bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance
Authors: Marrs Emma C.L. , Varadi Linda , Bedernjak Alexandre F. , Day Kathryn M. , Gray Mark , Jones Amanda L. , Cummings Stephen P. , Anderson Rosaleen J. , Perry John D.
Published: April 2020

Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess their efficacy in the context of widespread resistance to conventional agents. In the 1970s, much work was performed on the development of peptide mimetics, exemplified by the phosphonopeptide, alafosfalin. We investigated the activity of alafosfalin, di-alanyl fosfalin and β-chloro-L-alanyl-β-chloro-L-alanine against 297 bacterial isolates, including carbapenemase-producing Enterobacterales (CPE) (n = 128), methicillin-resistant Staphylococcus aureus (MRSA) (n = 37) and glycopeptide-resistant enterococci (GRE) (n = 43). The interaction of alafosfalin with meropenem was also examined against 20 isolates of CPE. The MIC50 and MIC90 of alafosfalin for CPE were 1 mg/L and 4 mg/L, respectively and alafosfalin acted synergistically when combined with meropenem against 16 of 20 isolates of CPE. Di-alanyl fosfalin showed potent activity against glycopeptide-resistant isolates of Enterococcus faecalis (MIC90; 0.5 mg/L) and Enterococcus faecium (MIC90; 2 mg/L). Alafosfalin was only moderately active against MRSA (MIC90; 8 mg/L), whereas β-chloro-L-alanyl-β-chloro-L-alanine was slightly more active (MIC90; 4 mg/L). This study shows that phosphonopeptides, including alafosfalin, may have a therapeutic role to play in an era of increasing antibacterial resistance.
Characterization, Quantification and Quality Assessment of Avocado (Persea americana Mill.) Oils
Authors: Wang Mei , Yu Ping , Chittiboyina Amar G. , Chen Dilu , Zhao Jianping , Avula Bharathi , Wang Yan-Hong , Khan Ikhlas A.
Published: April 2020

Avocado oil is prized for its high nutritional value due to the substantial amounts of triglycerides (TGs) and unsaturated fatty acids (FAs) present. While avocado oil is traditionally extracted from mature fruit flesh, alternative sources such as avocado seed oil have recently increased in popularity. Unfortunately, sufficient evidence is not available to support the claimed health benefit and safe use of such oils. To address potential quality issues and identify possible adulteration, authenticated avocado oils extracted from the fruit peel, pulp and seed by supercritical fluid extraction (SFE), as well as commercial avocado pulp and seed oils sold in US market were analyzed for TGs and FAs in the present study. Characterization and quantification of TGs were conducted using UHPLC/ESI-MS. Thirteen TGs containing saturated and unsaturated fatty acids in avocado oils were unambiguously identified. Compared to traditional analytical methods, which are based only on the relative areas of chromatographic peaks neglecting the differences in the relative response of individual TG, our method improved the quantification of TGs by using the reference standards whenever possible or the reference standards with the same equivalent carbon number (ECN). To verify the precision and accuracy of the UHPLC/ESI-MS method, the hydrolysis and transesterification products of avocado oil were analyzed for fatty acid methyl esters using a GC/MS method. The concentrations of individual FA were calculated, and the results agreed with the UHPLC/ESI-MS method. Although chemical profiles of avocado oils from pulp and peel are very similar, a significant difference was observed for the seed oil. Principal component analysis (PCA) based on TG and FA compositional data allowed correct identification of individual avocado oil and detection of possible adulteration.
Photocrosslinking of cDNA Display Molecules with Their Target Proteins as a New Strategy for Peptide Selection
Authors: Terai Takuya , Koike Tomoyuki , Nemoto Naoto
Published: April 2020

Binding peptides for given target molecules are often selected in vitro during drug discovery and chemical biology research. Among several display technologies for this purpose, complementary DNA (cDNA) display (a covalent complex of a peptide and its encoding cDNA linked via a specially designed puromycin-conjugated DNA) is unique in terms of library size, chemical stability, and flexibility of modification. However, selection of cDNA display libraries often suffers from false positives derived from non-specific binding. Although rigorous washing is a straightforward solution, this also leads to the loss of specific binders with moderate affinity because the interaction is non-covalent. To address this issue, herein, we propose a method to covalently link cDNA display molecules with their target proteins using light irradiation. We designed a new puromycin DNA linker that contains a photocrosslinking nucleic acid and prepared cDNA display molecules using the linker. Target proteins were also labeled with a short single-stranded DNA that should transiently hybridize with the linker. Upon ultraviolet (UV) light irradiation, cDNA display molecules encoding correct peptide aptamers made stable crosslinked products with the target proteins in solution, while display molecules encoding control peptides did not. Although further optimization and improvement is necessary, the results pave the way for efficient selection of peptide aptamers in multimolecular crowding biosystems.
Cellular Internalization of Beta-Carotene Loaded Polyelectrolyte Multilayer Capsules by Raman Mapping
Authors: Leopold Loredana F. , Marișca Oana , Oprea Ioana , Rugină Dumitrița , Suciu Maria , Nistor Mădălina , Tofană Maria , Leopold Nicolae , Coman Cristina
Published: April 2020

Raman mapping is becoming a very useful tool in investigating cells and cellular components, as well as bioactive molecules intracellularly. In this study, we have encapsulated beta-carotene using a layer-by-layer technique, as a way to enhance its stability and bioavailability. Further, we have used Raman mapping to characterize the as-obtained capsules and monitor their uptake by the human retinal epithelial D407 cells. We were able to successfully map the beta-carotene distribution inside the capsules, to localize the capsules intracellularly, and distinguish between capsules and other cellular components.
Protein Extraction, Enrichment and MALDI MS and MS/MS Analysis from Bitter Orange Leaves (Citrus aurantium)
Authors: Aiello Donatella , Siciliano Carlo , Mazzotti Fabio , Di Donna Leonardo , Risoluti Roberta , Napoli Anna
Published: April 2020

Citrus aurantium is a widespread tree in the Mediterranean area, and it is mainly used as rootstock for other citrus. In the present study, a vacuum infiltration centrifugation procedure, followed by solid phase extraction matrix-assisted laser desorption ionization tandem mass spectrometry (SPE MALDI MS/MS) analysis, was adopted to isolate proteins from leaves. The results of mass spectrometry (MS) profiling, combined with the top-down proteomics approach, allowed the identification of 78 proteins. The bioinformatic databases TargetP, SignalP, ChloroP, WallProtDB, and mGOASVM-Loc were used to predict the subcellular localization of the identified proteins. Among 78 identified proteins, 20 were targeted as secretory pathway proteins and 36 were predicted to be in cellular compartments including cytoplasm, nucleus, and cell membrane. The largest subcellular fraction was the secretory pathway, accounting for 25% of total proteins. Gene Ontology (GO) of Citrus sinensis was used to simplify the functional annotation of the proteins that were identified in the leaves. The Kyoto Encyclopedia of Genes and Genomes (KEGG) showed the enrichment of metabolic pathways including glutathione metabolism and biosynthesis of secondary metabolites, suggesting that the response to a range of environmental factors is the key processes in citrus leaves. Finally, the Lipase GDSL domain-containing protein GDSL esterase/lipase, which is involved in plant development and defense response, was for the first time identified and characterized in Citrus aurantium.
Special Issue: “Advances in Homogeneous Catalysis”
Authors: García-Álvarez Joaquín
Published: April 2020

The use of enzymes, organo-catalysts or transition metal catalysts, as opposed to the employment of stoichiometric quantities of other traditional promoters of different organic synthetic processes (like, inorganic/organic bases, Brønsted acids, radicals, etc.) has allowed the discovery of a great number of new synthetic protocols within the toolbox of organic chemists. Moreover, the employment of the aforementioned catalysts in organic synthesis permits: (i) the diminution of the global energy demand and production cost; (ii) the enhancement of both the chemoselectivity and stereoselectivity of the global process; and (iii) the reduction of metal-, organo- or bio-catalyst consumption, thanks to the possible recycling of the catalysts; all these being synthetic concepts closely related with the principles of so-called Green Chemistry. Thus, this Special Issue on “Advances in Homogenous Catalysis” has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of catalysis in organic synthesis (ranging from metal-, organo-, or bio-catalyzed organic reactions).
Enhanced Power Conversion Efficiency of Dye-Sensitized Solar Cells by Band Edge Shift of TiO2 Photoanode
Authors: Sung Hye Kyeong , Lee Yeonju , Kim Wook Hyun , Lee Sang-Ju , Sung Shi-Joon , Kim Dae-Hwan , Han Yoon Soo
Published: April 2020

By simple soaking titanium dioxide (TiO2) films in an aqueous Na2S solution, we could prepare surface-modified photoanodes for application to dye-sensitized solar cells (DSSCs). An improvement in both the open-circuit voltage (Voc) and the fill factor (FF) was observed in the DSSC with the 5 min-soaked photoanode, compared with those of the control cell without any modification. The UV–visible absorbance spectra, UPS valence band spectra, and dark current measurements revealed that the Na2S modification led to the formation of anions on the TiO2 surface, and thereby shifted the conduction band edge of TiO2 in the negative (upward) direction, inducing an increase of 29 mV in the Voc. It was also found that the increased FF value in the surface-treated device was attributed to an elevation in the shunt resistance.
Synthesis and Characterization of Silica-Coated Oxyhydroxide Aluminum/Doped Polymer Nanocomposites: A Comparative Study and Its Application as a Sorbent
Authors: A. Ahmed Inas , S. Hussein H. , H. Ragab Ahmed , S. Al-Radadi Najlaa
Published: April 2020

The present investigation is a comparison study of two nanocomposites: Nano-silica-coated oxyhydroxide aluminum (SiO2–AlOOH; SCB) and nano-silica-coated oxyhydroxide aluminum doped with polyaniline (SiO2–AlOOH–PANI; SBDP). The prepared nanocomposites were evaluated by monitoring the elimination of heavy metal Ni(II) ions from aquatic solutions. The synthesized nanocomposites were analyzed and described by applying scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) techniques, as well as Zeta potential distribution. In this study, two adsorbents were applied to investigate their adsorptive capacity to eliminate Ni(II) ions from aqueous solution. The obtained results revealed that SBDP nanocomposite has a higher negative zeta potential value (−47.2 mV) compared with SCB nanocomposite (−39.4 mV). The optimum adsorption was performed at pH 8, with approximately 94% adsorption for SCB and 97% adsorption for SBDP nanocomposites. The kinetics adsorption of Ni ions onto SCB and SBDP nanocomposites was studied by applying the pseudo first-order, pseudo second-order, and Mories–Weber models. The data revealed that the adsorption of Ni ions onto SCB and SBDP nanocomposites followed the pseudo second-order kinetic model. The equilibrium adsorption data were analyzed using three models: Langmuir, Freundlich, and Dubinin–Radusekevisch–Kanager Isotherm. It was concluded that the Langmuir isotherm fits the experimental results well for the SCB and SBDP nanocomposites. Thermodynamic data revealed that the adsorption process using SCB nanocomposites is an endothermic and spontaneous reaction. Meanwhile, the Ni ion sorption on SBDP nanocomposites is exothermic and spontaneous reaction.
Lysophosphatidic Acid Inhibits Simvastatin-Induced Myocytoxicity by Activating LPA Receptor/PKC Pathway
Authors: Won Kyung-Jong , Goh Yu-Jin , Hwang Sung-Hee
Published: April 2020

Statins such as simvastatin have many side effects, including muscle damage, which is known to be the most frequent undesirable side effect. Lysophosphatidic acid (LPA), a kind of biolipid, has diverse cellular activities, including cell proliferation, survival, and migration. However, whether LPA affects statin-linked muscle damage has not been reported yet. In the present study, to determine whether LPA might exert potential protective effect on statin-induced myocyotoxicity, the effect of LPA on cytotoxicity in rat L6 myoblasts exposed to simvastatin was explored. Viability and apoptosis of rat L6 myoblasts were detected via 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5- [(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Protein expression levels were detected via Western blotting. Simvastatin decreased viability of L6 cells. Such decrease in viability was recovered in the presence of LPA. Treatment with LPA suppressed simvastatin-induced apoptosis in L6 cells. In addition, treatment with LPA receptor inhibitor Ki16425, protein kinase C (PKC) inhibitor GF109203X, or intracellular calcium chelator BAPTA-AM attenuated the recovery effect of LPA on simvastatin-induced L6 cell toxicity. These findings indicate that LPA may inhibit simvastatin-induced toxicity in L6 cells probably by activating the LPA receptor-PKC pathway. Therefore, LPA might have potential as a bioactive molecule to protect muscles against simvastatin-induced myotoxicity.
Antiplasmodial Activity of p-Substituted Benzyl Thiazinoquinone Derivatives and Their Potential against Parasitic Infections
Authors: Casertano Marcello , Menna Marialuisa , Fattorusso Caterina , Basilico Nicoletta , Parapini Silvia , Persico Marco , Imperatore Concetta
Published: April 2020

Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure–activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the para position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested p-benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold.
Structure and Properties of Biodegradable Poly (Xylitol Sebacate-Co-Butylene Sebacate) Copolyester
Authors: Piątek-Hnat Marta , Bomba Kuba , Pęksiński Jakub
Published: April 2020

In this work, a bio-based copolyester with good mechanical properties was synthesized and characterized in terms of structure, main properties and biodegradability Determining the chemical structure of such materials is important to understand their behavior and properties. Performing an extraction of insoluble cross-linked polymer using different solvents allowed us to analyze how the polymer behaves when subjected to different chemical environments, and to obtain soluble samples suitable for more in-depth analysis. Chemical structure of poly (xylitol sebacate-co-butylene sebacate) was determined by a 1H NMR and FTIR analysis of both prepolymer gel sample and samples obtained by extraction of cross-linked polymer using different solvents. Block structure of the copolymer was confirmed by both NMR and DSC. Gel fraction, swelling value, water contact angle, and mechanical properties were also analyzed. Biodegradability of this material was confirmed by performing enzymatic and hydrolytic degradation. Synthesizing sugar-alcohol based copolyester using three monomers leads to obtaining a material with interesting chemical structure and desirable mechanical properties comparable to conventional elastomers.
Preparation of Nanocellulose Using Ionic Liquids: 1-Propyl-3-Methylimidazolium Chloride and 1-Ethyl-3-Methylimidazolium Chloride
Authors: Babicka Marta , Woźniak Magdalena , Dwiecki Krzysztof , Borysiak Sławomir , Ratajczak Izabela
Published: April 2020

Cellulose nanocrystals were prepared using ionic liquids (ILs), 1-ethyl-3-methylimidazolium chloride [EMIM][Cl] and 1-propyl-3-methylimidazolium chloride [PMIM][Cl], from microcrystalline cellulose. The resultant samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The XRD results showed that nanocellulose obtained by treatment with both ILs preserved basic cellulose I structure, but crystallinity index of samples (except for Sigmacell treated with [EMIM][Cl]) was lower in comparison to the starting microcrystalline cellulose. The DLS results indicated noticeably smaller particle sizes of prepared cellulose for material treated with [PMIM][Cl] compared to cellulose samples hydrolyzed with [EMIM][Cl], which were prone to agglomeration. The obtained nanocellulose had a rod-like structure that was confirmed by electron microscopy analyses. Moreover, the results described in this paper indicate that cation type of ILs influences particle size and morphology of cellulose after treatment with ionic liquids.
Determination of Glyphosate in Dried Wheat by 1H-NMR Spectroscopy
Authors: Shumilina Elena , Andreasen Christian , Bitarafan Zahra , Dikiy Alexander
Published: April 2020

A wheat field was sprayed with a dosage of 1.1 kg a.i./ha Roundup PowerMax 10 days before harvest. The 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used for the detection and quantification of the glyphosate (GLYP) in dried wheat spikelets, leaves, and stems. The quantification was done by the integration of the CH2-P groups doublet at 3.00 ppm with good linearity. The GLYP content varied between different samples and parts of the plant. On average, the largest content of herbicide was found in leaves (20.0 mg/kg), followed by stems (6.4 mg/kg) and spikelets (6.3 mg/kg). Our study shows that the 1H-NMR spectroscopy can be a rapid and reliable tool for GLYP detection and quantification in the field studies.
Anti-Allergic and Anti-Inflammatory Effects of Undecane on Mast Cells and Keratinocytes
Authors: Choi Dabin , Kang Wesuk , Park Taesun
Published: April 2020

The critical roles of keratinocytes and resident mast cells in skin allergy and inflammation have been highlighted in many studies. Cyclic adenosine monophosphate (cAMP), the intracellular second messenger, has also recently emerged as a target molecule in the immune reaction underlying inflammatory skin conditions. Here, we investigated whether undecane, a naturally occurring plant compound, has anti-allergic and anti-inflammatory activities on sensitized rat basophilic leukemia (RBL-2H3) mast cells and HaCaT keratinocytes and we further explored the potential involvement of the cAMP as a molecular target for undecane. We confirmed that undecane increased intracellular cAMP levels in mast cells and keratinocytes. In sensitized mast cells, undecane inhibited degranulation and the secretion of histamine and tumor necrosis factor α (TNF-α). In addition, in sensitized keratinocytes, undecane reversed the increased levels of p38 phosphorylation, nuclear factor kappaB (NF-κB) transcriptional activity and target cytokine/chemokine genes, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and interleukin-8 (IL-8). These results suggest that undecane may be useful for the prevention or treatment of skin inflammatory disorders, such as atopic dermatitis, and other allergic diseases.
Essential Oils Extracted from Different Species of the Lamiaceae Plant Family as Prospective Bioagents against Several Detrimental Pests
Authors: Ebadollahi Asgar , Ziaee Masumeh , Palla Franco
Published: April 2020

On the basis of the side effects of detrimental synthetic chemicals, introducing healthy, available, and effective bioagents for pest management is critical. Due to this circumstance, several studies have been conducted that evaluate the pesticidal potency of plant-derived essential oils. This review presents the pesticidal efficiency of essential oils isolated from different genera of the Lamiaceae family including Agastache Gronovius, Hyptis Jacquin, Lavandula L., Lepechinia Willdenow, Mentha L., Melissa L., Ocimum L., Origanum L., Perilla L., Perovskia Kar., Phlomis L., Rosmarinus L., Salvia L., Satureja L., Teucrium L., Thymus L., Zataria Boissier, and Zhumeria Rech. Along with acute toxicity, the sublethal effects were illustrated such as repellency, antifeedant activity, and adverse effects on the protein, lipid, and carbohydrate contents, and on the esterase and glutathione S-transferase enzymes. Chemical profiles of the introduced essential oils and the pesticidal effects of their main components have also been documented including terpenes (hydrocarbon monoterpene, monoterpenoid, hydrocarbon sesquiterpene, and sesquiterpenoid) and aliphatic phenylpropanoid. Consequently, the essential oils of the Lamiaceae plant family and their main components, especially monoterpenoid ones with several bioeffects and multiple modes of action against different groups of damaging insects and mites, are considered to be safe, available, and efficient alternatives to the harmful synthetic pesticides.
Antimalarial Agents as Therapeutic Tools Against Toxoplasmosis—A Short Bridge between Two Distant Illnesses
Authors: Secrieru Alina , Costa Inês C. C. , O'Neill Paul M. , Cristiano Maria L. S.
Published: April 2020

Toxoplasmosis is an infectious disease with paramount impact worldwide, affecting many vulnerable populations and representing a significant matter of concern. Current therapies used against toxoplasmosis are based essentially on old chemotypes, which fail in providing a definitive cure for the disease, placing the most sensitive populations at risk for irreversible damage in vital organs, culminating in death in the most serious cases. Antimalarial drugs have been shown to possess key features for drug repurposing, finding application in the treatment of other parasite-borne illnesses, including toxoplasmosis. Antimalarials provide the most effective therapeutic solutions against toxoplasmosis and make up for the majority of currently available antitoxoplasmic drugs. Additionally, other antiplasmodial drugs have been scrutinized and many promising candidates have emanated in recent developments. Available data demonstrate that it is worthwhile to explore the activity of classical and most recent antimalarial chemotypes, such as quinolines, endoperoxides, pyrazolo[1,5-a]pyrimidines, and nature-derived peptide-based parasiticidal agents, in the context of toxoplasmosis chemotherapy, in the quest for encountering more effective and safer tools for toxoplasmosis control or eradication.
Model Optimization for the Prediction of Red Wine Phenolic Compounds Using Ultraviolet–Visible Spectra
Authors: Beaver Chris , Collins Thomas S , Harbertson James
Published: April 2020

The primary objective of this work was to optimize red wine phenolic prediction with models built from wine ultraviolet–visible absorbance spectra. Three major obstacles were addressed to achieve this, namely algorithm selection, spectral multicollinearity, and phenolic evolution over time. For algorithm selection, support vector regression, kernel ridge regression, and kernel partial least squares regression were compared. For multicollinearity, the spectrum of malvidin chloride was used as an external standard for spectral adjustment. For phenolic evolution, spectral data were collected during fermentation as well as once a week for four weeks after fermentation had ended. Support vector regression gave the most accurate predictions among the three algorithms tested. Additionally, malvidin chloride proved a useful standard for phenolic spectral transformation and isolation. As for phenolic evolution, models needed to be calibrated and validated throughout the aging process to ensure predictive accuracy. In short, red wine phenolic prediction by the models built in this work can be realistically achieved, although periodic model re-calibration and expansion from data obtained using known phenolic assays is recommended to maintain model accuracy.
Sedative Effects of Latexes Obtained from Some Lactuca L. Species Growing in Turkey
Authors: Ilgün Selen , Küpeli Akkol Esra , Ilhan Mert , Çiçek Polat Derya , Baldemir Kılıç Ayse , Coşkun Maksut , Sobarzo-Sánchez Eduardo
Published: April 2020

Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as “lettuce oil” and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Panćić) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (lactucin, lactucopicrin, 11,13β-dihydrolactucin, and 11,13β-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.
Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent
Authors: Hanh Bui Thi Bich , Park June-Woo , Kim Tae Ho , Kim Jae-Sung , Yang Chul-Su , Jang Kiseok , Cui Jinsheng , Oh Dong-Chan , Jang Jichan
Published: April 2020

Mycobacterium abscessus is the most difficult-to-treat nontuberculous mycobacteria because of its resistance to many antibiotics. In this study, we screened the Korea Chemical Bank library for a bioluminescent reporter assay to identify molecules capable of acting against M. abscessus. On application of the assay, rifamycin O showed excellent in vitro activity with a narrow range of the minimum inhibitory concentration required to inhibit the growth of 90% of the bacterium (MIC90 = 4.0–6.2 μM); its in vivo efficacy in the zebrafish (Danio rerio) infection model was comparable to that of rifabutin at 25 μM. Furthermore, rifamycin O did not show significant toxicity in cells and the zebrafish model. These results are the first in vivo indication that rifamycin O may be a drug candidate for treating M. abscessus infections.
A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats
Authors: Ezzeldin Essam , Iqbal Muzaffar , Asiri Yousif A. , Ali Azza A , Alam Prawez , El-Nahhas Toqa
Published: April 2020

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid–liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.
Analysis of Volatile Components in Different Ophiocordyceps sinensis and Insect Host Products
Authors: Qiu Xuehong , Cao Li , Han Richou
Published: April 2020

The artificial production of Ophiocordyceps sinensis mycelia and fruiting bodies and the Chinese cordyceps has been established. However, the volatile components from these O. sinensis products are not fully identified. An efficient, convenient, and widely used approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography and quadrupole time-of-flight mass spectrometry (GC×GC-QTOFMS) was developed for the extraction and the analysis of volatile compounds from three categories of 16 products, including O. sinensis fungus, Thitarodes hosts of O. sinensis, and the Chinese cordyceps. A total of 120 volatile components including 36 alkanes, 25 terpenes, 17 aromatic hydrocarbons, 10 ketones, 5 olefines, 5 alcohols, 3 phenols, and 19 other compounds were identified. The contents of these components varied greatly among the products but alkanes, especially 2,5,6-trimethyldecane, 2,3-dimethylundecane and 2,2,4,4-tetramethyloctane, are the dominant compounds in general. Three categories of volatile compounds were confirmed by partial least squares-discriminant analysis (PLS-DA). This study provided an ideal method for characterizing and distinguishing different O. sinensis and insect hosts-based products.
Palstimolide A: A Complex Polyhydroxy Macrolide with Antiparasitic Activity
Authors: Keller Lena , Siqueira-Neto Jair L. , Souza Julia M. , Eribez Korina , LaMonte Gregory M. , Smith Jennifer E. , Gerwick William H.
Published: April 2020

Marine Cyanobacteria (blue-green algae) have been shown to possess an enormous potential to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Here, we report the isolation and structure determination of palstimolide A, a complex polyhydroxy macrolide with a 40-membered ring that was isolated from a tropical marine cyanobacterium collected at Palmyra Atoll. NMR-guided fractionation in combination with MS2-based molecular networking and isolation via HPLC yielded 0.7 mg of the pure compound. The small quantity isolated along with the presence of significant signal degeneracy in both the 1H and 13C-NMR spectra complicated the structure elucidation of palstimolide A. Various NMR experiments and solvent systems were employed, including the LR-HSQMBC experiment that allows the detection of long-range 1H–13C correlation data across 4-, 5-, and even 6-bonds. This expanded NMR data set enabled the elucidation of the palstimolide’s planar structure, which is characterized by several 1,5-disposed hydroxy groups as well as a tert-butyl group. The compound showed potent antimalarial activity with an IC50 of 223 nM as well as interesting anti-leishmanial activity with an IC50 of 4.67 µM.
Chitosan-Based Agronanochemicals as a Sustainable Alternative in Crop Protection
Authors: Maluin Farhatun Najat , Hussein Mohd Zobir
Published: April 2020

The rise in the World’s food demand in line with the increase of the global population has resulted in calls for more research on the production of sustainable food and sustainable agriculture. A natural biopolymer, chitosan, coupled with nanotechnology could offer a sustainable alternative to the use of conventional agrochemicals towards a safer agriculture industry. Here, we review the potential of chitosan-based agronanochemicals as a sustainable alternative in crop protection against pests, diseases as well as plant growth promoters. Such effort offers better alternatives: (1) the existing agricultural active ingredients can be encapsulated into chitosan nanocarriers for the formation of potent biocides against plant pathogens and pests; (2) the controlled release properties and high bioavailability of the nanoformulations help in minimizing the wastage and leaching of the agrochemicals’ active ingredients; (3) the small size, in the nanometer regime, enhances the penetration on the plant cell wall and cuticle, which in turn increases the argochemical uptake; (4) the encapsulation of agrochemicals in chitosan nanocarriers shields the toxic effect of the free agrochemicals on the plant, cells and DNA, thus, minimizing the negative impacts of agrochemical active ingredients on human health and environmental wellness. In addition, this article also briefly reviews the mechanism of action of chitosan against pathogens and the elicitations of plant immunity and defense response activities of chitosan-treated plants.
Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues
Authors: Adamus-Grabicka Angelika A. , Markowicz-Piasecka Magdalena , Cieślak Marcin , Królewska-Golińska Karolina , Hikisz Paweł , Kusz Joachim , Małecka Magdalena , Budzisz Elzbieta
Published: April 2020

A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds’ activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.
Study of the Quality Parameters and the Antioxidant Capacity for the FTIR-Chemometric Differentiation of Pistacia Vera Oils
Authors: Valasi Lydia , Arvanitaki Dimitra , Mitropoulou Angeliki , Georgiadou Maria , Pappas Christos S.
Published: April 2020

The aim of this work was to characterize the pistachio oil of the Greek variety, “Aegina”, evaluate its various quality indices, and investigate the potential use of FTIR as a tool to discriminate different oil qualities. For this purpose, the antioxidant capacity, the tocopherol content and the oxidation and degradation of fatty acids, as described by k, Δk, R-values, and free acidity were evaluated using 45 samples from eight different areas of production and two subsequent years of harvesting. The antioxidant capacity was estimated using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazine (DPPH) assays, and the tocopherol content was quantified through HPLC analysis. FTIR spectra were recorded for all samples and multivariate analysis was applied. The results showed significant differences between the oil samples of different harvesting years, which were successfully discriminated by a representative FTIR spectral region based on R-value, total antioxidant capacity, and scavenging capacity, through ABTS. A similar approach could not be confirmed for the other quality parameters, such as the free acidity and the tocopherol content. This research highlighted the possibility of developing a simple, rapid, economic, and environment friendly method for the discrimination of pistachio oils according to their quality profile, through FTIR spectroscopy and multivariate analysis.
Computational Study of Drugs Targeting Nuclear Receptors
Authors: Kenda Maša , Sollner Dolenc Marija
Published: April 2020

Endocrine-disrupting chemicals have been shown to interfere with the endocrine system function at the level of hormone synthesis, transport, metabolism, binding, action, and elimination. They are associated with several health problems in humans: obesity, diabetes mellitus, infertility, impaired thyroid and neuroendocrine functions, neurodevelopmental problems, and cancer are among them. As drugs are chemicals humans can be frequently exposed to for longer periods of time, special emphasis should be put on their endocrine-disrupting potential. In this study, we conducted a screen of 1046 US-approved and marketed small-molecule drugs (molecular weight between 60 and 600) for estimating their endocrine-disrupting properties. Binding affinity to 12 nuclear receptors was assessed with a molecular-docking program, Endocrine Disruptome. We identified 130 drugs with a high binding affinity to a nuclear receptor that is not their pharmacological target. In a subset of drugs with predicted high binding affinities to a nuclear receptor with Endocrine Disruptome, the positive predictive value was 0.66 when evaluated with in silico results obtained with another molecular docking program, VirtualToxLab, and 0.32 when evaluated with in vitro results from the Tox21 database. Computational screening was proven useful in prioritizing drugs for in vitro testing. We suggest that the novel interactions of drugs with nuclear receptors predicted here are further investigated.
Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
Authors: Acar Çevik Ulviye , Kaya Çavuşoğlu Betül , Sağlık Begüm Nurpelin , Osmaniye Derya , Levent Serkan , Ilgın Sinem , Özkay Yusuf , Kaplancıklı Zafer Asım
Published: April 2020

In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthesized and studied as potent aromatase inhibitors. First, these compounds were tested for their anti-cancer properties against human breast cancer cell line (MCF-7). The most active compounds 5c, 5e, 5k, and 5m on MCF-7 cell line were subject to further in vitro aromatase enzyme inhibition assays to determine the possible mechanisms of action underlying their activity. Compound 5e showed slight less potent aromatase inhibitory activity than that of letrozole with IC50 = 0.032 ± 0.042 µM, compared to IC50 = 0.024 ± 0.001 µM for letrozole. Furthermore, compound 5e and reference drug letrozole were docked into human placental aromatase enzyme to predict their possible binding modes with the enzyme. Finally, ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds (5a–5p) were calculated by QikProp 4.8 software.
Mapping Mediterranean Forest Plant Associations and Habitats with Functional Principal Component Analysis Using Landsat 8 NDVI Time Series
Authors: Pesaresi Simone , Mancini Adriano , Quattrini Giacomo , Casavecchia Simona
Published: April 2020

The classification of plant associations and their mapping play a key role in defining habitat biodiversity management, monitoring, and conservation strategies. In this work we present a methodological framework to map Mediterranean forest plant associations and habitats that relies on the application of the Functional Principal Component Analysis (FPCA) to the remotely sensed Normalized Difference Vegetation Index (NDVI) time series. FPCA, considering the chronological order of the data, reduced the NDVI time series data complexity and provided (as FPCA scores) the main seasonal NDVI phenological variations of the forests. We performed a supervised classification of the FPCA scores combined with topographic and lithological features of the study area to map the forest plant associations. The supervised mapping achieved an overall accuracy of 87.5%. The FPCA scores contributed to the global accuracy of the map much more than the topographic and lithological features. The results showed that (i) the main seasonal phenological variations (FPCA scores) are effective spatial predictors to obtain accurate plant associations and habitat maps; (ii) the FPCA is a suitable solution to simultaneously express the relationships between remotely sensed and ecological field data, since it allows us to integrate these two different perspectives about plant associations in a single graph. The proposed approach based on the FPCA is useful for forest habitat monitoring, as it can contribute to produce periodically detailed vegetation-based habitat maps that reflect the “current” status of vegetation and habitats, also supporting the study of plant associations.
Gait Rhythm Dynamics for Neuro-Degenerative Disease Classification via Persistence Landscape- Based Topological Representation
Authors: Yan Yan , Ivanov Kamen , Mumini Omisore Olatunji , Igbe Tobore , Liu Qiuhua , Nie Zedong , Wang Lei
Published: April 2020

Neuro-degenerative disease is a common progressive nervous system disorder that leads to serious clinical consequences. Gait rhythm dynamics analysis is essential for evaluating clinical states and improving quality of life for neuro-degenerative patients. The magnitude of stride-to-stride fluctuations and corresponding changes over time—gait dynamics—reflects the physiology of gait, in quantifying the pathologic alterations in the locomotor control system of health subjects and patients with neuro-degenerative diseases. Motivated by algebra topology theory, a topological data analysis-inspired nonlinear framework was adopted in the study of the gait dynamics. Meanwhile, the topological representation–persistence landscapes were used as input of classifiers in order to distinguish different neuro-degenerative disease type from healthy. In this work, stride-to-stride time series from healthy control (HC) subjects are compared with the gait dynamics from patients with amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and Parkinson’s disease (PD). The obtained results show that the proposed methodology discriminates healthy subjects from subjects with other neuro-degenerative diseases with relatively high accuracy. In summary, our study is the first attempt to provide a topological representation-based method into the disease classification with gait rhythms measured from the stride intervals to visualize gait dynamics and classify neuro-degenerative diseases. The proposed method could be potentially used in earlier interventions and state monitoring.
The Prediction of Batting Averages in Major League Baseball
Authors: Bailey Sarah R. , Loeppky Jason , Swartz Tim B.
Published: April 2020

The prediction of yearly batting averages in Major League Baseball is a notoriously difficult problem where standard errors using the well-known PECOTA (Player Empirical Comparison and Optimization Test Algorithm) system are roughly 20 points. This paper considers the use of ball-by-ball data provided by the Statcast system in an attempt to predict batting averages. The publicly available Statcast data and resultant predictions supplement proprietary PECOTA forecasts. With detailed Statcast data, we attempt to account for a luck component involving batting averages. It is anticipated that the luck component will not be repeated in future seasons. The two predictions (Statcast and PECOTA) are combined via simple linear regression to provide improved forecasts of batting average.
Short-Term Effects of Different Straw Returning Methods on the Soil Physicochemical Properties and Quality Index in Dryland Farming in NE China
Authors: Fan Wei , Wu Jinggui , Ahmed Sharaf , Hu Juan , Chen Xiaodong , Li Xiaohang , Zhu Wenyue , Opoku-Kwanowaa Yaa
Published: April 2020

A field experiment was designed to assess the impacts of various maize straw (stover) returning methods on the basic soil physicochemical properties and soil quality index in Jilin (NE China). The five treatments were no return of straw residues (CK), straw incorporated evenly into the soil using the crashing-ridging technique (EIS), straw mulching (SM), straw plowed into the soil (SP), and straw returned in granulated form (SG). Relative to the no straw return, EIS effectively reduced soil bulk density and penetration resistance, increased soil total organic carbon (TOC), macroaggregate-associated carbon content, and the accumulation of soil humus. Furthermore, EIS improved soil structure and soil aggregate stability and significantly increased the soil quality index. Among the various straw returning treatments, SM and SG significantly promoted soil macroaggregation and increased macroaggregate-associated carbon content by 23.69% and 21.70% at the soil surface, respectively (as compared with the control). Compared to SM, SP, and SG, EIS significantly enhanced the aliphaticity and hydrophobicity of soil organic carbon. These results suggested that EIS was the most efficient straw return mode to increase TOC and improve soil structure and fertility.