bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Bioturbating Marine Yabby Trypaea australiensis on Sediment Properties in Sandy Sediments Receiving Mangrove Leaf Litter
Authors: Dunn Ryan J. K. , Welsh David T. , Teasdale Peter R. , Gilbert Franck , Poggiale Jean-Christophe , Waltham Nathan J.
Published: November 2019

Laboratory mesocosm incubations were undertaken to investigate the influence of burrowing shrimp Trypaea australiensis (marine yabby) on sediment reworking, physical and chemical sediment characteristics and nutrients in sandy sediments receiving mangrove (Avicennia marina) leaf litter. Mesocosms of sieved, natural T. australiensis inhabited sands, were continually flushed with fresh seawater and pre-incubated for 17 days prior to triplicates being assigned to one of four treatments; sandy sediment (S), sediment + yabbies (S+Y), sediment + leaf litter (organic matter; S+OM) and sediment + yabbies + leaf litter (S+Y+OM) and maintained for 55 days. Mangrove leaf litter was added daily to treatments S+OM and S+Y+OM. Luminophores were added to mesocosms to quantify sediment reworking. Sediment samples were collected after the pre-incubation period from a set of triplicate mesocosms to establish initial conditions prior to the imposition of the treatments and from the treatment mesocosms at the conclusion of the 55-day incubation period. Yabbies demonstrated a clear effect on sediment topography and leaf litter burial through burrow creation and maintenance, creating mounds on the sediment surface ranging in diameter from 3.4 to 12 cm. Within S+Y+OM sediments leaf litter was consistently removed from the surface to sub-surface layers with only 7.5% ± 3.6% of the total mass of leaf detritus added to the mesocosms remaining at the surface at the end of the 55-day incubation period. Yabbies significantly decreased sediment wet-bulk density and increased porosity. Additionally, T. australiensis significantly reduced sediment bio-available ammonium (NH4+bio) concentrations and altered the shape of the concentration depth profile in comparison to the non-bioturbated mesocosms, indicating influences on nutrient cycling and sediment-water fluxes. No significant changes for mean apparent biodiffusion coefficients (Db) and mean biotransport coefficients (r), were found between the bioturbated S+Y and S+Y+OM mesocosms. The findings of this study provide further evidence that T. australiensis is a key-species in shallow intertidal systems playing an important role as an ‘ecosystem engineer’ in soft-bottom habitats by significantly altering physical and chemical structures and biogeochemical function.
A Definite Integral Involving the Logarithmic Function in Terms of the Lerch Function
Authors: Reynolds Robert , Stauffer Allan
Published: November 2019

We present a method using contour integration to evaluate the definite integral of the form ∫ 0 ∞ log k ( a y ) R ( y ) d y in terms of special functions, where R ( y ) = y m 1 + α y n and k , m , a , α and n are arbitrary complex numbers. We use this method for evaluation as well as to derive some interesting related material and check entries in tables of integrals.
ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile
Authors: Favara David M. , Zois Christos E. , Haider Syed , Pires Elisabete , Sheldon Helen , McCullagh James , Banham Alison H. , Harris Adrian L.
Published: November 2019

Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1′s full role and mechanism of function within endothelial biology remains unknown, as do its ligand(s). In this study, ADGRL4/ELTD1 silencing, using two independent small interfering RNAs (siRNAs), was performed in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation, and metabolomics using liquid chromatography-mass spectrometry in order to better characterise ADGRL4/ELTD1′s role in endothelial cell biology. We show that ADGRL4/ELTD1 silencing induced expression of the cytoplasmic metabolic regulator ATP Citrate Lyase (ACLY) and the mitochondria-to-cytoplasm citrate transporter Solute Carrier Family 25 Member 1 (SLC25A1) but had no apparent effect on pathways downstream of ACLY (fatty acid and cholesterol synthesis or acetylation). Silencing induced KIT expression and affected the Notch signalling pathway, upregulating Delta Like Canonical Notch Ligand 4 (DLL4) and suppressing Jagged Canonical Notch Ligand 1 (JAG1) and Hes Family BHLH Transcription Factor 2 (HES2). The effect of ADGRL4/ELTD1 silencing on the cellular metabolic profile was modest but several metabolites were significantly affected. Cis-aconitic acid, uridine diphosphate (UDP)-glucoronate, fructose 2,6-diphosphate, uridine 5-diphosphate, and aspartic acid were all elevated as a result of silencing and phosphocreatine, N-acetylglutamic acid, taurine, deoxyadenosine triphosphate, and cytidine monophosphate were depleted. Metabolic pathway analysis implicated ADGRL4/ELTD1 in pyrimidine, amino acid, and sugar metabolism. In summary, this study shows that ADGRL4/ELTD1 impacts core components of endothelial metabolism and regulates genes involved in endothelial differentiation/homeostasis and Notch signalling.
A Microfluidic Rotational Motor Driven by Circular Vibrations
Authors: Uran Suzana , Bratina Božidar , Šafarič Riko
Published: November 2019

Constructing micro-sized machines always involves the problem of how to bring the energy (electric, magnetic, light, electro wetting, vibrational, etc.) source to the device to produce mechanical movements. The paper presents a rotational micro-sized motor (the diameter of the rotor is 350 µm) driven by low frequency (200–700 Hz) circular vibrations, made by two piezoelectric actuators, through the medium of a water droplet with diameter of 1 mm (volume 3.6 µL). The theoretical model presents how to produce the circular streaming (rotation) of the liquid around an infinitely long pillar with micro-sized diameter. The practical application has been focused to make a time-stable circular stream of the medium around the finite long vibrated pillar with diameter of 80 µm in the presence of disturbances produced by the vibrated plate where the pillar is placed. Only the time-stable circular stream in the water droplet around the pillar produces enough energy to rotate the micro-sized rotor. The rotational speed of the rotor is controlled in both directions from −20 rad/s to +26 rad/s. 3D printed mechanical amplifiers of vibrations, driven by piezoelectric actuators, amplify the amplitude of the piezoelectric actuator up to 20 µm in the frequency region of 200 to 700 Hz.
A Micropatterning Strategy to Study Nuclear Mechanotransduction in Cells
Authors: Bautista Markville , Fernandez Anthony , Pinaud Fabien
Published: November 2019

Micropatterning techniques have been widely used in biology, particularly in studies involving cell adhesion and proliferation on different substrates. Cell micropatterning approaches are also increasingly employed as in vitro tools to investigate intracellular mechanotransduction processes. In this report, we examined how modulating cellular shapes on two-dimensional rectangular fibronectin micropatterns of different widths influences nuclear mechanotransduction mediated by emerin, a nuclear envelope protein implicated in Emery–Dreifuss muscular dystrophy (EDMD). Fibronectin microcontact printing was tested onto glass coverslips functionalized with three different silane reagents (hexamethyldisilazane (HMDS), (3-Aminopropyl)triethoxysilane (APTES) and (3-Glycidyloxypropyl)trimethoxysilane (GPTMS)) using a vapor-phase deposition method. We observed that HMDS provides the most reliable printing surface for cell micropatterning, notably because it forms a hydrophobic organosilane monolayer that favors the retainment of surface antifouling agents on the coverslips. We showed that, under specific mechanical cues, emerin-null human skin fibroblasts display a significantly more deformed nucleus than skin fibroblasts expressing wild type emerin, indicating that emerin plays a crucial role in nuclear adaptability to mechanical stresses. We further showed that proper nuclear responses to forces involve a significant relocation of emerin from the inner nuclear envelope towards the outer nuclear envelope and the endoplasmic reticulum membrane network. Cell micropatterning by fibronectin microcontact printing directly on HMDS-treated glass represents a simple approach to apply steady-state biophysical cues to cells and study their specific mechanobiology responses in vitro.
Rhizosphere Metagenomics of Paspalum scrobiculatum L. (Kodo Millet) Reveals Rhizobiome Multifunctionalities
Authors: Prabha Ratna , Singh Dhananjaya P. , Gupta Shailendra , Gupta Vijai Kumar , El-Enshasy Hesham A. , Verma Mukesh K.
Published: November 2019

Multifunctionalities linked with the microbial communities associated with the millet crop rhizosphere has remained unexplored. In this study, we are analyzing microbial communities inhabiting rhizosphere of kodo millet and their associated functions and its impact over plant growth and survival. Metagenomics of Paspalum scrobiculatum L.(kodo millet) rhizopshere revealed taxonomic communities with functional capabilities linked to support growth and development of the plants under nutrient-deprived, semi-arid and dry biotic conditions. Among 65 taxonomically diverse phyla identified in the rhizobiome, Actinobacteria were the most abundant followed by the Proteobacteria. Functions identified for different genes/proteins led to revelations that multifunctional rhizobiome performs several metabolic functions including carbon fixation, nitrogen, phosphorus, sulfur, iron and aromatic compound metabolism, stress response, secondary metabolite synthesis and virulence, disease, and defense. Abundance of genes linked with N, P, S, Fe and aromatic compound metabolism and phytohormone synthesis—along with other prominent functions—clearly justifies growth, development, and survival of the plants under nutrient deprived dry environment conditions. The dominance of actinobacteria, the known antibiotic producing communities shows that the kodo rhizobiome possesses metabolic capabilities to defend themselves against biotic stresses. The study opens avenues to revisit multi-functionalities of the crop rhizosphere for establishing link between taxonomic abundance and targeted functions that help plant growth and development in stressed and nutrient deprived soil conditions. It further helps in understanding the role of rhizosphere microbiome in adaptation and survival of plants in harsh abiotic conditions.
Elevation is Associated with Human Skin Microbiomes
Authors: Li Huan , Wang Yijie , Yu Qiaoling , Feng Tianshu , Zhou Rui , Shao Liye , Qu Jiapeng , Li Nan , Bo Tingbei , Zhou Huakun
Published: November 2019

Human skin microbiota plays a crucial role in the defense against pathogens, and is associated with various skin diseases. High elevation is positively correlated with various extreme environmental conditions (i.e., high ultraviolet radiation), which may exert selection pressure on skin microbiota, and therefore influence human health. Most studies regarding skin microbial communities have focused on low-elevation hosts. Few studies have explored skin microbiota in high-elevation humans. Here, we investigated the diversity, function, assembly, and co-occurrence patterns of skin microbiotas from 35 health human subjects across three body sites (forehead, opisthenar, and palm) and seven elevation gradients from 501 to 3431 m. Alpha diversity values (i.e., Shannon diversity and observed operational taxonomic units (OTUs)) decreased with increasing elevation regardless of the body site, while beta diversity (Jaccard and Bray–Curtis dissimilarities) showed an increasing trend with elevation. Elevation is a significant factor that influences human skin microbiota, even after controlling host-related factors. Skin microbiotas at high elevation with more than 3000 m on the Qinghai–Tibet Plateau, had a significant structural or functional separation from those at low elevation with less than 3000 m. Notably, the clustering coefficient, average degree, and network density were all lower at high-elevation than those at low-elevation, suggesting that high-elevation skin networks were more fragile and less connected. Phylogenetic analysis showed that human skin microbiotas are mainly dominated by stochastic processes (58.4%–74.6%), but skin microbiotas at high-elevation harbor a greater portion of deterministic processes than those at low-elevation, indicating that high-elevation may be conducive to the promotion of deterministic processes. Our results reveal that the filtering and selection of the changeable high-elevation environment on the Qinghai–Tibet Plateau may lead to less stable skin microbial community structures.
Probiotic Effects of a Novel Strain, Acinetobacter KU011TH, on the Growth Performance, Immune Responses, and Resistance against Aeromonas hydrophila of Bighead Catfish (Clarias macrocephalus Günther, 1864)
Authors: Bunnoy Anurak , Na-Nakorn Uthairat , Srisapoome Prapansak
Published: November 2019

In the present study, the novel probiotic strain Acinetobacter KU011TH with an evident lack of pathogenicity in catfish was experimented. Three practical administration routes, namely, feed additive (FD), water-soluble additive (SOL), and a combination route (FD+SOL), were applied in two sizes of catfish. After 120 days of FD+SOL administration, catfish fingerlings (15 g) exhibited a significant improvement in all tested growth performance parameters. For 15- and 30-day applications at the juvenile stage (150 g), phagocytic activity, phagocytic index, lysozyme activity, respiratory burst activity, alternative complement pathway, and bactericidal activity were significantly increased. Furthermore, probiotic-administered bighead catfish exhibited an upregulated expression of several immune-related genes in tested organs. Significant colonization by Acinetobacter KU011TH in rearing water and on skin and gills was observed among experimental groups. Histological analysis clearly indicated enhanced physical characteristics of skin mucosal immunity in the treated groups. No histopathological changes in the gills, skin, intestine or liver were observed among the fish groups. Interestingly, after challenge with Aeromonas hydrophila, the survival rates of the treated groups were significantly higher than those of the controls. In conclusion, the novel probiont Acinetobacter KU011TH provides a potent strategy for improvement in growth and disease resistance, which is an important steppingstone for sustaining catfish aquaculture.
Trace Elements in Magnetite from the Pagoni Rachi Porphyry Prospect, NE Greece: Implications for Ore Genesis and Exploration
Authors: Mavrogonatos Constantinos , Voudouris Panagiotis , Berndt Jasper , Klemme Stephan , Zaccarini Federica , Spry Paul G. , Melfos Vasilios , Tarantola Αlexandre , Keith Manuel , Klemd Reiner , Haase Karsten
Published: November 2019

Magnetite is a common accessory phase in various types of ore deposits. Its trace element content has proven to have critical implications regarding petrogenesis and as guides in the exploration for ore deposits in general. In this study we use LA-ICP-MS (laser ablation-inductively coupled plasma-mass spectrometry) analyses of trace elements to chemically characterize magnetite from the Pagoni Rachi Cu–Mo–Re–Au porphyry-style prospect, Thrace, northern Greece. Igneous magnetite mostly occurs as euhedral grains, which are commonly replaced by hematite in fresh to propylitic-altered granodiorite porphyry, whereas, hydrothermal magnetite forms narrow veinlets or is disseminated in sodic/potassic-calcic altered (albite + K-feldspar + actinolite + biotite + chlorite) granodiorite porphyry. Magnetite is commonly associated with chalcopyrite and pyrite and locally exhibits martitization. Laser ablation ICP-MS analyses of hydrothermal magnetite yielded elevated concentrations in several trace elements (e.g., V, Pb, W, Mo, Ta, Zn, Cu, and Nb) whereas Ti, Cr, Ni, and Sn display higher concentration in its magmatic counterpart. A noteworthy enrichment in Mo, Pb, and Zn is an unusual feature of hydrothermal magnetite from Pagoni Rachi. High Si, Al, and Ca values in a few analyses of hydrothermal magnetite imply the presence of submicroscopic or nano-inclusions (e.g., chlorite, and titanite). The trace element patterns of the hydrothermal magnetite and especially the decrease in its Ti content reflect an evolution from the magmatic towards the hydrothermal conditions under decreasing temperatures, which is consistent with findings from analogous porphyry-style deposits elsewhere.
Four New Iridoid Metabolites Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells
Authors: Chang Fang-Pin , Huang Shyh-Shyun , Lee Tzong-Huei , Chang Chi-I , Kuo Tzong-Fu , Huang Guan-Jhong , Kuo Yueh-Hsiung
Published: November 2019

One new iridoid, namely neonanin C (1) one monocyclic iridoid ring-opened derivative namely neonanin D (2), two new bis-iridoid derivatives namely reticunin A (3) and reticunin B (4) with sixteen known compounds (5–20) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1–20 were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cell line. The results showed that all compounds exhibited no obvious cytotoxicity compared to the control group and five compounds including isoboonein (7), syringaresinol (10), (+)-medioresinol (12), protocatechuic acid (14) and trans-caffeic acid (15) exhibited inhibitory activities with IC50 values at 86.27 ± 3.45; 9.18 ± 1.90; 76.18 ± 2.42; 72.91 ± 4.97 and 95.16 ± 1.20 µg/mL, respectively.
Lignocellulosic Biomass Fractionation by Mineral Acids and Resulting Extract Purification Processes: Conditions, Yields, and Purities
Authors: Oriez Vincent , Peydecastaing Jérôme , Pontalier Pierre-Yves
Published: November 2019

Fractionation of lignocellulose is a fundamental step in the valorization of cellulose, hemicelluloses, and lignin to produce various sustainable fuels and chemicals. Mineral acid fractionation is one of the most applied process and leads to the solubilization and hydrolysis of cellulose and hemicelluloses, whereas most of the lignin remains insoluble and can be separated from the extract. The obtained monomeric sugars in the acid extract are in solution with salts, sugar degradation products, and phenolic molecules. Downstream processing is required to purify the sugars and further valorize them into fuels or chemicals with the use of chemical or biochemical reactions. This purification step also allows the recycling of the mineral acid and the valorization of the sugar degradation products and the co-extracted phenolic molecules, adding value to the whole biorefinery scheme. Many purification techniques have been studied, providing several options in terms of yields, purities, and cost of the process. This review presents the conditions used for the mineral acid fractionation step and a wide variety of purification techniques applied on the obtained hydrolysate, with a focus on the associated yields and purities. Values from the literature are expressed in a standard way in order to simplify comparison between the different processes.
Applications of Tea (Camellia sinensis) and Its Active Constituents in Cosmetics
Authors: Koch Wojciech , Zagórska Justyna , Marzec Zbigniew , Kukula-Koch Wirginia
Published: November 2019

Studies on the cosmetic applications of plant extracts are increasingly appearing in the scientific literature, which is due to the growing popularity of skincare products around the world. In the light of the observed changes, a return to natural treatment and skincare with cosmetics free of harmful substances or toxic preservatives is visible. Currently, tea extracts, due to their rich composition and various biological actions, play an important role among the dietary supplements and cosmetics. This review is intended to collect the reports on the properties of the tea plant, its extracts and preparations in cosmetology: for skin care products and for the treatment of selected dermatological diseases. Particular attention is paid to its antioxidant, anti-hyaluronidase, anti-inflammatory, slimming, hair-strengthening, photoprotective and sealing blood vessels properties.
Antimicrobial Activity and Chemical Constitution of the Crude, Phenolic-Rich Extracts of Hibiscus sabdariffa, Brassica oleracea and Beta vulgaris
Authors: Abdel-Shafi Seham , Al-Mohammadi Abdul-Raouf , Sitohy Mahmoud , Mosa Basma , Ismaiel Ahmed , Enan Gamal , Osman Ali
Published: November 2019

Crude, phenolic-rich extracts (CPREs) were isolated from different sources, such as Hibiscus sabdariffa (H. sabdariffa), Brassica oleracea var. capitata f. rubra (B. oleracea) and Beta vulgaris (B. vulgaris) and characterized. These CPREs showed potential antibacterial and antifungal activities. H. sabdariffa CPRE (HCPRE) is the most potent, as it inhibited all tested bacteria and fungi. Total anthocyanins content (TAC), total phenolic content (TPC) and total flavonoid content (TFC) were estimated in all three CPREs. H. sabdariffa contained 4.2 mg/100 g TAC, 2000 mg/100 g of TPC and 430 mg/100 g of TFC in a dry weight sample. GC–MS analysis of HCPRE showed 10 different active compounds that have antimicrobial effects against pathogenic bacteria and fungi, especially alcoholic compounds, triazine derivatives and esters. Scanning and transmission electron microscopy images of Staphylococcus aureus DSM 1104 and Klebsiella pneumonia ATCC 43816 treated with HCPRE (50 μg/mL) exhibited signs of asymmetric, wrinkled exterior surfaces, cell deformations and loss of cell shapes; and adherence of lysed cell content led to cell clumping, malformations, blisters, cell depressions and diminished cell numbers. This indicates death of bacterial cells and loss of cell contents. Aspergillus ochraceus EMCC516 (A. ochraceus, when treated with 100 μg/mL of HCPRE showed irregular cell organelles and cell vacuolation.
NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide
Authors: Castiglia Francesca , Zevolini Fabrizia , Riolo Giulia , Brunetti Jlenia , De Lazzari Alessandra , Moretto Alberto , Manetto Giulia , Fragai Marco , Algotsson Jenny , Evenäs Johan , Bracci Luisa , Pini Alessandro , Falciani Chiara
Published: November 2019

The synthetic antimicrobial peptide SET-M33 is being developed as a possible new antibacterial candidate for the treatment of multi-drug resistant bacteria. SET-M33 is a branched peptide featuring higher resistance and bioavailability than its linear analogues. SET-M33 shows antimicrobial activity against different species of multi-resistant Gram-negative bacteria, including clinically isolated strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanii and Escherichia coli. The secondary structure of this 40 amino acid peptide was investigated by NMR to fully characterize the product in the framework of preclinical studies. The possible presence of helixes or β-sheets in the structure had to be explored to predict the behavior of the branched peptide in solution, with a view to designing a formulation for parenteral administration. Since the final formulation of SET-M33 will be strictly defined in terms of counter-ions and additives, we also report the studies on a new salt form, SET-M33 chloride, that retains its activity against Gram-negative bacteria and gains in solubility, with a possible improvement in the pharmacokinetic profile. The opportunity of using a chloride counter-ion is very convenient from a process development point of view and did not increase the toxicity of the antimicrobial drug.
Effect of Intermittent Microwave Volumetric Heating on Dehydration, Energy Consumption, Antioxidant Substances, and Sensory Qualities of Litchi Fruit during Vacuum Drying
Authors: Cao Xiaohuang , Chen Jianping , Islam Md. Nahidul , Xu Wanxiu , Zhong Saiyi
Published: November 2019

To examine the processing characteristics and high quality of an improved microwave vacuum drying system, litchi fruits were dried using intermittent microwave volumetric heating while microwave vacuum drying at 2 W/g was carried out for comparison; the intermittent microwave heating profiles were set as (1) 5 min drying-on, 5 min drying-off; (2) 5 min drying-on, 10 min drying-off; and (3) 5 min drying-on, 15 min drying-off. Energy consumption during drying was determined, and physicochemical properties such as moisture content, vitamin C, total phenolics, color, and sensory evaluation of dried products were assessed. In microwave vacuum drying, intermittent microwave volumetric heating was found to be energy-efficient (about 32 KJ/g to 45 KJ/g) and saved at least 31% of energy consumption compared with microwave vacuum drying as well as decreasing product browning. In addition, microwave volumetric heating had no substantial effects on sugar and protein contents, while antioxidants were affected significantly (p ≤ 0.05). Moreover, sensory evaluation showed that intermittent microwave-assisted vacuum drying (IMVD) increased the acceptance of the dried product compared with microwave vacuum drying (MVD).
Validation of an HPLC Method for the Simultaneous Quantification of Metabolic Reaction Products Catalysed by CYP2C11 Enzymes in Rat Liver Microsomes: In Vitro Inhibitory Effect of Salicylic Acid on CYP2C11 Enzyme
Authors: Salhab Hassan , Naughton Declan P. , Barker James
Published: November 2019

The inhibitory effect of new chemical entities on rat liver P450 marker activities was investigated in a functional approach towards drug development. Treatment of colorectal cancer (CRC) and chemoprevention using salicylic acid has gained a lot of attention, mainly in the prevention of the onset of colon cancer. Thus, an in vitro inhibitory effect of salicylic acid on rat CYP2C11 activity was examined by using high performance liquid chromatography (HPLC). High performance liquid chromatography analysis of a CYP2C11 assay was developed on a reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) at 243 nm using 32% phosphate buffer (pH 3.36) and 68% methanol as a mobile phase. The CYP2C11 assay showed good linearity for all components (R2 > 0.999). Substrates and metabolites were found to be stable for up to 72 h. Additionally, the method demonstrated good reproducibility, intra- and inter-day precision (<15%), acceptable recovery and accuracy (80%–120%), and low detection (1.3501 µM and 3.2757 µM) and quantitation limit values (4.914 µM and 9.927 µM) for 16α-hydroxytestosterone and testosterone, respectively. Salicylic acid acts reversibly as a noncompetitive (weak) inhibitor with Ki = 84.582 ± 2.67 µM (concentration of inhibitor to cause 50% inhibition of original enzyme activity (IC50) = 82.70 ± 2.67 µM) for CYP2C11 enzyme activity. This indicates a low potential to cause toxicity and drug–drug interactions.
Anti-Amyloidogenic Effects of Asarone Derivatives From Perilla frutescens Leaves Against Beta-Amyloid Aggregation and Nitric Oxide Production
Authors: Lee Jae Eun , Kim Nayeon , Yeo Ji Yun , Seo Dae-Gun , Kim Sunggun , Lee Jae-Sun , Hwang Kwang Woo , Park So-Young
Published: November 2019

Alzheimer’s disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aβ) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aβ aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of Perilla frutescens (L.) Britton (Lamiaceae) and its hexane fraction on Aβ aggregation. Here, the hexane fraction of P. frutescens was subjected to diverse column chromatography based on activity-guided isolation methodology. This approach identified five asarone derivatives including 2,3-dimethoxy-5-(1E)-1-propen-1-yl-phenol (1), β-asarone (2), 3-(2,4,5-trimethoxyphenyl)-(2E)-2-propen-1-ol (3), asaronealdehyde (4), and α-asarone (5). All five asarone derivatives efficiently reduced the aggregation of Aβ and disaggregated preformed Aβ aggregates in a dose-dependent manner as determined by a Thioflavin T (ThT) fluorescence assay. Furthermore, asarone derivatives protected PC12 cells from Aβ aggregate-induced toxicity by reducing the aggregation of Aβ, and significantly reduced NO production from LPS-stimulated BV2 microglial cells. Taken together, these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in AD.
Synthesis and Evaluation of Novel 2H-Benzo[e]-[1,2,4]thiadiazine 1,1-Dioxide Derivatives as PI3Kδ Inhibitors
Authors: Gong Ya-Ping , Tang Long-Qian , Liu Tong-Shen , Liu Zhao-Peng
Published: November 2019

In previous work, we applied the rotation-limiting strategy and introduced a substituent at the 3-position of the pyrazolo [3,4-d]pyrimidin-4-amine as the affinity element to interact with the deeper hydrophobic pocket, discovered a series of novel quinazolinones as potent PI3Kδ inhibitors. Among them, the indole derivative 3 is one of the most selective PI3Kδ inhibitors and the 3,4-dimethoxyphenyl derivative 4 is a potent and selective dual PI3Kδ/γ inhibitor. In this study, we replaced the carbonyl group in the quinazolinone core with a sulfonyl group, designed a series of novel 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives as PI3Kδ inhibitors. After the reduction of nitro group in N-(2,6-dimethylphenyl)-2-nitrobenzenesulfonamide 5 and N-(2,6-dimethylphenyl)-2-nitro-5-fluorobenzenesulfonamide 6, the resulting 2-aminobenzenesulfonamides were reacted with trimethyl orthoacetate to give the 3-methyl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives. After bromination of the 3-methyl group, the nucleophilic substitution with the 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine provided the respective iodide derivatives, which were further reacted with a series of arylboronic acids via Suzuki coupling to furnish the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives 15a–J and 16a–d. In agreement with the quinazolinone derivatives, the introduction of a 5-indolyl or 3,4-dimethoxyphenyl at the affinity pocket generated the most potent analogues 15a and 15b with the IC50 values of 217 to 266 nM, respectively. In comparison with the quinazolinone lead compounds 3 and 4, these 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives exhibited much decreased PI3Kδ inhibitory potency, but maintained the high selectivity over other PI3K isoforms. Unlike the quinazolinone lead compound 4 that was a dual PI3Kδ/γ inhibitor, the benzthiadiazine 1,1-dioxide 15b with the same 3,4-dimethoxyphenyl moiety was more than 21-fold selective over PI3Kγ. Moreover, the introducing of a fluorine atom at the 7-position of the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide core, in general, was not favored for the PI3Kδ inhibitory activity. In agreement with their high PI3Kδ selectivity, 15a and 15b significantly inhibited the SU-DHL-6 cell proliferation.
The Property Characterization of α-Sialon/Ni Composites Synthesized by Spark Plasma Sintering
Authors: Adeniyi Adedayo Sheriff , Ahmed Bilal Anjum , Hakeem Abbas Saeed , Patel Faheemuddin , Bakare Akolade Idris , Ul-Hamid Anwar , Khan Amir Azam , Ehsan Muhammad Ali , Khan Tahir Irfan
Published: November 2019

This study investigates the effect of micron-sized nickel particle additions on the microstructural, thermal, and mechanical property changes of α-sialon ceramic composites. The α-sialon/Ni composites were synthesized with an increasing amount of Ni (10–40 wt.%) using the spark plasma sintering technique and nanosized alpha precursors at a relatively low synthesis temperature of 1500 °C with a holding time of 30 min in each case. The density of the samples increased with the increase in Ni content of up to 15 wt.% and, with the further increase in Ni content, it became almost constant with a slight decrease. Furthermore, thermal conductivity and thermal expansion properties of Ni-sialon composites improved slightly with the inclusion of 10 wt.% Ni. The addition of Ni to α-sialon matrix resulted in a decrease in the hardness of the composites from HV10 21.6 to HV10 16.3, however the presence of Ni as a softer interfacial phase resulted in a substantial increase in the fracture toughness of these composites. Fracture toughness was found to increase by approximately 91% at 40 wt.% Ni addition.
Revealing the Importance of Aging, Environment, Size and Stabilization Mechanisms on the Stability of Metal Nanoparticles: A Case Study for Silver Nanoparticles in a Minimally Defined and Complex Undefined Bacterial Growth Medium
Authors: De Leersnyder Ilse , De Gelder Leen , Van Driessche Isabel , Vermeir Pieter
Published: November 2019

Although the production and stabilization of metal nanoparticles (MNPs) is well understood, the behavior of these MNPs (possible aggregation or disaggregation) when they are intentionally or unintentionally exposed to different environments is a factor that continues to be underrated or overlooked. A case study is performed to analyze the stability of silver nanoparticles (AgNPs)—one of the most frequently used MNPs with excellent antibacterial properties—within two bacterial growth media: a minimally defined medium (IDL) and an undefined complex medium (LB). Moreover, the effect of aging, size and stabilization mechanisms is considered. Results clearly indicate a strong aggregation when AgNPs are dispersed in IDL. Regarding LB, the 100 nm electrosterically stabilized AgNPs remain stable while all others aggregate. Moreover, a serious aging effect is observed for the 10 nm electrostatically stabilized AgNPs when added to LB: after aggregation a restabilization effect occurs over time. Generally, this study demonstrates that the aging, medium composition (environment), size and stabilization mechanism—rarely acknowledged as important factors in nanotoxicity studies—have a profound impact on the AgNPs stabilization and should gain more attention in scientific research.
Fragmented Dosing of β-alanine Induces A Body Weight-Independent Pharmacokinetic Response
Authors: Stautemas Jan , Van de Loock Alexia , Van der Stede Thibaux , Pringels Lauren , Derave Wim
Published: November 2019

Personalised dosing of performance-enhancing food supplements is a hot topic. β-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48–139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = −0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.
The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function
Authors: Aboufarrag Hassan T. , Needs Paul W. , Rimbach Gerald , Kroon Paul A.
Published: November 2019

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.
Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review
Authors: Fernández-Palanca Paula , Fondevila Flavia , Méndez-Blanco Carolina , Tuñón María J. , González-Gallego Javier , Mauriz José L.
Published: November 2019

Quercetin is a flavonoid present in fruits, vegetables and plants with antioxidant, anti-inflammatory and anticancer properties. Its beneficial activities have been demonstrated in different human pathologies, including hepatoprotective effects against liver disorders. High mortality and late diagnosis of the primary liver tumor hepatocarcinoma (HCC) makes this cancer an interesting target for the study of quercetin effects. Our aim was to systematically review antitumor activities of quercetin in HCC preclinical studies employing single, encapsulated, combined or derived quercetin forms. Literature search was conducted in PubMed, Scopus and Web of Science (WOS), and 39 studies were finally included. We found that 17 articles evaluated quercetin effects alone, six used encapsulated strategy, 10 combined this flavonoid, two decided to co-encapsulate it and only four studied effects of quercetin derivatives, highlighting that only nine included in vivo models. Results evidence the quercetin antiproliferative and proapoptotic properties against HCC either alone and with the mentioned strategies; nevertheless, few investigations assessed specific activities on different processes related with cancer progression. Overall, further studies including animal models are needed to deeper investigate the precise mechanisms of action of quercetin as antitumor agent, as well as the potential of novel strategies aimed to improve quercetin effects in HCC.
An Anthocyanin-Rich Mixed-Berry Intervention May Improve Insulin Sensitivity in a Randomized Trial of Overweight and Obese Adults
Authors: Solverson Patrick M. , Henderson Theresa R. , Debelo Hawi , Ferruzzi Mario G. , Baer David J. , Novotny Janet A.
Published: November 2019

Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15 ± 0.066 ln pmol min/mL, mean ± SE, p = 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17 ± 0.093 ln mg·min/dL, mean ± SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.
Determination of Stable Co-Amorphous Drug–Drug Ratios from the Eutectic Behavior of Crystalline Physical Mixtures
Authors: Kissi Eric Ofosu , Khorami Keyoomars , Rades Thomas
Published: November 2019

Co-amorphous drug–drug systems have been developed with the overall aim of improving the physical stability of two or more amorphous drugs. Co-amorphous systems often show good physical stability, and higher solubility and dissolution rates compared to their crystalline counterparts. The aim of this study is to determine if eutectic mixtures of two drugs can form stable co-amorphous systems. Three drug–drug mixtures, indomethacin–naproxen (IND−NAP), nifedipine–paracetamol (NIF−PAR), and paracetamol–celecoxib (PAR−CCX), were investigated for their eutectic and co-amorphization behavior as well as their physical stability in the co-amorphous form. The phase diagrams of the crystalline mixtures and the thermal behavior of the co-amorphous systems were analyzed by differential scanning calorimetry. The solid-state form and physical stability of the co-amorphous systems were analyzed using X-ray powder diffractometry during storage at room temperature at dry conditions. Initial eutectic screening using nifedipine (NIF), paracetamol (PAR), and celecoxib (CCX) indicated that IND−NAP, NIF−PAR, and PAR−CCX can form eutectic mixtures. Phase diagrams were then constructed using theoretical and experimental values. These systems, at different drug-to-drug ratios, were melted and cooled to form binary mixtures. Most mixtures were found to be co-amorphous systems, as they were amorphous and exhibited a single glass transition temperature. The stability study of the co-amorphous systems indicated differences in their physical stability. Comparing the phase diagrams with the physical stability of the co-amorphous mixtures, it was evident that the respective drug–drug ratio that forms the eutectic point also forms the most stable co-amorphous system. The eutectic behavior of drug–drug systems can thus be used to predict drug ratios that form the most stable co-amorphous systems.
Implementation of a Health-System Wide Antimicrobial Stewardship Program in Omaha, NE
Authors: Anthone Jennifer , Boldt Dayla , Alexander Bryan , Carroll Cassara , Ased Sumaya , Schmidt David , Vivekanandan Renuga , Destache Christopher J.
Published: November 2019

The Centers for Medicare and Medicaid Services (CMS) have mandated that acute care and critical access hospitals implement an Antimicrobial Stewardship (AMS) Program. This manuscript describes the process that was implemented to ensure CMS compliance for AMS, across a 14-member health system (eight community hospitals, five critical access hospitals, and an academic medical center) in the Omaha metro area, and surrounding cities. The addition of the AMS program to the 14-member health system increased personnel, with a 0.5 full-time equivalent (FTE) infectious diseases (ID) physician, and 2.5 FTE infectious diseases trained clinical pharmacists to support daily AMS activities. Clinical decision support software had previously been implemented across the health system, which was also key to the success of the program. Overall, in its first year, the AMS program demonstrated a $1.2 million normalized reduction (21% total reduction in antimicrobial purchases) in antimicrobial expenses. The ability to review charts daily for antimicrobial optimization with ID pharmacist and physician support, identify facility specific needs and opportunities, and to collect available data endpoints to determine program effectiveness helped to ensure the success of the program.
Super Effective Removal of Toxic Metals Water Pollutants Using Multi Functionalized Polyacrylonitrile and Arabic Gum Grafts
Authors: Elbedwehy Ahmed M. , Abou-Elanwar Ali M. , Ezzat Abdelrahman O. , Atta Ayman M.
Published: November 2019

Super adsorbent polymers can be considered to be a very efficient solution for wastewater treatment. In general, their adsorption capacities depend on the type and amount of the functional groups present on the surface of the polymers, while their economic value is affected by their cost. Therefore, this study aims to understand the effect of multi-functionalization of cheap Arabic gum on the adsorption capability toward heavy metals. Graft copolymers of polyacrylonitrile (PAN) onto Arabic gum (AG) were prepared in aqueous solution using (KMnO4/HNO3) as a redox initiator. Chemical modification of the graft copolymer was carried out by reaction with hydrazine hydrochloride followed by hydrolysis in the basic medium. The modified graft product was characterized by various techniques, such as Fourier transform infrared spectroscopy (FTIR), elemental analysis, scanning electron microscope (SEM), and X-ray powder diffraction (XRD). The modified graft copolymer was used to adsorb Pb2+, Cd2+ and Cu2+ from their aqueous solutions using batch extraction. Different parameters influence the uptake behavior, including contact time, pH, and the initial concentration of the metal ions; all of these were investigated. The kinetics were investigated using the pseudo first order and pseudo second order, and the equilibrium data were analyzed using the Langmuir and Freundlich model. The modified graft product showed the superadsorbent capacity to obtain maximum values (Qmax) 1017, 413 and 396 mg/g for Pb2+, Cd2+ and Cu2+, respectively. Acid treatment with 0.2 M HNO3 resulted in 96%, 99% and 99% metal recovery for the Pb2+, Cd2+ and Cu2+, respectively. This indicates the recyclability of product for further usage upon drying between treatments.
Thermoresponsive Poly(ß-hydroxyl amine)s: Synthesis of a New Stimuli Responsive Amphiphilic Homopolymer Family through Amine-Epoxy ‘Click’ Polymerization
Authors: Hong Jeonghui , Khan Anzar
Published: November 2019

A new synthesis of amphiphilic homopolymers is described. In this synthesis, commercially available and inexpensive primary amines and di-epoxide molecules are utilized as AA- and BB-types of monomers in an amine-epoxy ‘click’ polymerization process. This process can be carried out in water and at room temperature. It does not require a catalyst or inert conditions and forms no byproducts. Therefore, the polymer synthesis can be carried out in open-air and bench-top conditions and a post-synthesis purification step is not required. The modularity of the synthesis, on the other hand, allows for facile structural modulation and tuning of the thermally triggered aggregation process in the temperature range of 7 to 91 °C. Finally, the underlying principles can be translated from linear architectures to polymer networks (hydrogels).