) Inhibitors Based on a Pharmacophore-Guided Virtual Screening Study
Authors: Jha Vibhu , Biagi Marzia , Spinelli Valeria , Di Stefano Miriana , Macchia Marco , Minutolo Filippo , Granchi Carlotta , Poli Giulio , Tuccinardi Tiziano
Published: December 2020

Monoacylglycerol lipase (MAGL) is an important enzyme of the endocannabinoid system that catalyzes the degradation of the major endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL is associated with pathological conditions such as pain, inflammation and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. Furthermore, elevated levels of MAGL have been found in aggressive breast, ovarian and melanoma cancer cells. Due to its different potential therapeutic implications, MAGL is considered as a promising target for drug design and the discovery of novel small-molecule MAGL inhibitors is of great interest in the medicinal chemistry field. In this context, we developed a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations, which showed a final hit rate of 50% validating the reliability of the in silico workflow and led to the identification of two promising and structurally different reversible MAGL inhibitors, VS1 and VS2. These ligands represent a valuable starting point for structure-based hit-optimization studies aimed at identifying new potent MAGL inhibitors.
TiCl4 Dissolved in Ionic Liquid Mixtures from Аb Initio Molecular Dynamics Simulations
Authors: Esser Lars , Macchieraldo Roberto , Elfgen Roman , Sieland Melanie , Smarsly Bernd Michael , Kirchner Barbara
Published: December 2020

To gain a deeper understanding of the TiCl4 solvation effects in multi-component ionic liquids, we performed ab initio molecular dynamics simulations of 1-butyl-3-methylimidazolium [C4C1Im]+, tetrafluoroborate [BF4]−, chloride [Cl]− both with and without water and titanium tetrachloride TiCl4. Complex interactions between cations and anions are observed in all investigated systems. By further addition of water and TiCl4 this complex interaction network is extended. Observations of the radial distribution functions and number integrals show that water and TiCl4 not only compete with each other to interact mainly with [Cl]−, which strongly influences the cation-[BF4]− interaction, but also interact with each other, which leads to the fact that in certain systems the cation-anion interaction is enhanced. Further investigations of the Voronoi polyhedra analysis have demonstrated that water has a greater impact on the nanosegregated system than TiCl4 which is also due to the fact of the shear amount of water relative to all other components and its higher mobility compared to TiCl4. Overall, the polar network of the IL mixture collapses by including water and TiCl4. In the case of [Cl]− chloride enters the water continuum, while [BF4]− remains largely unaffected, which deeply affects the interaction of the ionic liquid (IL) network.
Designing New Antibacterial Wound Dressings: Development of a Dual Layer Cotton Material Coated with Poly(Vinyl Alcohol)_Chitosan Nanofibers Incorporating Agrimonia eupatoria L. Extract
Authors: Mouro Cláudia , Dunne Colum P. , Gouveia Isabel C.
Published: December 2020

Wounds display particular vulnerability to microbial invasion and infections by pathogenic bacteria. Therefore, to reduce the risk of wound infections, researchers have expended considerable energy on developing advanced therapeutic dressings, such as electrospun membranes containing antimicrobial agents. Among the most used antimicrobial agents, medicinal plant extracts demonstrate considerable potential for clinical use, due primarily to their efficacy allied to relatively low incidence of adverse side-effects. In this context, the present work aimed to develop a unique dual-layer composite material with enhanced antibacterial activity derived from a coating layer of Poly(vinyl alcohol) (PVA) and Chitosan (CS) containing Agrimonia eupatoria L. (AG). This novel material has properties that facilitate it being electrospun above a conventional cotton gauze bandage pre-treated with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical (TEMPO). The produced dual-layer composite material demonstrated features attractive in production of wound dressings, specifically, wettability, porosity, and swelling capacity. Moreover, antibacterial assays showed that AG-incorporated into PVA_CS’s coating layer could effectively inhibit Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) growth. Equally important, the cytotoxic profile of the dual-layer material in normal human dermal fibroblast (NHDF) cells demonstrated biocompatibility. In summary, these data provide initial confidence that the TEMPO-oxidized cotton/PVA_CS dressing material containing AG extract demonstrates adequate mechanical attributes for use as a wound dressing and represents a promising approach to prevention of bacterial wound contamination.
Health Benefits and Chemical Composition of Matcha Green Tea: A Review
Authors: Kochman Joanna , Jakubczyk Karolina , Antoniewicz Justyna , Mruk Honorata , Janda Katarzyna
Published: December 2020

Japanese matcha is a type of powdered green tea, grown in a traditional way. Shading of the plants during the growth period enhances the processes of synthesis and accumulation of biologically active compounds, including theanine, caffeine, chlorophyll and various types of catechins. Green tea contains four main catechins, i.e., (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG), of which the latter is the most active and abundant and matcha is their best condensed source. Due to its unique chemical composition and prized flavour, which sets it apart from other tea beverages, it is considered the highest quality tea. Its health-promoting properties are attributed to the high content of antioxidant and anti-inflammatory substances. Studies confirming the high antioxidant potential of tea beverages claim that it originates from the considerable content of catechins, a type of phenolic compound with beneficial effects on human health. Due to its potential for preventing many diseases and supporting cognitive function, regular consumption of matcha may have a positive effect on both physical and mental health. The aim of this review was to compile the health benefits of matcha tea. It is the first such review to be undertaken, and presents its main bioactive compounds in a systematic manner.
Recent Advances on the Anticancer Properties of Saffron (Crocus sativus L.) and Its Major Constituents
Authors: Lambrianidou Andromachi , Koutsougianni Fani , Papapostolou Irida , Dimas Konstantinos
Published: December 2020

Cancer is the second leading cause of death globally with an estimated 9.6 million deaths in 2018 and a sustained rise in its incidence in both developing and developed countries. According to the WHO, about 1 in 6 deaths is due to cancer. Despite the emergence of many pioneer therapeutic options for patients with cancer, their efficacy is still time-limited and noncurative. Thus, continuous intensive screening for superior and safer drugs is still ongoing and has resulted in the detection of the anticancer properties of several phytochemicals. Among the spices, Crocus sativus L. (saffron) and its main constituents, crocin, crocetin, and safranal, have attracted the interest of the scientific community. Pharmacological experiments have established numerous beneficial properties for this brilliant reddish-orange dye derived from the flowers of a humble crocus family species. Studies in cultured human malignant cell lines and animal models have demonstrated the cancer prevention and antitumor activities of saffron and its main ingredients. This review provides an insight into the advances in research on the anticancer properties of saffron and its components, discussing preclinical data, clinical trials, and patents aiming to improve the pharmacological properties of saffron and its major ingredients.
Terpyridine-Functionalized Calixarenes: Synthesis, Characterization and Anion Sensing Applications
Authors: Edwards Nicola Y. , Schnable David M. , Gearba-Dolocan Ioana R. , Strubhar Jenna L.
Published: December 2020

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb3+ and Eu3+. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (1H and 13C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.
Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy
Authors: Kusama Kazuya , Miyagawa Mayuko , Ota Koichiro , Kuwabara Naoko , Saeki Kaori , Ohnishi Yuki , Kumaki Yasuhiro , Aizawa Tomoyasu , Nakasone Toyokazu , Okamatsu Shigemi , Miyaoka Hiroaki , Tamura Kazuhiro
Published: December 2020

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.
Predefined Diets in Patients with Inflammatory Bowel Disease: Systematic Review and Meta-Analysis
Authors: Comeche José M. , Gutierrez-Hervás Ana , Tuells José , Altavilla Cesare , Caballero Pablo
Published: December 2020

Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and characterized by the importance of diet in pathological development. This study aims to understand how the use of predefined diets can affect the adult population diagnosed with IBD. We conducted a systematic review and meta-analysis. From the different databases (MEDLINE, Scopus, Cochrane, LILACS, CINAHL, and WOS), we found 4195 registers. After a review process, only 31 research studies were selected for qualitative synthesis and 10 were selected for meta-analysis. The variables used were Crohn’s Disease Activity Index (CDAI) for patients with Crohn’s Disease (CD) and fecal calprotectin (FC), C-Reactive Protein (CRP), and albumin (ALB) for patients with IBD. Predefined diets have been shown to have partial efficacy for the treatment of IBD and are compatible with other medical treatments. CDAI improved but with reasonable doubts due to the high heterogeneity of the data, while no differences were observed for ALB, FC, and CRP. More studies that evaluate the influence of predefined diets on IBD patients are needed due to the great variability in diets and the tools used to measure their effects.
Comparison of Chemical Composition and Biological Activities of Eight Selaginella Species
Authors: Křížkovská Bára , Kumar Rohitesh , Řehořová Kateřina , Sýkora David , Dobiasová Simona , Kučerová Denisa , Tan Maria Carmen , Linis Virgilio , Oyong Glenn , Ruml Tomáš , Lipov Jan , Viktorová Jitka
Published: December 2020

Selaginella P. Beauv. is a group of vascular plants in the family Selaginellaceae Willk., found worldwide and numbering more than 700 species, with some used as foods and medicines. The aim of this paper was to compare methanolic (MeOH) and dichloromethane (DCM) extracts of eight Selaginella species on the basis of their composition and biological activities. Six of these Selaginella species are underinvestigated. Using ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) analysis, we identified a total of 193 compounds among the tested Selaginella species, with flavonoids predominating. MeOH extracts recovered more constituents that were detected, including selaginellins, the occurrence of which is only typical for this plant genus. Of all the tested species, Selaginellaapoda contained the highest number of identified selaginellins. The majority of the compounds were identified in S. apoda, the fewest compounds in Selaginellacupressina. All the tested species demonstrated antioxidant activity using oxygen radical absorption capacity (ORAC) assay, which showed that MeOH extracts had higher antioxidant capacity, with the half maximal effective concentration (EC50) ranging from 12 ± 1 (Selaginellamyosuroides) to 124 ± 2 (Selaginellacupressina) mg/L. The antioxidant capacity was presumed to be correlated with the content of flavonoids, (neo)lignans, and selaginellins. Inhibition of acetylcholinesterase (AChE) was mostly discerned in DCM extracts and was only exhibited in S. myosuroides, S. cupressina, Selaginellabiformis, and S. apoda extracts with the half maximal inhibitory concentration (IC50) in the range of 19 ± 3 to 62 ± 1 mg/L. Substantial cytotoxicity against cancer cell lines was demonstrated by the MeOH extract of S. apoda, where the ratio of the IC50 HEK (human embryonic kidney) to IC50 HepG2 (hepatocellular carcinoma) was 7.9 ± 0.2. MeOH extracts inhibited the production of nitrate oxide and cytokines in a dose-dependent manner. Notably, S. biformis halved the production of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 at the following concentrations: 105 ± 9, 11 ± 1, and 10 ± 1 mg/L, respectively. Our data confirmed that extracts from Selaginella species exhibited cytotoxicity against cancer cell lines and AChE inhibition. The activity observed in S. apoda was the most promising and is worth further exploration.