bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering the Core Microbiome and Distribution of Palmerolide in Synoicum adareanum Across the Anvers Island Archipelago, Antarctica
Authors: Murray Alison E. , Avalon Nicole E. , Bishop Lucas , Davenport Karen W. , Delage Erwan , Dichosa Armand E.K. , Eveillard Damien , Higham Mary L. , Kokkaliari Sofia , Lo Chien-Chi , Riesenfeld Christian S. , Young Ryan M. , Chain Patrick S.G. , Baker Bill J.
Published: June 2020

Polar marine ecosystems hold the potential for bioactive compound biodiscovery, based on their untapped macro- and microorganism diversity. Characterization of polar benthic marine invertebrate-associated microbiomes is limited to few studies. This study was motivated by our interest in better understanding the microbiome structure and composition of the ascidian, Synoicum adareanum, in which palmerolide A (PalA), a bioactive macrolide with specificity against melanoma, was isolated. PalA bears structural resemblance to a hybrid nonribosomal peptide-polyketide that has similarities to microbially-produced macrolides. We conducted a spatial survey to assess both PalA levels and microbiome composition in S. adareanum in a region of the Antarctic Peninsula near Anvers Island (64°46′ S, 64°03′ W). PalA was ubiquitous and abundant across a collection of 21 ascidians (3 subsamples each) sampled from seven sites across the Anvers Island Archipelago. The microbiome composition (V3–V4 16S rRNA gene sequence variants) of these 63 samples revealed a core suite of 21 bacterial amplicon sequence variants (ASVs)—20 of which were distinct from regional bacterioplankton. ASV co-occurrence analysis across all 63 samples yielded subgroups of taxa that may be interacting biologically (interacting subsystems) and, although the levels of PalA detected were not found to correlate with specific sequence variants, the core members appeared to occur in a preferred optimum and tolerance range of PalA levels. These results, together with an analysis of the biosynthetic potential of related microbiome taxa, describe a conserved, high-latitude core microbiome with unique composition and substantial promise for natural product biosynthesis that likely influences the ecology of the holobiont.
Petrogenesis and Geochronology of Tianshui Granites from Western Qinling Orogen, Central China: Implications for Caledonian and Indosinian Orogenies on the Asian Plate
Authors: Mughal Muhammad Saleem , Zhang Chengjun , Hussain Amjad , Rehman Hafiz Ur , Du Dingding , Baig Mirza Shahid , Basharat Muhammad , Zhang Jingya , Zheng Qi , Hussain Syed Asim
Published: June 2020

The precise timing, petrogenesis, and geodynamic significance of three granitoid bodies (Beidao granite, Caochuanpu granite, Yuanlongzhen granite, and the Roche type rock) of the Tianshui area in the Western Qinling Orogen, central China, are poorly constrained. We performed an integrated study of petrology, geochemistry, and zircon U-Pb dating to constrain their genesis and tectonic implication. Petrographic investigation of the granites shows that the rocks are mainly monzogranites. The Al saturation index (A/CNK versus SiO2) of the granitoid samples indicates meta-aluminous to peraluminous I-type granites. Their magmas were likely generated by the partial melting of igneous protoliths during the syn-collisional tectonic regime. Rare-earth-elements data further support their origin from a magma that was formed by the partial melting of lower continental crust. The Beidao, Caochuanpu, and Yuanlongzhen granites yielded U-Pb zircon weighted mean ages of 417 ± 5 Ma, 216 ± 3 Ma, and 219 ± 3 Ma, respectively. This study shows that the Beidao granite possibly formed in syn- to post-collision tectonic settings due to the subduction of the Proto-Tethys under the North China Block, and can be linked to the generally reported Caledonian orogeny (440–400 Ma) in the western segment of the North Qinling belt, whereas Yuanlongzhen and Caochuanpu granites can be linked to the widely known Indosinian orogeny (255–210 Ma). These granitoids formed due to the subduction of the oceanic lithospheres of the Proto-Tethyan Qinling and Paleo-Tethyan Qinling. The Roche type rock, tourmaline-rich, was possibly formed from the hydrothermal fluids as indicated by the higher concentrations of boron leftover during the late-stages of magmatic crystallization of the granites.
Reutilization Prospects of Diamond Clay Tailings at the Lomonosov Mine, Northwestern Russia
Authors: Pashkevich Mariya , Alekseenko Alexey
Published: June 2020

Approaches to reutilization of diamond clay tailings in northern environments are considered in the example of the Subarctic region of Russia. The monitoring studies are conducted at storage facilities of Severalmaz PJSC where ca. 14 million cubic meters of waste rock are produced annually after kimberlite mining and processing. The tailings of diamond ore dressing waste are situated in complex geological conditions of high-groundwater influx and harsh cold climate with low levels of solar radiation and the average annual temperature below freezing point. Furthermore, the adjoining protected forests with a significant diversity of biogeocenoses and salmon-spawning rivers are affected by the storage area. Reducing the impact of the tailings can be achieved through the reuse of the stored clay magnesia rocks obtained from saponite-containing suspension. The experiments reveal the most promising ways of their application as potential secondary mineral raw materials: cement clinker and ceramics manufacture, integration of alkaline clay into the reclamation of acidic peat bogs, and production of aqueous clay-based drilling fluid. Field and laboratory tests expose the advantages and prospects of each suggested treatment technique.
Unsaturated Response of Clayey Soils Stabilised with Alkaline Cements
Authors: Araújo Nuno , Corrêa-Silva Manuela , Miranda Tiago , Topa Gomes António , Castro Fernando , Teixeira Tiago , Cristelo Nuno
Published: June 2020

The influence of suction on the mechanical behaviour of unsaturated chemically stabilised soils is still mostly unknown and unquantified. This is also motivated by the difficulties associated with the experimental procedure required to fully characterise the unsaturated response of the soil, including its direct influence on traditional strength tests. The present paper presents the soil water retention curves obtained for a Portuguese soil before and after being stabilised with Portland cement (OPC) and an alkali-activated cement (AAC). Saturated undrained triaxial tests were also performed for the same curing conditions (0, 28, and 90 days). Previous attempts to characterise the retention curve of soils stabilised with AAC are unknown, and the results showed that the pore volume structure is already formed after 28 days, prior to the full development of the gel matrix responsible for the strength increase between 28 and 90 days. The curve changed after stabilisation, and with each binder, as the OPC presented a higher air-entry value and a narrower suction range compared to the AAC solution. The significant differences between the curves obtained from each binder suggest the future development of a methodology to assess the quality of the AAC stabilisation.
Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
Authors: Al Kury Lina Tariq , Dayyan Fazli , Ali Shah Fawad , Malik Zulkifal , Khalil Atif Ali Khan , Alattar Abdullah , Alshaman Reem , Ali Amjad , Khan Zahid
Published: June 2020

Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All these injury markers contributed to a significant release of apoptotic (caspase-3 and c-Jun N-terminal kinases (JNK)) and tumor necrosis factor (TNF-α)-like inflammatory mediators. Treatment with Gb counteracts MTX-mediated apoptosis and inflammation dose-dependently along with modulating the innate antioxidative mechanisms such as glutathione (GSH) and glutathione S-transferase (GST). These results were further supplemented by in silico study to analyze drug-receptor interactions (for several Gb constituents and target proteins) stabilized by a low energy value and with a good number of hydrogen bonds. These findings demonstrated that Gb could ameliorate MTX-induced elevated liver reactive oxygen species (ROS) and inflammation, possibly by JNK and TNF-α modulation.
N-Alkylaminoferrocene-Based Prodrugs Targeting Mitochondria of Cancer Cells
Authors: Reshetnikov Viktor , Özkan Hülya Gizem , Daum Steffen , Janko Christina , Alexiou Christoph , Sauer Caroline , Heinrich Markus R. , Mokhir Andriy
Published: June 2020

Intracellular concentration of reactive oxygen species (e.g., H2O2) in cancer cells is elevated over 10-fold as compared to normal cells. This feature has been used by us and several other research groups to design cancer specific prodrugs, for example, N-alkylaminoferrocene (NAAF)-based prodrugs. Further improvement of the efficacy of these prodrugs can be achieved by their targeting to intracellular organelles containing elevated reactive oxygen species (ROS) amounts. For example, we have previously demonstrated that lysosome-targeted NAAF-prodrugs exhibit higher anticancer activity in cell cultures, in primary cells and in vivo (Angew. Chem. Int. Ed. 2017, 56, 15545). Mitochondrion is an organelle, where electrons can leak from the respiratory chain. These electrons can combine with O2, generating O2−• that is followed by dismutation with the formation of H2O2. Thus, ROS can be generated in excess in mitochondria and targeting of ROS-sensitive prodrugs to these organelles could be a sensible possibility for enhancing their efficacy. We have previously reported on NAAF-prodrugs, which after their activation in cells, are accumulated in mitochondria (Angew. Chem. Int. Ed. 2018, 57, 11943). Now we prepared two hybrid NAAF-prodrugs directly accumulated in mitochondria and activated in these organelles. We studied their anticancer activity and mode of action. Based on these data, we concluded that ROS produced by mitochondria is not available in sufficient quantities for activation of the ROS-responsive prodrugs. The reason for this can be efficient scavenging of ROS by antioxidants. Our data are important for the understanding of the mechanism of action of ROS-activatable prodrugs and will facilitate their further development.
Magnetic Elements for Neuromorphic Computing
Authors: Blachowicz Tomasz , Ehrmann Andrea
Published: June 2020

Neuromorphic computing is assumed to be significantly more energy efficient than, and at the same time expected to outperform, conventional computers in several applications, such as data classification, since it overcomes the so-called von Neumann bottleneck. Artificial synapses and neurons can be implemented into conventional hardware using new software, but also be created by diverse spintronic devices and other elements to completely avoid the disadvantages of recent hardware architecture. Here, we report on diverse approaches to implement neuromorphic functionalities in novel hardware using magnetic elements, published during the last years. Magnetic elements play an important role in neuromorphic computing. While other approaches, such as optical and conductive elements, are also under investigation in many groups, magnetic nanostructures and generally magnetic materials offer large advantages, especially in terms of data storage, but they can also unambiguously be used for data transport, e.g., by propagation of skyrmions or domain walls. This review underlines the possible applications of magnetic materials and nanostructures in neuromorphic systems.
A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity
Authors: Alcântara Laura M. , Ferreira Thalita C. S. , Fontana Vanessa , Chatelain Eric , Moraes Carolina B. , Freitas-Junior Lucio H.
Published: June 2020

High genetic and phenotypic variability between Leishmania species and strains within species make the development of broad-spectrum antileishmanial drugs challenging. Thus, screening panels consisting of several diverse Leishmania species can be useful in enabling compound prioritization based on their spectrum of activity. In this study, a robust and reproducible high content assay was developed, and 1280 small molecules were simultaneously screened against clinically relevant cutaneous and visceral species: L. amazonensis, L. braziliensis, and L. donovani. The assay is based on THP-1 macrophages infected with stationary phase promastigotes and posterior evaluation of both compound antileishmanial activity and host cell toxicity. The profile of compound activity was species-specific, and out of 51 active compounds, only 14 presented broad-spectrum activity against the three species, with activities ranging from 52% to 100%. Notably, the compounds CB1954, Clomipramine, Maprotiline, Protriptyline, and ML-9 presented pan-leishmanial activity, with efficacy greater than 70%. The results highlight the reduced number of compound classes with pan-leishmanial activity that might be available from diversity libraries, emphasizing the need to screen active compounds against a panel of species and strains. The assay reported here can be adapted to virtually any Leishmania species without the need for genetic modification of parasites, providing the basis for the discovery of broad spectrum anti-leishmanial agents.
The Use of Macro, Micro, and Trace Elemental Profiles to Differentiate Commercial Single Vineyard Pinot noir Wines at a Sub-Regional Level
Authors: Tanabe Courtney K. , Nelson Jenny , Boulton Roger B. , Ebeler Susan E. , Hopfer Helene
Published: June 2020

The compositional authentication of wine is of great interest, as the geographic origin of the grapes is often associated with quality, uniqueness, and authenticity. Previous elemental fingerprinting studies mainly discriminated wines from different countries or regions within a country. Here, we report the use of element profiles to distinguish commercial Pinot noir wines from five sub-regional appellations or neighborhoods within one American viticultural area (AVA). Fifty-three single cultivar wines were collected over two harvests and analyzed using microwave plasma-atomic emission spectroscopy (MP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). Of 62 monitored elements that were quantified with fully validated methods, 24 and 32 elements differed significantly across the neighborhoods and vintages, respectively (p < 0.05). Targeted canonical variate analysis (CVA) explained 85%-90% of the variance ratio across the two vintages, indicating persistent and stable elemental fingerprints of wines at a sub-regional level. A sixth, newly founded neighborhood was correctly grouped separately from the others using a Soft Independent Modeling of Class Analogy (SIMCA), indicating the potential of elemental fingerprints for wine authenticity.
Transiently Expressed Mistletoe Lectin II in Nicotiana benthamiana Demonstrates Anticancer Activity In Vitro
Authors: Mazalovska Milena , Kouokam J. Calvin
Published: June 2020

Mistletoe (Viscum album) extracts have been used as alternative and complementary therapeutic preparations in multiple cancers for decades. Mistletoe lectins (ML-I, ML-II, and ML-III) are considered to be the main anticancer components of such preparations. In the present study, ML-II was transiently expressed in Nicotiana benthamiana using the pEAQ-HT expression system. Expression levels of up to 60 mg/kg of the infiltrated plant tissue were obtained, and a three-fold increase was achieved by adding the endoplasmic reticulum (ER) retention signal KDEL to the native ML-II sequence. The native protein containing His-tag and KDEL was purified by immobilized metal affinity chromatography (IMAC) and gel filtration. We found that the recombinant ML-II lectin was glycosylated and retained its carbohydrate-binding activity. In addition, we demonstrated that plant produced ML-II displayed anticancer activity in vitro, inhibiting non-small cell lung cancer H460 and A549 cells with EC50 values of 4 and 3.5 µg/mL, respectively. Annexin V-448A and PI double staining revealed that cell cytotoxicity occurred via apoptosis induction. These results indicate that ML-II transiently expressed in N. benthamiana plants is a promising candidate as an anticancer agent, although further optimization of production and purification methods is required to enable further in vitro testing, as well as in vivo assays.
Anion Inhibition Studies of the Beta-Carbonic Anhydrase from Escherichia coli
Authors: Del Prete Sonia , De Luca Viviana , Nocentini Alessio , Scaloni Andrea , Mastrolorenzo Margaret D. , Supuran Claudiu T. , Capasso Clemente
Published: June 2020

The interconversion of CO2 and HCO3− is catalyzed by a superfamily of metalloenzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1), which maintain the equilibrium between dissolved inorganic CO2 and HCO3−. In the genome of Escherichia coli, a Gram-negative bacterium typically colonizing the lower intestine of warm-blooded organisms, the cyn operon gene includes the CynT gene, encoding for a β-CA, and CynS gene, encoding for the cyanase. CynT (β-CA) prevents the depletion of the cellular bicarbonate, which is further used in the reaction catalyzed by cyanase. A second β-CA (CynT2 or Can or yadF), as well as a γ and ι-CAs were also identified in the E. coli genome. CynT2 is essential for bacterial growth at atmospheric CO2 concentration. Here, we characterized the kinetic properties and the anion inhibition profiles of recombinant CynT2. The enzyme showed a good activity for the physiological CO2 hydratase reaction with the following parameters: kcat = 5.3 × 105 s−1 and kcat/KM = of 4.1 × 107 M−1 s−1. Sulfamide, sulfamate, phenylboronic acid, phenylarsonic acid, and diethyldithiocarbamate were the most effective CynT2 inhibitors (KI = 2.5 to 84 µM). The anions allowed for a detailed understanding of the interaction of inhibitors with the amino acid residues surrounding the catalytic pocket of the enzyme and may be used as leads for the design of more efficient and specific inhibitors.
Synthesis, Molecular Recognition Study and Liquid Membrane-Based Applications of Highly Lipophilic Enantiopure Acridino-Crown Ethers
Authors: Golcs Ádám , Ádám Bálint Árpád , Horváth Viola , Tóth Tünde , Huszthy Péter
Published: June 2020

New highly lipophilic enantiopure crown ethers containing a heterocyclic unit have been synthesized. Phase transport, UV-Vis- and fluorescence spectrophotometric investigations as well as electrochemical studies on the complexation of the new macrocycles with several amine and amino acid derivatives were also carried out. Achiral amines were used for studying the structural preference of the new macrocycles. Among the studied structural features of the guest molecules, the intermolecular π-π interaction showed the most significant effect on complexation, which made the aralkylamine-type compounds the most preferable guest molecules. The studied liquid membrane-based applications and photophysical investigations showed appreciable enantiomeric recognition toward some aralkylamine model compounds with homochiral preferences. New crown ether derivatives (R,R)-2 and (S,S)-2 were successfully applied as enantioselective carrier and sensor molecules.
Liquid Crystalline Copolymers Containing Sulfonic and Light-Responsive Groups: From Molecular Design to Conductivity
Authors: Mohd Alauddin Sakinah , Fadhilah Kamalul Aripin Nurul , Selvi Velayutham Thamil , Martinez-Felipe Alfonso
Published: June 2020

In the search for novel smart multifunctional liquid crystalline materials, we report the synthesis, thermal and structural characterisation, and the conductivity, of a set of new block and statistical copolymers, containing light-responsive mesogenic groups (MeOAzB), polar sulfonic acids (AMPS), and methyl(methacrylate) groups (MMA). By using a cascade of reversible addition-fragmentation chain polymerisations, RAFT, we have tailored different side-chain polymeric structures by controlling monomer composition (MeOAzB/AMPS/MMA) and configuration. We have yielded simultaneous liquid crystalline behaviour and appreciable conductivity in polymers with low concentrations of polar acid groups, by the formation of smectic phases in narrow aggregates. The light-responsiveness of the polymers, via reversible trans-to-cis photoisomerization of azobenzene groups, and the local activation of conductivity at relatively low temperatures, opens the possibility to prepare polymer electrolytes for energy conversion and storage, whose conductivity could be controlled and optimised by external stimuli, including light irradiation.
Detection of 7-Dehydrocholesterol and Vitamin D3 Derivatives in Honey
Authors: Kim Tae-Kang , Atigadda Venkatram , Brzeminski Pawel , Fabisiak Adrian , Tang Edith K. Y. , Tuckey Robert C. , Slominski Andrzej T.
Published: June 2020

20(S)-Hydroxyvitamin D3 (20(OH)D3) is an endogenous metabolite produced by the action of CYP11A1 on the side chain of vitamin D3 (D3). 20(OH)D3 can be further hydroxylated by CYP11A1, CYP27A1, CYP24A1 and/or CYP27B1 to several hydroxyderivatives. CYP11A1 also hydroxylates D3 to 22-monohydroxyvitamin D3 (22(OH)D3), which is detectable in the epidermis. 20-Hydroxy-7-dehydrocholesterol (20(OH)-7DHC) has been detected in the human epidermis and can be phototransformed into 20(OH)D3 following the absorption of ultraviolet B (UVB) energy by the B-ring. 20(OH)D3 and its hydroxyderivatives have anti-inflammatory, pro-differentiation and anti-proliferative effects, comparable to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Since cytochromes P450 with 20- or 25-hydroxylase activity are found in insects participating in ecdysone synthesis from 7-dehydrocholesterol (7DHC), we tested whether D3-hydroxyderivatives are present in honey, implying their production in bees. Honey was collected during summer in the Birmingham area of Alabama or purchased commercially and extracted and analyzed using LC-MS. We detected a clear peak of m/z = 423.324 [M + Na]+ for 20(OH)D3 corresponding to a concentration in honey of 256 ng/g. We also detected peaks of m/z = 383.331 [M + H − H2O]+ for 20(OH)-7DHC and 25(OH)D3 with retention times corresponding to the standards. We further detected species with m/z = 407.329 [M + Na]+ corresponding to the RT of 7DHC, D3 and lumisterol3 (L3). Similarly, peaks with m/z = 399.326 [M + H − H2O]+ were detected at the RT of 1,25(OH)2D3 and 1,20-dihydroxyvitamin D3 (1,20(OH)2D3). Species corresponding to 20-monohydroxylumisterol3 (20(OH)L3), 22-monohydroxyvitamin D3 (22(OH)D3), 20,23-dihydroxyvitamin D3 (20,23(OH)2D3), 20,24/25/26-dihydroxyvitamin D3 (20,24/25/26(OH)2D3) and 1,20,23/24/25/26-trihydroxyvitamin D3 (1,20,23/24/25/26(OH)3D3) were not detectable above the background. In conclusion, the presence of 7DHC and D3 and of species corresponding to 20(OH)-7DHC, 20(OH)D3, 1,20(OH)2D3, 25(OH)D3 and 1,25(OH)2D3 in honey implies their production in bees, although the precise biochemistry and photochemistry of these processes remain to be defined.
Influence of Drainage on Peat Organic Matter: Implications for Development, Stability, and Transformation
Authors: Szajdak Lech W. , Jezierski Adam , Wegner Kazimiera , Meysner Teresa , Szczepański Marek
Published: June 2020

The agricultural use of peatlands, the stabilization of the substrate for building or road construction or for increasing the capacity of soil to support heavy machinery for industrial activities (peat and petroleum extraction), harvesting to provide peat for energy, and the growing media and initiation of chemical processes must be preceded by drainage. As a consequence of drainage, peat underwent an irreversible conversion into moorsh (secondary transformation of the peat). The object of the study was to investigate comparatively the organic matter composition and molecular structure of humic acids (HAs) in the raised bog, fen, and peat-moorsh soils developed in various compositions of botanical cover, peat-forming species, and oxic and anoxic conditions as a result of the oscillation of ground water during drainage as well as to evaluate the vulnerability of soil organic matter (SOM) to decomposition. Drainage was shown to be the principal factor causing the various chemical compositions and physicochemical properties of HAs. Large and significant differences in chemical composition of peat and the properties of HAs were found to be related to the degree of decomposition. The HAs from drained peatlands were less chemically mature. In contrast, the HAs from fen and raised bog were found to be more mature than that of the corresponding drained peatlands. The above findings showed the distinguishable structure of HAs within the soil profile created by the plant residue biodegradation and formed in both oxic and anoxic conditions. The analytical methods of thermal analysis together with the optical densities and paramagnetic behaviour are suitable and effective tools for studying structure–property relationships characterizing the origin and formation process of HAs in various environmental conditions.
Applications of a Standardized Green Tea Catechin Preparation for Viral Warts and Human Papilloma Virus-Related and Unrelated Cancers
Authors: Miyoshi Noriyuki , Tanabe Hiroki , Suzuki Takuji , Saeki Koichi , Hara Yukihiko
Published: June 2020

Most cell-based and animal experiments have shown that green tea catechins (GTC) exhibit various health benefits. In human experimental and epidemiological studies, there are conflicting results, and more precise investigations are required. One of the most effective ways to prove beneficial health effects in humans might be clinical intervention studies. Polyphenon®E was developed as a standardized GTC preparation, which was approved by Food and Drug Administration of US in 2006 as a medication to treat genital warts (Veregen® or sinecatechins). Positive efficacy of Polyphenon®E/sinecatechins/Veregen® (PSV) on anogenital warts has been demonstrated in several epidemiological studies and there have been several case reports to show the clinical effectiveness of PSV. In addition, several studies have provided evidence to suggest that PSV is effective in other human papillomavirus (HPV)-related diseases, although some studies failed to show such effects. Since (−)-epigallocatechin gallate (EGCG) is the major component of PSV, the mechanism of the action of PSV might be deduced from that of EGCG. The microarray analysis of the biopsy samples from the patients suggested that apoptosis induction and the downregulation of inflammation are involved in the mechanism of the action of PSV in the clearance of anogenital warts. Cell-based and animal experiments using PSV also demonstrated effects similar to those elicited by EGCG, explaining how PSV works to induce apoptosis and exert anti-inflammatory actions in HPV-related diseases. Future studies would clarify what kinds of diseases respond effectively to PSV, showing health benefits of GTC and EGCG in humans.
Tannins in Food: Insights into the Molecular Perception of Astringency and Bitter Taste
Authors: Soares Susana , Brandão Elsa , Guerreiro Carlos , Soares Sónia , Mateus Nuno , de Freitas Victor
Published: June 2020

Astringency and bitterness are organoleptic properties widely linked to tannin compounds. Due to their significance to food chemistry, the food industry, and to human nutrition and health, these tannins’ taste properties have been a line of worldwide research. In recent years, significant advances have been made in understanding the molecular perception of astringency pointing to the contribution of different oral key players. Regarding bitterness, several polyphenols have been identified has new agonists of these receptors. This review summarizes the last data about the knowledge of these taste properties perceived by tannins. Ultimately, tannins’ astringency and bitterness are hand-in-hand taste properties, and future studies should be adapted to understand how the proper perception of one taste could affect the perception of the other one.
Mycetoma and Chromoblastomycosis: Perspective for Diagnosis Improvement Using Biomarkers
Authors: Bienvenu Anne-Lise , Picot Stephane
Published: June 2020

Background: Mycetoma and chromoblastomycosis are both chronic subcutaneous infectious diseases that pose an obstacle to socioeconomic development. Besides the therapeutic issue, the diagnosis of most neglected tropical diseases (NTD) is challenging. Confirmation using direct microscopy and culture, recognized as WHO essential diagnostic tests, are limited to specialized facilities. In this context, there is a need for simple user-friendly diagnostic tests to be used in endemic villages. Methods: This review discuss the available biomarkers that could help to improve the diagnostic capacity for mycetoma and chromoblastomycosis in a theoretical and practical perspective. Results: A lack of research in this area has to be deplored, mainly for mycetoma. Biomarkers based on the immune response (pattern of leucocytes, antibody detection), the dermal involvement (extracellular matrix monitoring, protein expression), and the presence of the infectious agent (protein detection) are potential candidates for the detection or follow-up of infection. Conclusion: Confirmatory diagnosis based on specific diagnostic biomarkers will be the basis for the optimal treatment of mycetoma and chromoblastomycosis. It will be part of the global management of NTDs under the umbrella of stewardship activities.
Entropy and Random Walk Trails Water Confinement and Non-Thermal Equilibrium in Photon-Induced Nanocavities
Authors: Gavriil Vassilios , Chatzichristidi Margarita , Christofilos Dimitrios , Kourouklis Gerasimos A. , Kollia Zoe , Bakalis Evangelos , Cefalas Alkiviadis-Constantinos , Sarantopoulou Evangelia
Published: June 2020

Molecules near surfaces are regularly trapped in small cavitations. Molecular confinement, especially water confinement, shows intriguing and unexpected behavior including surface entropy adjustment; nevertheless, observations of entropic variation during molecular confinement are scarce. An experimental assessment of the correlation between surface strain and entropy during molecular confinement in tiny crevices is difficult because strain variances fall in the nanometer scale. In this work, entropic variations during water confinement in 2D nano/micro cavitations were observed. Experimental results and random walk simulations of water molecules inside different size nanocavitations show that the mean escaping time of molecular water from nanocavities largely deviates from the mean collision time of water molecules near surfaces, crafted by 157 nm vacuum ultraviolet laser light on polyacrylamide matrixes. The mean escape time distribution of a few molecules indicates a non-thermal equilibrium state inside the cavity. The time differentiation inside and outside nanocavities reveals an additional state of ordered arrangements between nanocavities and molecular water ensembles of fixed molecular length near the surface. The configured number of microstates correctly counts for the experimental surface entropy deviation during molecular water confinement. The methodology has the potential to identify confined water molecules in nanocavities with life science importance.
Printing of Crumpled CVD Graphene via Blister-Based Laser-Induced Forward Transfer
Authors: Komlenok Maxim S. , Pivovarov Pavel A. , Dezhkina Margarita A. , Rybin Maxim G. , Savin Sergey S. , Obraztsova Elena D. , Konov Vitaly I.
Published: June 2020

The patterning and transfer of a two-dimensional graphene film without damaging its original structure is an urgent and difficult task. For this purpose, we propose the use of the blister-based laser-induced forward transfer (BB-LIFT), which has proven itself in the transfer of such delicate materials. The ease of implementation of laser techniques reduces the number of intermediate manipulations with a graphene film, increasing its safety. The work demonstrates the promise of BB-LIFT of single-layer graphene from a metal surface to a SiO2/Si substrate. The effect of the parameters of this method on the structure of transferred graphene islands is investigated. The relevance of reducing the distance between irradiating and receiving substrates for the transfer of free-lying graphene is demonstrated. The reasons for the damage to the integrity of the carbon film observed in the experiments are discussed. The preservation of the original crystal structure of transferred graphene is confirmed by Raman spectroscopy.
A Double-Blind, Randomized Placebo-Controlled Trial of Probiotic Lactobacillus casei Shirota in Stable Cirrhotic Patients
Authors: Macnaughtan Jane , Figorilli Francesco , García-López Elisabet , Lu Haw , Jones Helen , Sawhney Rohit , Suzuki Kaori , Fairclough Sarah , Marsden Joanne , Moratalla Alba , Cox I. Jane , Thomas Linda , Davies Nathan , Williams Roger , Mookerjee Raj , Wright Gavin , Jalan Rajiv
Published: June 2020

Background: In cirrhosis, a pathological gut microbiome has been linked with immune dysfunction. A pilot study of probiotic Lactobacillus casei Shirota (LcS) in alcoholic cirrhosis demonstrated significant improvement in neutrophil function. This study aimed to evaluate the efficacy of LcS on neutrophil function and significant infection rates in patients with cirrhosis. Methods: 92 cirrhotic patients (Child–Pugh score ≤10) were randomized to receive LcS or placebo, three times daily for six months. Primary end-points were incidence of significant infection and neutrophil function. Secondary end-points were cytokine profile, endotoxin, bacterial DNA positivity, intestinal permeability and quality of life. Results: Rates of infection, decompensation or neutrophil function did not differ between placebo and probiotic groups. LcS significantly reduced plasma monocyte chemotactic protein-1 and, on subgroup analysis, plasma interleukin-1β (alcoholic cirrhosis), interleukin-17a and macrophage inflammatory protein-1β (non-alcoholic cirrhosis), compared with placebo. No significant differences in intestinal permeability, bacterial translocation or metabolomic profile were observed. Conclusion: LcS supplementation in patients with early cirrhosis is safe. Although no significant infections were observed in either group, LcS improved cytokine profile towards an anti-inflammatory phenotype, an effect which appears to be independent of bacterial translocation.
Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers
Authors: Scheinin Mika , Barassi Anna , Junnila Jouni , Lovró Zsófia , Reiner Giorgio , Sarkkinen Essi , MacDonald Anita
Published: June 2020

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic TechnologyTM (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (Cmax) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC0-300 min) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: Cmax for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726, p < 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC0-300min ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism.
The Impact of Diet on Microbiota Evolution and Human Health. Is Diet an Adequate Tool for Microbiota Modulation?
Authors: Moles Laura , Otaegui David
Published: June 2020

The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and the environment. Diet could be assumed to be one of the most prominent factors influencing the microbiota composition. Nevertheless, and in spite of numerous strategies proposed to modulate the human microbiota through dietary means, guidelines to achieve this goal have yet to be established. This review assesses the correlation between social and dietary changes over the course of human evolution and the adaptation of the human microbiota to those changes. In addition, it discusses the main dietary strategies for modulating the microbiota and the difficulties of putting them properly into practice.
Erratum: Yoon, J.J., et al. Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model. Nutrients 2019, 11, 553
Authors: Yoon Jung Joo , Park Ji Hun , Kim Hye Jin , Jin Hong-Guang , Kim Hye Yoom , Ahn You Mee , Kim Youn Chul , Lee Ho Sub , Lee Yun Jung , Kang Dae Gill
Published: June 2020

The authors have requested that the following changes be made to their paper [...]
Study on Cellulose Acetate Butyrate/Plasticizer Systems by Molecular Dynamics Simulation and Experimental Characterization
Authors: Wang Weizhe , Li Lijie , Jin Shaohua , Wang Yalun , Lan Guanchao , Chen Yu
Published: June 2020

Cellulose acetate butyrate (CAB) is a widely used binder in polymer bonded explosives (PBXs). However, the mechanical properties of PBXs bonded with CAB are usually very poor, which makes the charge edges prone to crack. In the current study, seven plasticizers, including bis (2,2-dinitro propyl) formal/acetal (BDNPF/A or A3, which is 1:1 mixture of the two components), azide-terminated glycidyl azide (GAPA), n-butyl-N-(2-nitroxy-ethyl) nitramine (Bu-NENA), ethylene glycol bis(azidoacetate) (EGBAA), diethylene glycol bis(azidoacetate) (DEGBAA), trimethylol nitromethane tris (azidoacetate) (TMNTA) and pentaerythritol tetrakis (azidoacetate) [PETKAA], were studied for the plasticization of CAB. Molecular dynamics simulation was conducted to distinguish the compatibilities between CAB and plasticizers and to predict the mechanical properties of CAB/plasticizer systems. Considering the solubility parameters, binding energies and intermolecular radical distribution functions of these CAB/plasticizer systems comprehensively, we found A3, Bu-NENA, DEGBAA and GAPA are compatible with CAB. The elastic moduli of CAB/plasticizer systems follow the order of CAB/Bu-NENA>CAB/A3>CAB/DEGBAA>CAB/GAPA, and their processing property is in the order of CAB/Bu-NENA>CAB/GAPA>CAB/A3>CAB/DEGBAA. Afterwards, all the systems were characterized by FT-IR, differential scanning calorimetry (DSC), differential thermogravimetric analysis (DTA) and tensile tests. The results suggest A3, GAPA and Bu-NENA are compatible with CAB. The tensile strengths and Young’s moduli of these systems are in the order of CAB/A3>CAB/Bu-NENA>CAB/GAPA, while the strain at break of CAB/Bu-NENA is best, which are consistent with simulation results. Based on these results, it can be concluded that A3, Bu-NENA and GAPA are the most suitable plasticizers for CAB binder in improving mechanical and processing properties. Our work has provided a crucial guidance for the formulation design of PBXs with CAB binder.
Selection of Water-Soluble Chitosan by Microwave-Assisted Degradation and pH-Controlled Precipitation
Authors: Journot Céline M. A. , Nicolle Laura , Lavanchy Yann , Gerber-Lemaire Sandrine
Published: June 2020

In the field of gene therapy, chitosan (CS) gained interest for its promise as a non-viral DNA vector. However, commercial sources of CS lack precise characterization and do not generally reach sufficient solubility in aqueous media for in vitro and in vivo evaluation. As low molecular weight CS showed improved solubility, we investigated the process of CS depolymerization by acidic hydrolysis, using either long time heating at 80 °C or short time microwave-enhanced heating. The resulting depolymerized chitosan (dCS) were analyzed by gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (NMR) to determine their average molecular weight (Mn, Mp and Mw), polydispersity index (PD) and degree of deacetylation (DD). We emphasized the production of water-soluble CS (solubility > 5 mg/mL), obtained in reproducible yield and characteristics, and suitable for downstream functionalization. Optimal microwave-assisted conditions provided dCS with a molecular weight (MW) = 12.6 ± 0.6 kDa, PD = 1.41 ± 0.05 and DD = 85%. While almost never discussed in the literature, we observed the partial post-production aggregation of dCS when exposed to phase changes (from liquid to solid). Repeated cycles of freezing/thawing allowed the selection of dCS fractions which were exempt of crystalline particles formation upon solubilization from frozen samples.
The VLab Framework: An Orchestrator Component to Support Data to Knowledge Transition
Authors: Santoro Mattia , Mazzetti Paolo , Nativi Stefano
Published: June 2020

Over the last decades, to better proceed towards global and local policy goals, there was an increasing demand for the scientific community to support decision-makers with the best available knowledge. Scientific modeling is key to enable the transition from data to knowledge, often requiring to process big datasets through complex physical or empirical (learning-based AI) models. Although cloud technologies provide valuable solutions for addressing several of the Big Earth Data challenges, model sharing is still a complex task. The usual approach of sharing models as services requires maintaining a scalable infrastructure which is often a very high barrier for potential model providers. This paper describes the Virtual Earth Laboratory (VLab), a software framework orchestrating data and model access to implement scientific processes for knowledge generation. The VLab lowers the entry barriers for both developers and users. It adopts mature containerization technologies to access models as source code and to rebuild the required software environment to run them on any supported cloud. This makes VLab fitting in the multi-cloud landscape, which is going to characterize the Big Earth Data analytics domain in the next years. The VLab functionalities are accessible through APIs, enabling developers to create new applications tailored to end-users.
Refining Urban Built-Up Area via Multi-Source Data Fusion for the Analysis of Dongting Lake Eco-Economic Zone Spatiotemporal Expansion
Authors: Li Qianming , Zheng Bohong , Tu Bing , Yang Yusheng , Wang Zhiyuan , Jiang Wei , Yao Kai , Yang Jiawei
Published: June 2020

Rapid urbanization has given rise to serious urban problems. It is crucial to understand the urbanization process to accurately and quickly identify boundary changes in urban built-up areas and implement planning schemes and adjustments in scientific and effective ways. This study proposes a new method to automate and refine the extraction of urban built-up areas by using Landsat and nighttime light (NTL) imagery. The urban agglomeration of Dongting Lake Ecological Economic Zone (UADLEEZ) Landsat data are mapped to NTL data using resampling, superpixel segmentation, and assigning the blank part with the Euclidean distance method. We then compared our findings with those produced via traditional threshold extraction methods. In total, 33 built-up areas of UADLEEZ boundary maps were produced between 1992 and 2018. Thus, we reached the following conclusions: (1) the urban built-up areas obtained via our proposed method are finer than those obtained via other threshold extraction methods; (2) we applied the extraction method to UADLEEZ, and analyzed the expansion of the urban agglomeration based on expansion scale, gravity center offset, and landscape pattern index, the analysis of expansion process is consistent with the actual situation; (3) the proposed method can be used to draw long-term dynamic maps of urban extents in units of years, and the results can be used to update the existing products. This study can serve as a reference for future urban planning, and provide both adjustment programs for relevant departments, and an objective basis for governmental decision-making.
Constrained Linear Deconvolution of GRACE Anomalies to Correct Spatial Leakage
Authors: Seo Ki-Weon , Oh Seokhoon , Eom Jooyoung , Chen Jianli , Wilson Clark R.
Published: June 2020

Time-varying gravity observed by the Gravity Recovery and Climate Experiment (GRACE) satellites measures surface water and ice mass redistribution driven by weather and climate forcing and has emerged as one of the most important data types in measuring changes in Earth’s climate. However, spatial leakage of GRACE signals, especially in coastal areas, has been a recognized limitation in quantitatively assessing mass change. It is evident that larger terrestrial signals in coastal regions spread into the oceans and vice versa and various remedies have been developed to address this problem. An especially successful one has been Forward Modeling but it requires knowledge of geographical locations of mass change to be fully effective. In this study, we develop a new method to suppress leakage effects using a linear least squares operator applied to GRACE spherical harmonic data. The method is effectively a constrained deconvolution of smoothing inherent in GRACE data. It assumes that oceanic mass changes near the coast are negligible compared to terrestrial changes, with additional spatial regularization constraints. Some calibration of constraint weighting is required. We apply the method to estimate surface mass loads over Australia using both synthetic and real GRACE data. Leakage into the oceans is effectively suppressed and when compared with mascon solutions there is better performance over interior basins.