bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Initial Conformation on the Starch Biopolymer Film Formation Studied by NMR
Authors: Ghoshal Sushanta , Mattea Carlos , Denner Paul , Stapf Siegfried
Published: March 2020

The formation of a rigid porous biopolymer scaffold from aqueous samples of 1% w/v (suspension) and 5% w/v (gel) corn starch was studied using optical and nuclear magnetic resonance (NMR) techniques. The drying process of these systems was observed using a single-sided NMR scanner by application of the Carr–Purcell–Meiboom–Gill pulse sequence at different layer positions. The echo decays were analyzed and spin–spin relaxation times (T2) were obtained for each layer. From the depth dependent T2 relaxation time study, it was found that the molecular mobility of water within the forming porous matrix of these two samples varied notably at different stages of film formation. At an intermediate stage, a gradual decrease in mobility of the emulsion sample towards the air–sample interface was observed, while the gel sample remained homogeneous all along the sample height. At a later stage of drying, heterogeneity in the molecular dynamics was observed in both samples showing low mobility at the bottom part of the sample. A wide-angle X-ray diffraction study confirmed that the structural heterogeneity persisted in the final film obtained from the 5% corn starch aqueous sample, whereas the film obtained from the 1% corn starch in water was structurally homogeneous.
Synthesis of Functionalized Indoles via Palladium-Catalyzed Cyclization of N-(2-allylphenyl) Benzamide: A Method for Synthesis of Indomethacin Precursor
Authors: Chang Zhe , Ma Tong , Zhang Yu , Dong Zheng , Zhao Heng , Zhao Depeng
Published: March 2020

We developed an efficient method for synthesis of substituted N-benzoylindole via Pd(II)-catalyzed C–H functionalization of substituted N-(2-allylphenyl)benzamide. The reaction showed a broad substrate scope (including N-acetyl and N-Ts substrates) and substituted indoles were obtained in good to excellent yields. The most distinctive feature of this method lies in the high selectivity for N-benzoylindole over benzoxazine, and this is the first example of Pd(II)-catalyzed synthesis of substituted N-benzoylindole. Notably, this new method was applied for the synthesis of key intermediate of indomethacin.
Synthesis and Biological Evaluation of a Novel C8-Pyrrolobenzodiazepine (PBD) Adenosine Conjugate. A Study on the Role of the PBD Ring in the Biological Activity of PBD-Conjugates
Authors: Ferguson Lindsay , Bhakta Sanjib , Fox Keith R. , Wells Geoff , Brucoli Federico
Published: March 2020

Here we sought to evaluate the contribution of the PBD unit to the biological activity of PBD-conjugates and, to this end, an adenosine nucleoside was attached to the PBD A-ring C8 position. A convergent approach was successfully adopted for the synthesis of a novel C8-linked pyrrolo(2,1-c)(1,4)benzodiazepine(PBD)-adenosine(ADN) hybrid. The PBD and adenosine (ADN) moieties were synthesized separately and then linked through a pentynyl linker. To our knowledge, this is the first report of a PBD connected to a nucleoside. Surprisingly, the compound showed no cytotoxicity against murine cells and was inactive against Mycobacterium aurum and M. bovis strains and did not bind to guanine-containing DNA sequences, as shown by DNase I footprinting experiments. Molecular dynamics simulations revealed that the PBD–ADN conjugate was poorly accommodated in the DNA minor groove of two DNA sequences containing the AGA-PBD binding motif, with the adenosine moiety of the ligand preventing the covalent binding of the PBD unit to the guanine amino group of the DNA duplex. These interesting findings shed further light on the ability of the substituents attached at the C8 position of PBDs to affect and modulate the biological and biophysical properties of PBD hybrids.
On Column Binding a Real-Time Biosensor for β-lactam Antibiotics Quantification
Authors: Abdullah Shahla M. , Rachid Shwan
Published: March 2020

This work aimed to develop accurate, quick, and practical tools for the detection of residues of penicillin G antibiotic in biological and non-biological samples. The assays were developed based on the binding mechanism of β-lactam to penicillin-binding proteins; samples of different concentrations of penicillin G were incubated with in vitro expressed 6X-Histidine-tagged soluble penicillin-binding protein (PBP2x*) of Streptococcus pneumoniae (S. pneumoniae), whereby penicillin G in samples specifically binds to PBP2x*. The fluorescent-labeled β-lactam analogue Bocillin FL was used as a competent substrate, and two different routes estimated the amounts of the penicillin G. The first route was established based on the differences in the concentration of non-bounded Bocillin FL molecules within the reactions while using a real-time polymerase chain reaction (PCR)-based method for fluorescence detection. The second route depended on the amount of the relative intensity of Bocillin FL bounded to Soluble PBP-2x*, being run on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-page), visualized by a ChemiDoc-It®2 Imager, and quantified based on the fluorescence affinity of the competent substrate. While both of the methods gave a broad range of linearity and high sensitivity, the on column based real-time method is fast, non-time consuming, and highly sensitive. The method identified traces of antibiotic in the range 0.01–0.2 nM in addition to higher accuracy in comparison to the SDS-based detection method, while the sensitivity of the SDS-based method ranged between 0.015 and 2 µM). Thus, the on column based real time assay is a fast novel method, which was developed for the first time based on the binding inhibition of a fluorescence competitor material and it can be adapted to screen traces of penicillin G in any biological and environmental samples.
Enhancement of Macarpine Production in Eschscholzia Californica Suspension Cultures under Salicylic Acid Elicitation and Precursor Supplementation
Authors: Balažová Andrea , Urdová Júlia , Forman Vladimír , Mučaji Pavel
Published: March 2020

Macarpine is a minor benzophenanthridine alkaloid with interesting biological activities, which is produced in only a few species of the Papaveraceae family, including Eschscholzia californica. Our present study was focused on the enhancement of macarpine production in E. californica suspension cultures using three elicitation models: salicylic acid (SA) (4; 6; 8 mg/L) elicitation, and simultaneous or sequential combinations of SA and L-tyrosine (1 mmol/L). Sanguinarine production was assessed along with macarpine formation in elicited suspension cultures. Alkaloid production was evaluated after 24, 48 and 72 h of elicitation. Among the tested elicitation models, the SA (4 mg/L), supported by L-tyrosine, stimulated sanguinarine and macarpine production the most efficiently. While sequential treatment led to a peak accumulation of sanguinarine at 24 h and macarpine at 48 h, simultaneous treatment resulted in maximum sanguinarine accumulation at 48 h and macarpine at 72 h. The effect of SA elicitation and precursor supplementation was evaluated also based on the gene expression of 4′-OMT, CYP719A2, and CYP719A3. The gene expression of investigated enzymes was increased at all used elicitation models and their changes correlated with sanguinarine but not macarpine accumulation.
Separation and Characterization of Phenolamines and Flavonoids from Rape Bee Pollen, and Comparison of Their Antioxidant Activities and Protective Effects Against Oxidative Stress
Authors: Zhang Huifang , Liu Rui , Lu Qun
Published: March 2020

Phenolamines and flavonoids are two important components in bee pollen. There are many reports on the bioactivity of flavonoids in bee pollen, but few on phenolamines. This study aims to separate and characterize the flavonoids and phenolamines from rape bee pollen, and compare their antioxidant activities and protective effects against oxidative stress. The rape bee pollen was separated to obtain 35% and 50% fractions, which were characterized by HPLC-ESI-QTOF-MS/MS. The results showed that the compounds in 35% fraction were quercetin and kaempferol glycosides, while the compounds in 50% fraction were phenolamines, including di-p-coumaroyl spermidine, p-coumaroyl caffeoyl hydroxyferuloyl spermine, di-p-coumaroyl hydroxyferuloyl spermine, and tri-p-coumaroyl spermidine. The antioxidant activities of phenolamines and flavonoids were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays. It was found that the antioxidant activity of phenolamines was significantly higher than that of flavonoids. Moreover, phenolamines showed better protective effects than flavonoids on HepG2 cells injured by AAPH. Furthermore, phenolamines could significantly reduce the reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and increase the superoxide dismutase (SOD) and glutathione (GSH) levels. This study lays a foundation for the further understanding of phenolamines in rape bee pollen.
Comparative Studies on Polysaccharides, Triterpenoids, and Essential Oil from Fermented Mycelia and Cultivated Sclerotium of a Medicinal and Edible Mushroom, Poria Cocos
Authors: Wang Dongdong , Huang Chonggui , Zhao Ye , Wang Lin , Yang Yongcheng , Wang Anhua , Zhang Yang , Hu Gaosheng , Jia Jingming
Published: March 2020

Poria cocos, an important medicinal and edible fungus, is well known in East Asia. The main active components are water-soluble polysaccharides (WPS) and triterpenoids. Due to the growing market demand, long cultivation period, and consumption of pine trunk during cultivation, alternative methods for producing P. cocos or its active components should be investigated. In this study, WPS, triterpenoids, monosaccharide composition, and essential oil in fermented mycelia and cultivated sclerotium were analyzed using UV spectrophotometry, HPLC, pre-column derivatization, and HS-GC/MS, respectively. Our results showed that the WPS and triterpenoids in mycelia are several times higher than those in sclerotium. Among the 62 compounds identified by HS-GC/MS analysis from the essential oil obtained from the fermentation media and a fresh external layer, the two main fragrances in common were linalool and methyl phenylacetate. Our results suggested that it is applicable to produce polysaccharides and triterpenoids by the fermentation of P. cocos, and a strategy to improve triterpenoid production in the fermentation process was proposed.
Structure and Dynamics of the Superprotonic Conductor Caesium Hydrogen Sulfate, CsHSO4
Authors: Parker Stewart F. , Cavaye Hamish , Callear Samantha K.
Published: March 2020

We have investigated caesium hydrogen sulfate, CsHSO4, in all three of its ambient pressure phases by total scattering neutron diffraction, inelastic neutron scattering (INS) and Raman spectroscopies and periodic density functional theory calculations. Above 140 °C, CsHSO4 undergoes a phase transition to a superprotonic conductor that has potential application in intermediate temperature fuel cells. Total scattering neutron diffraction data clearly show that all the existing structures of this phase are unable to describe the local structure, because they have either partial occupancies of the atoms and/or non-physical O–H distances. Knowledge of the local structure is crucial because it is this that determines the conduction mechanism. Starting from one of the previous models, we have generated a new structure that has no partial occupancies and reasonable O–H distances. After geometry optimisation, the calculated radial distribution function is in reasonable agreement with the experimental data, as are the calculated and observed INS and Raman spectra. This work is particularly notable in that we have measured INS spectra in the O–H stretch region above room temperature, which is extremely rare. The INS spectra have the enormous advantage that the electrical anharmonicity that complicates the infrared spectra is absent and the stretch modes are plainly seen.
Dissolution Behavior of Flufenamic Acid in Heated Mixtures with Nanocellulose
Authors: Mantas Athanasios , Mihranyan Albert
Published: March 2020

Flufenamic acid (FFA) is a problem drug that has up to eight different polymorphs and shows poor solubility. Variability in bioavailability has been reported in the past resulting in limited use of FFA in the oral solid dosage form. The goal of this article was to investigate the polymorphism and amorphization behavior of FFA in non-heated and heated mixtures with high surface area nanocellulose, i.e., Cladophora cellulose (CLAD). As a benchmark, low surface area microcrystalline cellulose (MCC) was used. The solid-state properties of mixtures were characterized with X-ray diffraction, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The dissolution behavior of mixtures was studied in three biorelevant media, i.e., fasted state simulated gastric fluid, fasted state simulated intestinal fluid, and fed state simulated intestinal fluid. Additional thermal analysis and dissolution tests were carried out following 4 months of storage at 75% RH and room temperature. Heated mixtures of FFA with CLAD resulted in complete amorphization of the drug, whereas that with MCC produced a mixture of up to four different polymorphs. The amorphous FFA mixture with CLAD exhibited rapid and invariable fasted/fed state dissolution in simulated intestinal fluids, whereas that of MCC mixtures was highly dependent on the biorelevant medium. The storage of the heated FFA-CLAD mixture did not result in recrystallization or changes in dissolution profile, whereas heated FFA-MCC mixture showed polymorphic changes. The straightforward dry powder formulation strategy presented here bears great promise for reformulating a number of problem drugs to enhance their dissolution properties and reduce the fasted/fed state variability.
Thermal Behavior of Green Cellulose-Filled Thermoplastic Elastomer Polymer Blends
Authors: Cichosz Stefan , Masek Anna
Published: March 2020

A recently developed cellulose hybrid chemical treatment consists of two steps: solvent exchange (with ethanol or hexane) and chemical grafting of maleic anhydride (MA) on the surface of fibers. It induces a significant decrease in cellulose moisture content and causes some changes in the thermal resistance of analyzed blend samples, as well as surface properties. The thermal characteristics of ethylene-norbornene copolymer (TOPAS) blends filled with hybrid chemically modified cellulose fibers (UFC100) have been widely described on the basis of differential scanning calorimetry and thermogravimetric analysis. Higher thermal stability is observed for the materials filled with the fibers which were dried before any of the treatments carried out. Dried cellulose filled samples start to degrade at approximately 330 °C while undried UFC100 specimens begin to degrade around 320 °C. Interestingly, the most elevated thermal resistance was detected for samples filled with cellulose altered only with solvents (both ethanol and hexane). In order to support the supposed thermal resistance trends of prepared blend materials, apparent activation energies assigned to cellulose degradation (EA1) and polymer matrix decomposition (EA2) have been calculated and presented in the article. It may be evidenced that apparent activation energies assigned to the first decomposition step are higher in case of the systems filled with UFC100 dried prior to the modification process. Moreover, the results have been enriched using surface free energy analysis of the polymer blends. The surface free energy polar part (Ep) raises considering samples filled with not dried UFC100. On the other hand, when cellulose fibers are dried prior to the modification process, then the blend sample’s dispersive part of surface free energy is increased with respect to that containing unmodified fiber. As polymer blend Ep exhibits higher values reflecting enhanced material degradation potential, the cellulose fibers employment leads to more eco-friendly production and responsible waste management. This is in accordance with the rules of sustainable development.
Effects of Propolis and Phenolic Acids on Triple-Negative Breast Cancer Cell Lines: Potential Involvement of Epigenetic Mechanisms
Authors: Assumpção João Henrique Maia , Takeda Agnes Alessandra Sekijima , Sforcin José Maurício , Rainho Cláudia Aparecida
Published: March 2020

Triple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy. Evidence supports that small molecules showing DNA methyltransferase inhibitory activity (DNMTi) are important to sensitize cancer cells to cytotoxic agents, in part, by reverting the acquired epigenetic changes associated with the resistance to therapy. The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs (epi-drugs). We selected three phenolic acids (caffeic, dihydrocinnamic, and p-coumaric) commonly detected in propolis and the (−)-epigallocatechin-3-gallate (EGCG) from green tea, which is a well-known DNA demethylating agent, for further analysis. The treatment with p-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor S-Adenosyl-l-homocysteine (SAH). Although the ethanolic extract of propolis (EEP) did not change the global DNA methylation content, by using MS-PCR (Methylation-Specific Polymerase Chain Reaction) we demonstrated that EEP and EGCG were able to partly demethylate the promoter region of RASSF1A in BT-549 cells. Also, in vitro treatment with EEP altered the RASSF1 protein expression levels. Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressor RASSF1A. These findings suggest that propolis are a promising source for epi-drugs discovery.
Enhancing the Immune Response of a Nicotine Vaccine with Synthetic Small “Non-Natural” Peptides
Authors: Le Hoang-Thanh , Fraleigh Nya L. , Lewicky Jordan D. , Boudreau Justin , Dolinar Paul , Bhardwaj Nitin , Diaz-Mitoma Francisco , Montaut Sabine , Fallahi Sarah , Martel Alexandrine L.
Published: March 2020

The addictive nature of nicotine is likely the most significant reason for the continued prevalence of tobacco smoking despite the widespread reports of its negative health effects. Nicotine vaccines are an alternative to the currently available smoking cessation treatments, which have limited efficacy. However, the nicotine hapten is non-immunogenic, and successful vaccine formulations to treat nicotine addiction require both effective adjuvants and delivery systems. The immunomodulatory properties of short, non-natural peptide sequences not found in human systems and their ability to improve vaccine efficacy continue to be reported. The aim of this study was to determine if small “non-natural peptides,” as part of a conjugate nicotine vaccine, could improve immune responses. Four peptides were synthesized via solid phase methodology, purified, and characterized. Ex vivo plasma stability studies using RP-HPLC confirmed that the peptides were not subject to proteolytic degradation. The peptides were formulated into conjugate nicotine vaccine candidates along with a bacterial derived adjuvant vaccine delivery system and chitosan as a stabilizing compound. Formulations were tested in vitro in a dendritic cell line to determine the combination that would elicit the greatest 1L-1β response using ELISAs. Three of the peptides were able to enhance the cytokine response above that induced by the adjuvant delivery system alone. In vivo vaccination studies in BALB/c mice demonstrated that the best immune response, as measured by nicotine-specific antibody levels, was elicited from the conjugate vaccine structure, which included the peptide, as well as the other components. Isotype analyses highlighted that the peptide was able to shift immune response toward being more humorally dominant. Overall, the results have implications for the use of non-natural peptides as adjuvants not only for the development of a nicotine vaccine but also for use with other addictive substances and conventional vaccination targets as well.
Recent Bio-Advances in Metal-Organic Frameworks
Authors: Tibbetts Isobel , Kostakis George
Published: March 2020

Metal-organic frameworks (MOFs) have found uses in adsorption, catalysis, gas storage and other industrial applications. Metal Biomolecule Frameworks (bioMOFs) represent an overlap between inorganic, material and medicinal sciences, utilising the porous frameworks for biologically relevant purposes. This review details advances in bioMOFs, looking at the synthesis, properties and applications of both bioinspired materials and MOFs used for bioapplications, such as drug delivery, imaging and catalysis, with a focus on examples from the last five years.
Crosslinked Nanocomposite Sodium Alginate-Based Membranes with Titanium Dioxide for the Dehydration of Isopropanol by Pervaporation
Authors: Premakshi H.G. , Kariduraganavar Mahadevappa Y. , Mitchell Geoffrey R.
Published: March 2020

Sodium alginate (NaAlg) based membranes were prepared using a solution technique, crosslinked with poly(styrene sulfonic acid-co-maleic acid) (PSSA-co-MA). Subsequently, the membranes were modified by the incorporation of 0, 10, 20, 30 and 40% w/w of titanium dioxide with respect to sodium alginate. The membranes thus obtained were designated as M, M-1, M-2, M-3 and M-4, respectively. An equilibrium swelling experiment was performed using different compositions of the water and isopropanol mixtures. Subsequently, we used a pervaporation cell fitted with each membrane in order to evaluate the extent of the pervaporation dehydration of isopropanol. Among the membranes studied, the membranes containing 40 mass% of titanium dioxide exhibited the highest separation factor(α) of 24,092, with a flux(J) of 18.61 × 10−2 kg/m2∙h at 30 °C for 10 mass% w/w of water in the feed. The total flux and the flux of water were found to overlap with each other, indicating that these membranes can be effectively used to break the azeotropic point of water–isopropanol mixtures. The results clearly indicate that these nanocomposite membranes exhibit an excellent performance in the dehydration of isopropanol. The activation energy values obtained for the water permeation were significantly lower than those of the isopropanol permeation, underlining that these membranes have a high separation ability for the water–isopropanol system. The estimated activation energies for total permeation (EP) and total diffusion (ED) values ranged between 10.60 kJ∙mol−1 and 3.96 kJ∙mol−1, and 10.76 kJ∙mol−1 and 4.29 kJ∙mol−1, respectively. The negative change in the enthalpy values for all the membranes indicates that sorption was mainly dominated by Langmuir’s mode of sorption.
Treatment with Subcritical Water-Hydrolyzed Citrus Pectin Ameliorated Cyclophosphamide-Induced Immunosuppression and Modulated Gut Microbiota Composition in ICR Mice
Authors: Chen Jianbing , Zhang Chengcheng , Xia Qile , Liu Daqun , Tan Xinghe , Li Yingdi , Cao Yan
Published: March 2020

Subcritical water can effectively hydrolyze pectin into smaller molecules while still maintaining its functional regions. Pectic heteropolysaccharide can mediate immune regulation; however, the possible effects of subcritical water-hydrolyzed citrus pectin (SCP) on the immune response remain unclear. Therefore, the effects of SCP on immunomodulatory functions and intestinal microbial dysbiosis were investigated using a cyclophosphamide-induced immunosuppressed mouse model. In this research, immunosuppressed ICR mice were administrated with SCP at dosages of 300/600/1200 mg/kg.bw by oral gavage, and body weight, immune organ indexes, cytokines, and gut microbiota were determined. The results showed that subcritical water treatment decreased the molecular mass and increased the content of galacturonic acid in citrus pectin hydrolysates. Meanwhile, the treatment with SCP improved immunoregulatory functional properties and bioactivities over the original citrus pectin. For example, SCP protected immune organs (accelerated recovery of immune organ indexes) and significantly enhanced the expression of immune-related cytokines (IL-2, IL-6, IFN-γ, and TNF-α). The results of the 16S rDNA sequencing analysis on an IlluminaMiSeq platform showed that SCP normalized Cy-induced gut dysbiosis. SCP ameliorated Cy-dependent changes in the relative abundance of several taxa, shifting the balance back to normal status (e.g., SCP increased beneficial Muribaculaceae, Ruminococcaceae, Bacteroidaceae, and Prevotellaceae while decreasing pathogenic Brevundimonas and Streptococcus). The results of this study suggest an innovative application of citrus pectin as an immunomodulator.
PETRA: Drug Engineering via Rigidity Analysis
Authors: Herr Sam , Myers-Dean Josh , Read Hunter , Jagodzinski Filip
Published: March 2020

Rational drug design aims to develop pharmaceutical agents that impart maximal therapeutic benefits via their interaction with their intended biological targets. In the past several decades, advances in computational tools that inform wet-lab techniques have aided the development of a wide variety of new medicines with high efficacies. Nonetheless, drug development remains a time and cost intensive process. In this work, we have developed a computational pipeline for assessing how individual atoms contribute to a ligand’s effect on the structural stability of a biological target. Our approach takes as input a protein-ligand resolved PDB structure file and systematically generates all possible ligand variants. We assess how the atomic-level edits to the ligand alter the drug’s effect via a graph theoretic rigidity analysis approach. We demonstrate, via four case studies of common drugs, the utility of our pipeline and corroborate our analyses with known biophysical properties of the medicines, as reported in the literature.
Psoralen Derivatives as Inhibitors of Mycobacterium tuberculosis Proteasome
Authors: Rožman Kaja , Alexander Evan M. , Ogorevc Eva , Bozovičar Krištof , Sosič Izidor , Aldrich Courtney C. , Gobec Stanislav
Published: March 2020

Protein degradation is a fundamental process in all living organisms. An important part of this system is a multisubunit, barrel-shaped protease complex called the proteasome. This enzyme is directly responsible for the proteolysis of ubiquitin- or pup-tagged proteins to smaller peptides. In this study, we present a series of 92 psoralen derivatives, of which 15 displayed inhibitory potency against the Mycobacterium tuberculosis proteasome in low micromolar concentrations. The best inhibitors, i.e., 8, 11, 13 and 15, exhibited a mixed type of inhibition and overall good inhibitory potency in biochemical assays. N-(cyanomethyl)acetamide 8 (Ki = 5.6 µM) and carboxaldehyde-based derivative 15 (Ki = 14.9 µM) were shown to be reversible inhibitors of the enzyme. On the other hand, pyrrolidine-2,5-dione esters 11 and 13 irreversibly inhibited the enzyme with Ki values of 4.2 µM and 1.1 µM, respectively. In addition, we showed that an established immunoproteasome inhibitor, PR-957, is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 ± 1.9 µM, kinact/Ki = 96 ± 41 M−1·s−1). These compounds represent interesting hit compounds for further optimization in the development of new drugs for the treatment of tuberculosis.
Multicomponent Domino Reaction in the Asymmetric Synthesis of Cyclopentan[c]pyran Core of Iridoid Natural Products
Authors: Manchado Alejandro , Ramos Victoria Elena , Díez David , Garrido Narciso M.
Published: March 2020

The asymmetric synthesis of a compound with the cyclopentan[c]pyran core of iridoid natural products in four steps and 40% overall yield is reported. Our methodology includes a one-pot tandem domino reaction which provides a trisubstituted cyclopentane with five new completely determined stereocenters, which were determined through 2D homo and heteronuclear NMR and n.O.e. experiments on different compounds specially designed for this purpose, such as a dioxane obtained from a diol. Due to their pharmaceutical properties, including sedative, analgesic, anti-inflammatory, CNS depressor or anti-conceptive effects, this methodology to produce the abovementioned iridoid derivatives, is an interesting strategy in terms of new drug discovery as well as pharmaceutical development.
Barrier Properties and Characterizations of Poly(lactic Acid)/ZnO Nanocomposites
Authors: Tang Zhenya , Fan Fangling , Chu Zhuangzhuang , Fan Chunli , Qin Yuyue
Published: March 2020

This study aimed to reinforce the barrier performance (i.e., oxygen–gas and water–vapor permeability) of poly(lactic acid) (PLA)-based films. Acetyltributylcitrate and zinc oxide nanoparticle (nano-ZnO), serving as plasticizer and nanofiller, respectively, were blended into a PLA matrix through a solvent-volatilizing method. The structural, morphological, thermal, and mechanical performances were then studied. Scanning electron microscopic images showed a significant dispersion of nano-ZnO in PLA ternary systems with low nano-ZnO content. The interaction between PLA matrix and ZnO nanoparticles was further analyzed by Fourier-transform infrared spectroscopy. Wide-angle X-ray scattering spectroscopy demonstrated high compatibility between PLA matrix and ZnO nanoparticles. Mechanical property studies revealed good tensile strength and low flexibility. Differential scanning calorimetry curves proved that an amorphous structure mostly existed in PLA ternary systems. The improvements in barrier property and tensile strength indicated that the PLA/nano-ZnO composite films could be used for food packaging application.
Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin
Authors: Sato Hideyuki , Tabata Aiko , Moritani Tatsuru , Morinaga Tadahiko , Mizumoto Takahiro , Seto Yoshiki , Onoue Satomi
Published: March 2020

The present study aimed to develop inhalable poly (lactic-co-glycolic acid) (PLGA)-based microparticles of salmon calcitonin (sCT) for sustained pharmacological action by the fine droplet drying (FDD) process, a novel powderization technique employing printing technologies. PLGA was selected as a biodegradable carrier polymer for sustained-release particles of sCT (sCT/SR), and physicochemical characterizations of sCT/SR were conducted. To estimate the in vivo efficacy of the sCT/SR respirable powder (sCT/SR-RP), plasma calcium levels were measured after intratracheal administration in rats. The particle size of sCT/SR was 3.6 µm, and the SPAN factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.65. In the evaluation of the conformational structure of sCT, no significant changes were observed in sCT/SR even after the FDD process. The drug release from sCT/SR showed a biphasic pattern with an initial burst and slow diffusion in simulated lung fluid. sCT/SR-RP showed fine inhalation performance, as evidenced by a fine particle fraction value of 28% in the cascade impactor analysis. After the insufflation of sCT samples (40 µg-sCT/kg) in rats, sCT/SR-RP could enhance and prolong the hypocalcemic action of sCT possibly due to the sustained release and pulmonary absorption of sCT. From these observations, the strategic application of the FDD process could be efficacious to provide PLGA-based inhalable formulations of sCT, as well as other therapeutic peptides, to enhance their biopharmaceutical potentials.
Removal of Tetracycline in Sewage and Dairy Products with High-Stable MOF
Authors: Li Kan , Li Jing-jing , Zhao Ni , Ma Ying , Di Bin
Published: March 2020

Serious environmental and human health problems caused by the abuse of antibiotics have attracted worldwide concern. Recently, metal–organic frameworks (MOFs) with high porosity have drawn wide attention for their effects in the adsorption and removal of pollutants from complex matrices. Herein, a high-stable metal organic framework (MOF), i.e., ((ZnCl2)3(L)2·DMF)n, where L=1,3,5-tris((pyridin-4-ylthio)methyl)benzene), MOF 1, was applied to adsorb and remove tetracycline from sewage and dairy products. The results showed that MOF 1 exhibited a strong performance in the adsorption of tetracycline. The effects of initial pH values, adsorbent dose, contact time and ionic strength of the adsorption performance of MOF 1 were investigated. The adsorption kinetics best fit the pseudo-second order model, and the adsorption isotherms matched the Langmuir adsorption model well. It was indicated that both chemical adsorption and physical adsorption play an important role in the adsorption process, and the adsorption of tetracycline was homogeneous and occurred on a monolayer on the surface of MOF 1. Additionally, the stability of MOF 1 and the details of the adsorption mechanism were also investigated. Thus, this study provides a new candidate for the application of MOFs-based adsorbents in the removal of antibiotics from sewage and dairy products.
C-Terminal 1-Aminoethyltetrazole-Containing Oligopeptides as Novel Alanine Racemase Inhibitors
Authors: Kondacs Laszlo A. , Orenga Sylvain , Anderson Rosaleen J. , Marrs Emma C.L. , Perry John D. , Gray Mark
Published: March 2020

In clinical culture media inoculated with patient samples, selective inhibition of commensal bacteria is essential for accurate diagnosis and effective treatment, as they can mask the presence of pathogenic bacteria. The alanine analogue, 1-aminoethyltetrazole was investigated as a potential alanine racemase inhibitor. For effective uptake and enhanced and selective antibacterial activity, a library of C-terminal 1-aminoethyltetrazole containing di- and oligopeptides were synthesized by solid phase peptide coupling techniques. The investigation of the antimicrobial activity of the synthesised compounds identified several clinically applicable selective inhibitors. These enabled differentiation between the closely related bacteria, Salmonella and Escherichia coli, which can be difficult to discriminate between in a clinical setting. In addition, differentiation between enterococci and other Gram-positive cocci was also seen.
Uncovering Effects from the Structure of Metabarcode Sequences for Metagenetic and Microbiome Analysis
Authors: Molik David C. , Pfrender Michael E. , Emrich Scott J.
Published: March 2020

The advent of next-generation sequencing has allowed for higher-throughput determination of which species live within a specific location. Here we establish that three analysis methods for estimating diversity within samples—namely, Operational Taxonomic Units; the newer Amplicon Sequence Variants; and a method commonly found in sequence analysis, minhash—are affected by various properties of these sequence data. Using simulations we show that the presence of Single Nucleotide Polymorphisms and the depth of coverage from each species affect the correlations between these approaches. Through this analysis, we provide insights which would affect the decisions on the application of each method. Specifically, the presence of sequence read errors and variability in sequence read coverage deferentially affects these processing methods.
Endemic Plant Species Conservation: Biotechnological Approaches
Authors: Coelho Natacha , Gonçalves Sandra , Romano Anabela
Published: March 2020

Endemic plant species are usually more vulnerable to anthropogenic threats and natural changes and, therefore, hold a higher extinction risk. The preservation of these species is a major concern on a worldwide context and in situ protection alone will not guarantee their conservation. Ex situ conservation measures must be undertaken to support the conservation of these species, and seed banking is the more efficient and cost-effective method. However, when seed banking is not an option, alternative approaches should be considered. Biotechnological tools provide new and complementary options for plant conservation including short-, medium-, and long-term strategies, and their application for plant species conservation has increased considerably in the last years. This review provides information about the status of the use biotechnology-based techniques for the conservation of endemic plant species. Particular attention is given to cryopreservation, since is the only long-term ex situ conservation strategy that can complement and support the other conservation measures. The cryopreservation of plant genetic resources is, however, more focused on crop or economically important species and few studies are available for endemic plant species. The plant material used, the cryopreservation methods employed, and the assessment of cryogenic effects are reviewed. The reasons to explain the difficulties in cryopreserving these species are discussed and new strategies are proposed to facilitate and increase the interest on this matter. We expect that further studies on the conservation of endemic plant species will increase in a near future, thus contributing to maintain these valuable genetic resources.
Synergistic Effect of NaCl Pretreatment and PVP on Browning Suppression and Callus Induction from Petal Explants of Paeonia Lactiflora Pall. ‘Festival Maxima’
Authors: Cai Xuan , Wei Hao , Liu Chen , Ren Xiuxia , Thi Luc The , Jeong Byoung Ryong
Published: March 2020

Browning is prevalent in tissue cultures of Paeonia lactiflora Pall. (herbaceous peony), and severely affects and restricts the growth and differentiation of the explants. In this study, dipping excised explants in a sodium chloride (NaCl) solution as a pretreatment, adding polyvinyl pyrrolidone (PVP) to the culture medium, storing planted explants at 4 °C for 24 h, and transferring planted explants to a new medium after 24 h were considered as browning-suppression methods in tissue cultures of herbaceous peony ‘Festival Maxima’. The treated petal explants were cultured in a culture room with a 16-hour photoperiod, 25 °C temperature, and 80% relative humidity in darkness for 4 to 8 weeks. The results demonstrated that dipping excised explants in a 0.5 g·L−1 NaCl solution, adding 0.5 g·L−1 PVP to the medium, storing planted explants at 4 °C for 24 h, and transferring planted explants to the same fresh medium after 24 h could effectively inhibit browning. Adding PVP to the medium led to the greatest browning suppression percentage of 95%. Storing planted explants at 4 °C for 24 h reduced the effectiveness of other treatments in suppressing browning. After 8 weeks, dipping excised explants in a NaCl solution resulted in the highest callus induction percentage of 75%, while storing explants at 4 °C for 24 h suppressed callus formation. It was observed in all treatments that decreases in browning was accompanied with higher levels of phenols and lower activities of phenylalanine ammonia-lyase (PAL) and polyphenoloxidase (PPO). Overall, the results suggest that dipping in a NaCl solution was effective in alleviating the browning issues of herbaceous peony tissue cultures, and had positive synergistic effects with PVP on browning suppression and callus induction.
Lost in Translation: Physiological Roles of Stored mRNAs in Seed Germination
Authors: Sano Naoto , Rajjou Loïc , North Helen M.
Published: March 2020

Seeds characteristics such as germination ability, dormancy, and storability/longevity are important traits in agriculture, and various genes have been identified that are involved in its regulation at the transcriptional and post-transcriptional level. A particularity of mature dry seeds is a special mechanism that allows them to accumulate more than 10,000 mRNAs during seed maturation and use them as templates to synthesize proteins during germination. Some of these stored mRNAs are also referred to as long-lived mRNAs because they remain translatable even after seeds have been exposed to long-term stressful conditions. Mature seeds can germinate even in the presence of transcriptional inhibitors, and this ability is acquired in mid-seed development. The type of mRNA that accumulates in seeds is affected by the plant hormone abscisic acid and environmental factors, and most of them accumulate in seeds in the form of monosomes. Release of seed dormancy during after-ripening involves the selective oxidation of stored mRNAs and this prevents translation of proteins that function in the suppression of germination after imbibition. Non-selective oxidation and degradation of stored mRNAs occurs during long-term storage of seeds so that the quality of stored RNAs is linked to the degree of seed deterioration. After seed imbibition, a population of stored mRNAs are selectively loaded into polysomes and the mRNAs, involved in processes such as redox, glycolysis, and protein synthesis, are actively translated for germination.
Grain Yield Response of Corn (Zea mays L.) to Nitrogen Management Practices and Flooding
Authors: Dill Taylor E. , Harrison Steven K. , Culman Steven W. , Lindsey Alexander J.
Published: March 2020

Flooding can reduce corn growth and yield, but nitrogen (N) management practices may alter the degree to which plants are negatively impacted. Damage caused by flooded conditions may also affect the utilization of a post-flood N application to increase yield. The objectives of this study were to evaluate how pre-plant and pre-plant plus post-flood N applications contribute to corn growth and yield following flood conditions and to quantify the partial return of employing different N management strategies in the event of a flood. A field study was conducted in Ohio using four flood durations (FD; 0, 2, 4, or 6 days initiated at V4 to V5) and three N management practices (0 kg N ha−1, 134 kg N ha−1 applied pre-plant, and 134 pre-plant + 67 kg N ha−1 applied post-flooding). Application of 134 kg N ha−1 increased yield compared to 0 kg N ha−1 by 65%, 68%, 43% and 16% for 0 d, 2 d, 4 d, and 6 d FD, respectively; the application of 134 + 67 kg N ha−1 increased grain yield compared to 134 kg N ha−1 by 7%, 27%, 70%, or 55% for 0 d, 2 d, 4 d, or 6 d FD, respectively. Partial return analysis produced similar results to those for grain yield. Results suggest that in regions prone to early-season flooding, additional N applied post-flood can improve yield and partial return compared to the application of pre-plant alone at a lower rate or no N. Results indicate that total soil nitrate-N levels two weeks after flood initiation may serve as a good predictor of yield.
SQUAMOSA Promoter Binding Protein-Like (SPL) Gene Family: TRANSCRIPTOME-Wide Identification, Phylogenetic Relationship, Expression Patterns and Network Interaction Analysis in Panax ginseng C. A. Meyer
Authors: Li Shaokun , Li Li , Jiang Yang , Wu Jun , Sun Honghua , Zhao Mingzhu , Jiang Yue , Zhu Lei , Wang Yanfang , Su Yingjie , Wang Kangyu , Wang Yi , Zhang Meiping
Published: March 2020

SPL (SQUAMOSA promoter binding protein-like) gene family is specific transcription factor in the plant that have an important function for plant growth and development. Although the SPL gene family has been widely studied and reported in many various plant species from gymnosperm to angiosperm, there are no systematic studies and reports about the SPL gene family in Panax ginseng C. A. Meyer. In this study, we conducted transcriptome-wide identification, evolutionary analysis, structure analysis, and expression characteristics analysis of SPL gene family in Panax ginseng by bioinformatics. We annotated the PgSPL gene family and found that they might involve in multiple functions including encoding structural proteins, but the main function were still focused on the binding function. The result showed that 106 PgSPL transcripts were classified into two clades - A and B, both of which respectively consisted of three groups. Besides, we profiled PgSPL transcripts’ genotypic, temporal, and spatial expression characteristics. Furthermore, we calculated the correlation of PgSPL transcripts in the 14 tissues of a 4 years old ginseng and 42 farmers’ cultivars farmers’ cultivars of 4 years old ginsengs’ roots with both results showing that SPL transcripts formed a single network, which indicated that PgSPLs inter-coordinated when performing their functions. What’s more, we found that most PgSPL transcripts tended to express in older ginseng instead of younger ginseng, which was not only reflected in the expression of more types of SPL transcripts in older ginseng, but also in the higher expression of SPL transcripts in older ginseng. Additionally, we found that four PgSPL transcripts were only massively expressed in roots. According to PgSPL transcripts’ expression characteristics, we found that PgSPL23-35 and PgSPL24-09 were most proper two transcripts to further study as ginseng age’s molecular marker. These results provide the basis for further elucidation of the PgSPL transcripts’ biological function in ginseng and ginseng genetics improvement and gene breeding in the future.
Dynamic of Phenolic Compounds, Antioxidant Activity, and Yield of Rhubarb under Chemical, Organic and Biological Fertilization
Authors: Cojocaru Alexandru , Vlase Laurian , Munteanu Neculai , Stan Teodor , Teliban Gabriel Ciprian , Burducea Marian , Stoleru Vasile
Published: March 2020

In recent years, rhubarb is being increasingly cultivated, as it provides early yields when the vegetables supply to market is deficient and shows high levels of both polyphenols content and antioxidant capacity in edible parts. In 2017, we investigated crops of the rhubarb cultivar Victoria to the fifth year of production. Comparisons were performed between three root phase fertilizations—chemical (NPK 16-16-16®), organic (Orgevit®), and biological (Micoseeds MB®)—plus an unfertilized control. The determinations of polyphenols, the antioxidant capacity, and the yield indicators from the stalks (petioles) of rhubarb were made at each out of the 10 harvests carried out. The highest yield (59.16 t·ha−1) was recorded under the chemical fertilization. The total polyphenols content and antioxidant capacity varied widely from 533.86 mg GAE·g−1 d.w. and 136.86 mmol Trolox·g−1 d.w., respectively in the unfertilized control at the last harvest, up to 3966.56 mg GAE·g−1 d.w. and 1953.97 mmol Trolox·g−1 d.w. respectively under the organic fertilization at the four harvest. From the results of our investigation, it can be inferred that the chemical fertilization was the most effective in terms of yield, whereas the sustainable nutritional management based on organic fertilizer supply led to higher antioxidant compounds and activity.