bluuebunny/crossref_metadata_2025 huggingface dataset:
Listeriosis Outbreak in South Africa: A Comparative Analysis with Previously Reported Cases Worldwide
Authors: Kaptchouang Tchatchouang Christ-Donald , Fri Justine , De Santi Mauro , Brandi Giorgio , Schiavano Giuditta Fiorella , Amagliani Giulia , Ateba Collins Njie
Published: January 2020

Listeria species are Gram-positive, rod-shaped, facultative anaerobic bacteria, which do not produce endospores. The genus, Listeria, currently comprises 17 characterised species of which only two (L. monocytogenes and L. ivanovii) are known to be pathogenic to humans. Food products and related processing environments are commonly contaminated with pathogenic species. Outbreaks and sporadic cases of human infections resulted in considerable economic loss. South Africa witnessed the world’s largest listeriosis outbreak, characterised by a progressive increase in cases of the disease from January 2017 to July 2018. Of the 1060 laboratory-confirmed cases of listeriosis reported by the National Institute of Communicable Diseases (NICD), 216 deaths were recorded. Epidemiological investigations indicated that ready-to-eat processed meat products from a food production facility contaminated with L. monocytogenes was responsible for the outbreak. Multilocus sequence typing (MLST) revealed that a large proportion (91%) of the isolates from patients were sequence type 6 (ST6). Recent studies revealed a recurrent occurrence of small outbreaks of listeriosis with more severe side-effects in humans. This review provides a comparative analysis of a recently reported and most severe outbreak of listeriosis in South Africa, with those previously encountered in other countries worldwide. The review focuses on the transmission of the pathogen, clinical symptoms of the disease and its pathogenicity. The review also focuses on the major outbreaks of listeriosis reported in different parts of the world, sources of contamination, morbidity, and mortality rates as well as cost implications. Based on data generated during the outbreak of the disease in South Africa, listeriosis was added to the South African list of mandatory notifiable medical conditions. Surveillance systems were strengthened in the South African food chain in order to assist in preventing and facilitating early detection of both sporadic cases and outbreaks of infections caused by these pathogens in humans.
Algal Lipids as Biocollector for Recovery of Coal from Fine Coal Waste by Froth Flotation
Authors: Chiodza Kudzai G. , Harrison Susan T. L. , Fagan-Endres Marijke A.
Published: January 2020

Raw algal lipids (RALs) and their derivatives (fatty acid methyl esters; FAMEs) were investigated as biocollectors for the recovery of coal from ash-rich fine coal waste by froth flotation. Testing was done on fine coal discards from two South African sites—a high ash (50%), high sulphur (5.7%) sample and a lower ash (26%), low sulphur (0.91%) sample. The yield and recovery of combustibles on using biocollectors was similar to, or better than, with oleic acid, a polar collector demonstrated as a good collector in previous research. The RALs and FAMEs reduced the ash and sulphur content of the combustible fraction of the high ash-high sulphur sample to between 23–28% and 1.9–3.3%, respectively. The chemical modification of RALs to FAMEs provided potential for improving the selectivity of the recovery of combustibles. It also resulted in a change of the optimum operating pH, with RALs yielding better results at the natural pH of the sample (pH 2.7), while FAMEs performed best at pH 7.
Efficient and Stable Magnetic Chitosan-Lipase B from Candida Antarctica Bioconjugates in the Enzymatic Kinetic Resolution of Racemic Heteroarylethanols
Authors: Spelmezan Cristina Georgiana , Bencze László Csaba , Katona Gabriel , Irimie Florin Dan , Paizs Csaba , Toșa Monica Ioana
Published: January 2020

Lipase B from Candida antarctica immobilized by covalent binding on sebacoyl-activated chitosan-coated magnetic nanoparticles proved to be an efficient biocatalyst (49.2–50% conversion in 3–16 h and >96% enantiomeric excess) for the enzymatic kinetic resolution of some racemic heteroarylethanols through transesterification with vinyl acetate. Under optimal conditions (vinyl acetate, n-hexane, 45 °C), the biocatalyst remains active after 10 cycles.
Effects of Orange Extracts on Longevity, Healthspan, and Stress Resistance in Caenorhabditis elegans
Authors: Wang Jing , Deng Na , Wang Hong , Li Tong , Chen Ling , Zheng Bisheng , Liu Rui Hai
Published: January 2020

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan.
The Effects of Ultraviolet A/B Treatments on Anthocyanin Accumulation and Gene Expression in Dark-Purple Tea Cultivar ‘Ziyan’ (Camellia sinensis)
Authors: Li Wei , Tan Liqiang , Zou Yao , Tan Xiaoqin , Huang Jiacheng , Chen Wei , Tang Qian
Published: January 2020

‘Ziyan’ is a novel anthocyanin-rich tea cultivar with dark purple young shoots. However, how its anthocyanin accumulation is affected by environmental factors, such as ultraviolet (UV), remains unclear. In this study, we observed that UV light treatments stimulated anthocyanin accumulation in ‘Ziyan’ leaves, and we further analyzed the underlying mechanisms at gene expression and enzyme activity levels. In addition, the catechins and chlorophyll contents of young shoots under different light treatments were also changed. The results showed that the contents of total anthocyanins and three major anthocyanin molecules, i.e., delphinidin, cyanidin, and pelargonidin, were significantly higher in leaves under UV-A, UV-B, and UV-AB treatments than those under white light treatment alone. However, the total catechins and chlorophyll contents in these purple tea plant leaves displayed the opposite trends. The anthocyanin content was the highest under UV-A treatment, which was higher by about 66% than control. Compared with the white light treatment alone, the enzyme activities of chalcone synthase (CHS), flavonoid 3′,5′-hydroxylase (F3′5′H), and anthocyanidin synthase (ANS) under UV treatments increased significantly, whereas the leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR) activities reduced. There was no significant difference in dihydroflavonol 4-reductase (DFR) activity under all treatments. Comparative transcriptome analyses unveiled that there were 565 differentially expressed genes (DEGs) of 29,648 genes in three pair-wise comparisons (white light versus UV-A, W vs. UV-A; white light versus UV-B, W vs. UV-A; white light versus UV-AB, W vs. UV-AB). The structural genes in anthocyanin pathway such as flavanone 3-hydroxylase (F3H), F3′5′H, DFR, and ANS, and regulatory gene TT8 were upregulated under UV-A treatment; F3′5′H, DFR, ANS, and UFGT and regulatory genes EGL1 and TT2 were upregulated under UV-AB treatment. However, most structural genes involved in phenylpropanoid and flavonoid pathways were downregulated under UV-B treatment compared with control. The expression of LAR and ANR were repressed in all UV treatments. Our results indicated that UV-A and UV-B radiations can induce anthocyanin accumulation in tea plant ‘Ziyan’ by upregulating the structural and regulatory genes involved in anthocyanin biosynthesis. In addition, UV radiation repressed the expression levels of LAR, ANR, and FLS, resulting in reduced ANR activity and a metabolic flux shift toward anthocyanin biosynthesis.
Systematic Detection and Identification of Bioactive Ingredients from Citrus aurantium L. var. amara Using HPLC-Q-TOF-MS Combined with a Screening Method
Authors: Yu Liuyi , Chen Miaofen , Liu Jinghong , Huang Xiuqiong , He Wei , Qing Zhixing , Zeng Jianguo
Published: January 2020

Bitter orange, Citrus aurantium L. var. amara (CAVA), is an important crop and its flowers and fruits are widely used in China as a food spice, as well as in traditional Chinese medicine, due to its health-promoting properties. The secondary metabolites that are present in plant-derived foods or medicines are, in part, responsible for the health benefits and desirable flavor profiles. Nevertheless, detailed information about the bioactive ingredients in CAVA is scarce. Therefore, this study was aimed at exploring the phytochemicals of CAVA by high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Here, a systematic screening method combined with HPLC-Q-TOF-MS was presented. This technique was used to systematically screen metabolites, primarily from the complex matrix of CAVA, and to identify these compounds by their exact masses, characteristic fragment ions, and fragmentation behaviors. A total of 295 metabolites were screened by the screening method and 89 phytochemicals were identified in the flowers, fruits, roots, leaves, and branches of CAVA. For the first time, 69 phytochemicals (flavonoids, alkaloids, terpenoids, etc.) were reported from CAVA. The results highlight the importance of CAVA as a source of secondary metabolites in the food, medicine, and nutraceutical industries.
Correlations Between Trace Elements in Selected Locations of the Human Brain in Individuals with Alcohol Use Disorder
Authors: Grochowski Cezary , Szukała Magdalena , Litak Jakub , Budny Agnieszka , Proch Jędrzej , Majerek Dariusz , Blicharska Eliza , Niedzielski Przemysław
Published: January 2020

Trace element distribution varies in different locations of the human brain. Several elements were found to cause various negative effects, such as neurodegeneration. In this paper, we analyzed the interactions between seven trace elements: zinc (Zn), selenium (Se), manganese (Mg), iron (Fe), copper (Cu), chromium (Cr) and cobalt (Co) in individuals with alcohol use disorder (AUD) and individuals without (control group). Brain tissue samples from 31 individuals with AUD and 31 control subjects were harvested. Inductively coupled plasma optical emission spectrometry was used for trace element determination. In the control group, there were several positive correlations between Cr, Cu, Fe and Mn. In the AUD group, positive correlations between Co and Cr, Cu, Fe, Mn, Zn were found. The majority of correlations between Zn and other elements are positive. In the studied group, Mn had strong positive correlations with Co, Cr, Cu and Fe. The strongest positive correlation found between average element concentration was between Cu and Cr. The knowledge of kinetics and metabolism of trace elements as well as the impact of alcohol on these processes is essential for understanding the pathological processes and functioning of human brain tissue.
New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation
Authors: Chen Guanglin , Jiang Ziran , Zhang Qiang , Wang Guangdi , Chen Qiao-Hong
Published: January 2020

Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to β-tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability. More importantly, conversion of its chemically fragile side chain into a stabilized bioisostere is envisioned to enable zampanolide to possess more drug-like properties. As part of our ongoing project aiming to develop its mimics with a stable side chain using straightforward synthetic approaches, 2-fluorobenzyl alcohol was designed as a bioisosteric surrogate for the side chain based on its binding conformation as confirmed by the X-ray structure of tubulin complexed with zampanolide. Two new zampanolide mimics with the newly designed side chain have been successfully synthesized through a 25-step chemical transformation for each. Yamaguchi esterification and intramolecular Horner–Wadsworth–Emmons condensation were used as key reactions to construct the lactone core. The chiral centers at C17 and C18 were introduced by the Sharpless asymmetric dihydroxylation. Our WST-1 cell proliferation assay data in both docetaxel-resistant and docetaxel-naive prostate cancer cell lines revealed that compound 6 is the optimal mimic and the newly designed side chain can serve as a bioisostere for the chemically fragile N-acetyl hemiaminal side chain in zampanolide.
A Recyclable, Metal-Free Mechanochemical Approach for the Oxidation of Alcohols to Carboxylic Acids
Authors: Denlinger Kendra Leahy , Carr Preston , Waddell Daniel C. , Mack James
Published: January 2020

The oxidation of primary alcohols under mechanochemical conditions in a Spex8000M Mixer/Mill was investigated. To facilitate ease of separation and recyclability, a polystyrene-bound version of a TEMPO catalyst was employed. When paired with Oxone® in a stainless-steel vial with a stainless-steel ball, several primary alcohols were successfully oxidized to the corresponding carboxylic acids. The product was isolated using gravity filtration, which also allowed for the polystyrene-bound TEMPO catalyst to be recovered and reused in subsequent oxidation reactions. Furthermore, it was demonstrated that the size and steric hindrance of the primary alcohol does not hinder the rate of the reaction. Finally, the aldehyde was selectively obtained from a primary alcohol under ball milling conditions by using a combination of non-supported TEMPO with a copper vial and copper ball.
New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells
Authors: Smagurauskaite Gintare , Mahale Jagdish , Brown Karen , Thomas Anne L. , Howells Lynne M.
Published: January 2020

Curcumin has been investigated extensively for cancer prevention, but it has been proposed that long-term treatments may promote clonal evolution and gain of cellular resistance, potentially rendering cancer cells less sensitive to future therapeutic interventions. Here, we used long-term, low-dose treatments to determine the potential for adverse effects in non-small cell lung cancer (NSCLC) cells. IC50s for curcumin, cisplatin, and pemetrexed in A549, PC9, and PC9ER NSCLC cells were evaluated using growth curves. IC50s were subsequently re-assessed following long-term, low-dose curcumin treatment and a three-month treatment withdrawal period, with a concurrent assessment of oncology-related protein expression. Doublet cisplatin/pemetrexed-resistant cell lines were created and the IC50 for curcumin was determined. Organotypic NSCLC-fibroblast co-culture models were used to assess the effects of curcumin on invasive capacity. Following long-term treatment/treatment withdrawal, there was no significant change in IC50s for the chemotherapy drugs, with chemotherapy-resistant cell lines exhibiting similar sensitivity to curcumin as their non-resistant counterparts. Curcumin (0.25–0.5 µM) was able to inhibit the invasion of both native and chemo-resistant NSCLC cells in the organotypic co-culture model. In summary, long-term curcumin treatment in models of NSCLC neither resulted in the acquisition of pro-carcinogenic phenotypes nor caused resistance to chemotherapy agents.
Acrylamide Decreases Cell Viability, and Provides Oxidative Stress, DNA Damage, and Apoptosis in Human Colon Adenocarcinoma Cell Line Caco-2
Authors: Nowak Adriana , Zakłos-Szyda Małgorzata , Żyżelewicz Dorota , Koszucka Agnieszka , Motyl Ilona
Published: January 2020

Acrylamide (AA) toxicity remains an interesting subject in toxicological research. The aim of the research performed in this paper was to determine mechanisms of cyto- and genotoxic effects of AA on the human colon adenocarcinoma cell line Caco-2, to estimate the inhibitory concentration (IC)50 values in cell viability assays, to measure the basal and oxidative DNA damage as well as the oxidative stress leading to apoptosis, and to assess the morphological changes in cells using microscopic methods. It has been proven that AA induces cytotoxic and genotoxic effects on Caco-2 cells. Higher cytotoxic activity was gained in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay compared with the PrestoBlue assay, with IC50 values of 5.9 and 8.9 mM after 24 h exposure, respectively. In the single-cell gel electrophoresis assay, the greatest DNA damage was caused by the highest concentration of acrylamide equal to 12.5 mM (89.1% ± 0.9%). AA also induced oxidative DNA damage and generated reactive oxygen species (ROS), which was concentration dependent and correlated with the depletion of mitochondrial membrane potential and apoptosis induction. In the microscopic staining of cells, AA in the dosage close to the IC50 induced morphological changes typical for apoptosis. Taken together, these results demonstrate that AA has a pro-oxidative effect on Caco-2 cells, leading to apoptotic cell death.
Anthocyanin Metabolites in Human Urine after the Intake of New Functional Beverages
Authors: Agulló Vicente , Villaño Débora , García-Viguera Cristina , Domínguez-Perles Raúl
Published: January 2020

Sugar intake abuse is directly related with the increase of metabolic diseases such as type 2 diabetes, obesity, and insulin resistance. Along this line, the development of new beverages using alternative sweeteners could help with combatting the pathophysiological disorders associated to the consumption of sugar. To provide evidence on this issue, in the present work, the bioavailability of anthocyanins was evaluated after the acute ingestion of a new maqui-citrus-based functional beverage rich in polyphenols, and supplemented with a range of sweeteners including sucrose (natural high caloric), stevia (natural non-caloric), and sucralose (artificial non-caloric), as an approach that would allow reducing the intake of sugars while providing bioactive phenolic compounds (anthocyanins). This approach allowed the evaluation of the maximum absorption and the diversity of metabolites excreted through urine. The beverages created were ingested by volunteers (n = 20) and the resulting anthocyanin metabolites in their urine were analyzed by UHPLC-ESI-MS/MS. A total of 29 degradation metabolites were detected: Caffeic acid, catechol, 3,4-dihidroxifenilacetic acid, hippuric acid, trans-ferulic acid, 2,4,6-trihydroxybenzaldehyde, trans-isoferulic acid, and vanillic acid derivatives, where peak concentrations were attained at 3.5 h after beverage intake. Sucralose was the sweetener that provided a higher bioavailability for most compounds, followed by stevia. Sucrose did not provide a remarkably higher bioavailability of any compounds in comparison with sucralose or stevia. The results propose two sweetener alternatives (sucralose and stevia) to sucrose, an overused high calorie sweetener that promotes some metabolic diseases.
Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry
Authors: Reddy Priyanka , Elkins Aaron , Hemsworth Joanne , Guthridge Kathryn , Vassiliadis Simone , Read Elizabeth , Spangenberg German , Rochfort Simone
Published: January 2020

Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals.
Performance of Graphite-Dispersed Li2CO3-K2CO3 Molten Salt Nanofluid for a Direct Absorption Solar Collector System
Authors: Karim M. A. , Islam Majedul , Arthur Owen , Yarlagadda Prasad KDV
Published: January 2020

Considered to be the next generation of heat transfer fluids (HTFs), nanofluids have been receiving a growing interest over the past decade. Molten salt nanofluids have been shown to have great potential as an HTF for use in high temperature applications such as direct absorption solar collector (DAC) system. Very few studies using molten salt nanofluids as the HTF in a DAC receiver can be found in the open literature. This study aimed to develop a 3D computational fluid dynamics model of the receiver of a DAC using graphite-nanoparticle-dispersed Li2CO3-K2CO3 molten salt nanofluid to investigate the effects of design and operation parameters on receiver performance. Receiver total efficiency using Li2CO3-K2CO3 salt was compared with that using solar salt nanofluid. Spectral properties of the base fluid and nanoparticles were modeled as wavelength-dependent and the absorption of the solar radiation was modeled as a volumetric heat release in the flowing heat transfer fluid. Initial results show that the receiver efficiency increases with increasing solar concentration, decreasing nanoparticle volume fraction, and decreasing receiver length. It was also found that the Carnot efficiency increases with increasing receiver length and nanoparticle volume fraction, and decreasing solar concentration and inlet velocity. Comparative study shows that solar salt HTF could provide higher total efficiency. However, a higher operating temperature of Li2CO3-K2CO3 will allow for a greater amount of thermal energy storage for a smaller volume of liquid.
Three Novel Zn-Based Coordination Polymers: Synthesis, Structure, and Effective Detection of Al3+ and S2− Ions
Authors: Wang Yuna , Zhang Xiaofeng , Zhao Yanru , Zhang Suoshu , Li Shifen , Jia Lei , Du Lin , Zhao Qihua
Published: January 2020

Three novel Zn-based coordination polymers (CPs), [Zn(MIPA)]n (1), {[Zn(MIPA)(4,4′-bipy)0.5(H2O)]·1.5H2O}n (2), and {[Zn(MIPA)(bpe)]·H2O}n (3) (MIPA = 4-methoxyisophthalic acid, 4,4′-bipy = 4,4′-bipyridine, bpe = (E)-1,2-di(pyridine-4-yl)ethane), were constructed by ligand 4-methoxyisophthalic acid under solvothermal conditions. Compound 1 features a beaded 2D-layer architecture, while compound 2 presents a 2-fold interpenetrating structure with a uninodal three-connected hcb topology. Compound 3 has a 3-fold interpenetrated four-connected dmp topology. Photoluminescence investigations of compound 2 were explored in detail, by which ions were detected, and it was observed to have the highest quenching efficiency toward Al3+ and S2− ions. The possible fluorescence quenching mechanisms of 2 toward Al3+ and S2− ions were also explored. To the best of our knowledge, this is the first potential dual-responsive luminescent probe based on a Zn(II) coordination polymer for detecting Al3+ and S2− ions via a luminescence quenching effect in ethanol.
Control of Growth and Persistence of Listeria monocytogenes and β-Lactam-Resistant Escherichia coli by Thymol in Food Processing Settings
Authors: Cusimano Maria Grazia , Di Stefano Vita , La Giglia Maria , Di Marco Lo Presti Vincenzo , Schillaci Domenico , Pomilio Francesco , Vitale Maria
Published: January 2020

The main objective of this study was to evaluate the efficacy of thymol in controlling environmental contamination in food processing facilities. The effect of thymol was tested as an agent to prevent planktonic and bacterial biofilm growth of twenty-five Listeria monocytogenes isolates from a variety of foods and five Escherichia coli isolates from a farm. The E. coli isolates were positive for extended spectrum β-lactamase (ESBL) genes. All isolates and reference strains were susceptible to thymol at Minimum inhibitory concentration (MIC) values ranging from 250 to 800 μg/mL. An interesting activity of interference with biofilm formation of L. monocytogenes and E. coli was found for thymol at sub-MIC concentrations of 200, 100, 75, and 50 μg/mL. Anti-biofilm activity ranging from 59.71% to 66.90% against pre-formed 24-h-old L. monocytogenes biofilms at concentrations of 500 or 800 µg/mL, corresponding to 2× MIC, was determined against free-living forms of six isolates chosen as the best or moderate biofilm producers among the tested strains. The property of thymol to attack L. monocytogenes biofilm formation was also observed at a concentration of 100 µg/mL, corresponding to 1/4 MIC, by using a stainless-steel model to simulate the surfaces in food industries. This study gives information on the use of thymol in food processing setting.
Probabilistic Approach for Virtual Screening Based on Multiple Pharmacophores
Authors: Madzhidov Timur I. , Rakhimbekova Assima , Kutlushuna Alina , Polishchuk Pavel
Published: January 2020

Pharmacophore modeling is usually considered as a special type of virtual screening without probabilistic nature. Correspondence of at least one conformation of a molecule to pharmacophore is considered as evidence of its bioactivity. We show that pharmacophores can be treated as one-class machine learning models, and the probability the reflecting model’s confidence can be assigned to a pharmacophore on the basis of their precision of active compounds identification on a calibration set. Two schemes (Max and Mean) of probability calculation for consensus prediction based on individual pharmacophore models were proposed. Both approaches to some extent correspond to commonly used consensus approaches like the common hit approach or the one based on a logical OR operation uniting hit lists of individual models. Unlike some known approaches, the proposed ones can rank compounds retrieved by multiple models. These approaches were benchmarked on multiple ChEMBL datasets used for ligand-based pharmacophore modeling and externally validated on corresponding DUD-E datasets. The influence of complexity of pharmacophores and their performance on a calibration set on results of virtual screening was analyzed. It was shown that Max and Mean approaches have superior early enrichment to the commonly used approaches. Thus, a well-performing, easy-to-implement, and probabilistic alternative to existing approaches for pharmacophore-based virtual screening was proposed.
Hf(OTf)4 as a Highly Potent Catalyst for the Synthesis of Mannich Bases under Solvent-Free Conditions
Authors: Han Shuai-Bo , Wei Jing-Ying , Peng Xiao-Chong , Liu Rong , Gong Shan-Shan , Sun Qi
Published: January 2020

Hf(OTf)4 was identified as a highly potent catalyst (0.1–0.5 mol%) for three-component Mannich reaction under solvent-free conditions. Hf(OTf)4-catalyzed Mannich reaction exhibited excellent regioselectivity and diastereoselectivity when alkyl ketones were employed as substrates. 1H NMR tracing of the H/D exchange reaction of ketones in MeOH-d4 indicated that Hf(OTf)4 could significantly promote the keto-enol tautomerization, thereby contributing to the acceleration of reaction rate.
Analysis of Flavonoids in Dalbergia odorifera by Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry
Authors: Zhao Xiangsheng , Zhang Shihui , Liu Dan , Yang Meihua , Wei Jianhe
Published: January 2020

Dalbergia odorifera, a traditional Chinese medicine, has been used to treat cardio- and cerebrovascular diseases in China for thousands of years. Flavonoids are major active compounds in D. odorifera. In this paper, a rapid and sensitive ultra-high performance liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for simultaneous determination of 17 flavonoids in D. odorifera. Quantification was performed by multiple reaction monitoring using electrospray ionization in negative ion mode. Under the optimum conditions, calibration curves for the 17 analytes displayed good linearity (r2 > 0.9980). The intra- and inter-day precisions (relative standard deviations) were lower than 5.0%. The limit of quantitation ranged from 0.256 to 18.840 ng/mL. The mean recovery range at three spiked concentrations was 94.18–101.97%. The validated approach was successfully applied to 18 samples of D. odorifera. Large variation was observed for the contents of the 17 analytes. Sativanone and 3′-O-methylviolanone were the dominant compounds. The fragmentation behaviors of six flavonoids were investigated using UPLC with quadrupole time-of-flight tandem mass spectrometry. In negative ion electrospray ionization mass spectrometry, all the flavonoids yielded prominent [M − H]− ions. Fragments for losses of CH3, CO, and CO2 were observed in the mass spectra. Formononetin, liquiritigenin, isoliquiritigenin, sativanone, and alpinetin underwent retro-Diels–Alder fragmentations. The proposed method will be helpful for quality control of D. odorifera.
Enzymatic Synthesis and Flash Chromatography Separation of 1,3-Diferuloyl-sn-Glycerol and 1-Feruloyl-sn-Glycerol
Authors: Compton David L. , Appell Michael , Kenar James A. , Evans Kervin O.
Published: January 2020

Ethyl ferulate was transesterified with Enova Oil (a soy-based vegetable oil containing 80–85% diacylglycerol) using Novozym 435 at 60 °C. The resultant feruloylated vegetable oil reaction product produced a precipitate (96.4 g, 4.02 wt%) after 7 d of standing at room temperature. Preliminary characterization of the precipitate identified the natural phenylpropenoids 1,3-diferuloyl-sn-glycerol (F2G) and 1-feruloyl-sn-glycerol (FG) as the major components. A flash chromatography method was developed and optimized (e.g., mass of sample load, flow rate, binary solvent gradient slope, and separation run length) using a binary gradient of hexane and acetone mobile phase and silica gel stationary phase to separate and isolate F2G and FG. The optimized parameters afforded F2G (1.188 ± 0.052 g, 39.6 ± 1.7%) and FG (0.313 ± 0.038 g, 10.4 ± 1.3%) from 3.0 g of the transesterification precipitate, n = 10 trials. Overall, all flash chromatography separations combined, F2G (39.1 g, 40.6%) and FG (9.4 g, 9.8%) were isolated in a combined yield of 48.5 g (51.4%), relative to the 96.4 g of transesterification precipitate collected. The optimized flash chromatography method was a necessary improvement over previously reported preparative HPLC and column chromatography methods used to purify milligram to low gram quantities of F2G and FG to be able to process ~100 g of material in a timely, efficient manner.
Tuning the Mechanical and Adhesion Properties of Carbon Nanotubes Using Aligned Cellulose Wrap (Cellulose Nanotube): A Molecular Dynamics Study
Authors: Shishehbor Mehdi , Pouranian M. Reza
Published: January 2020

Improving the adhesion properties of carbon nanotubes (CNTs) at the molecular scale can significantly enhance dispersion of CNT fibers in polymer matrix and unleash the dormant extraordinary mechanical properties of CNTs in CNT-polymer nanocomposites. Inspired by the outstanding adhesion, dispersion, mechanical, and surface functionalization properties of crystalline nanocellulose (CNC), this paper studies the mechanical and adhesion properties of CNT wrapped by aligned cellulose chains around CNT using molecular dynamic simulations. The strength, elastic modulus, and toughness of CNT-cellulose fiber for different cellulose contents are obtained from tensile and compression tests. Additionally, the effect of adding cellulose on the surface energy, interfacial shear modulus, and strength is evaluated. The result shows that even adding a single layer cellulose wrap (≈55% content) significantly decreases the mechanical properties, however, it also dramatically enhances the adhesion energy, interfacial shear strength, and modulus. Adding more cellulose layers, subsequently, deceases and increases mechanical properties and adhesion properties, respectively. In addition, analysis of nanopapers of pristine CNT, pristine CNC, and CNT-wrapped cellulose reveals that CNT-wrapped cellulose nanopapers are strong, stiff, and tough, while for CNT and CNC either strength or toughness is compromised. This research shows that cellulose wraps provide CNT fibers with tunable mechanical properties and adhesion energy that could yield strong and tough materials due to the excellent mechanical properties of CNT and active surface and hydrogen bonding of cellulose.
Preparation of Nanocomposite Polymer Electrolyte via In Situ Synthesis of SiO2 Nanoparticles in PEO
Authors: Tan Xinjie , Wu Yongmin , Tang Weiping , Song Shufeng , Yao Jianyao , Wen Zhaoyin , Lu Li , Savilov Serguei V. , Hu Ning , Molenda Janina
Published: January 2020

Composite polymer electrolytes provide an emerging solution for new battery development by replacing liquid electrolytes, which are commonly complexes of polyethylene oxide (PEO) with ceramic fillers. However, the agglomeration of fillers and weak interaction restrict their conductivities. By contrast with the prevailing methods of blending preformed ceramic fillers within the polymer matrix, here we proposed an in situ synthesis method of SiO2 nanoparticles in the PEO matrix. In this case, robust chemical interactions between SiO2 nanoparticles, lithium salt and PEO chains were induced by the in situ non-hydrolytic sol gel process. The in situ synthesized nanocomposite polymer electrolyte delivered an impressive ionic conductivity of ~1.1 × 10−4 S cm−1 at 30 °C, which is two orders of magnitude higher than that of the preformed synthesized composite polymer electrolyte. In addition, an extended electrochemical window of up to 5 V vs. Li/Li+ was achieved. The Li/nanocomposite polymer electrolyte/Li symmetric cell demonstrated a stable long-term cycling performance of over 700 h at 0.01–0.1 mA cm−2 without short circuiting. The all-solid-state battery consisting of the nanocomposite polymer electrolyte, Li metal and LiFePO4 provides a discharge capacity of 123.5 mAh g−1, a Coulombic efficiency above 99% and a good capacity retention of 70% after 100 cycles.
Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures
Authors: Igaz Nóra , Szőke Krisztina , Kovács Dávid , Buhala Andrea , Varga Zoltán , Bélteky Péter , Rázga Zsolt , Tiszlavicz László , Vizler Csaba , Hideghéty Katalin , Kónya Zoltán , Kiricsi Mónika
Published: January 2020

Radiosensitizing agents are capable of augmenting the damage of ionizing radiation preferentially on cancer cells, thereby increasing the potency and the specificity of radiotherapy. Metal-based nanoparticles have recently gathered ground in radio-enhancement applications, owing to their exceptional competence in amplifying the cell-killing effects of irradiation. Our aim was to examine the radiosensitizing performance of gold nanoparticles (AuNPs) and the chromatin-modifying histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alone and in combination. We observed that the colony-forming capability of cancer cells decreased significantly and the DNA damage, detected by γH2AX immunostaining, was substantially greater after combinational treatments than upon individual drug exposures followed by irradiation. Synergistic radiosensitizing effects of AuNPs and SAHA were proven on various cell lines, including radioresistant A549 and DU-145 cancer cells. 3D cultures often manifest radio- and drug-resistance, nevertheless, AuNPs in combination with SAHA could effectively enhance the potency of irradiation as the number of viable cells decreased significantly when spheroids received AuNP + SAHA prior to radiotherapy. Our results imply that a relaxed chromatin structure induced by SAHA renders the DNA of cancerous cells more susceptible to the damaging effects of irradiation-triggered, AuNP-released reactive electrons. This feature of AuNPs should be exploited in multimodal treatment approaches.
Surfactant-Free Synthesis of Nb2O5 Nanoparticles Anchored Graphene Nanocomposites with Enhanced Electrochemical Performance for Supercapacitor Electrodes
Authors: Nagaraju P. , Vasudevan R. , Alsalme A. , Alghamdi A. , Arivanandhan M. , Jayavel R.
Published: January 2020

Nb2O5/graphene nanocomposites without any surfactant are synthesized by an in situ microwave irradiation technique. Structural and morphological studies revealed that the prepared composites were composed of Nb2O5 nanoparticles intercalated into the graphene sheet. The thermal stability of graphene oxide, Nb2O5, and Nb2O5/graphene nanocomposite was studied by the TGA. The electrochemical properties are assessed by cyclic voltammetry, chronopotentiometry and electrochemical impedance spectroscopy analyses. The specific capacitance of Nb2O5/graphene nanocomposites is greater (633 Fg−1) than pure Nb2O5 nanoparticles (221 Fg−1) and graphene (290 Fg−1) at a current density of 1 Ag−1. The long-term cyclic measurement confirms higher cyclic stability of the nanocomposite with capacitance retention of 99.3% after 5000 cycles without performance degradation. The composites exhibit higher electrochemical conductivity and allow effective ions and charge transport over the entire electrode surface with aqueous electrolyte. The electrochemical study suggests that Nb2O5/graphene nanocomposites have the potential to be an effective electrode for superior performance supercapacitor applications.
Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma
Authors: Ledezma Debbie K. , Balakrishnan Preethi B. , Cano-Mejia Juliana , Sweeney Elizabeth E. , Hadley Melissa , Bollard Catherine M. , Villagra Alejandro , Fernandes Rohan
Published: January 2020

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.
Preparation and Characterization of Epoxy Resin Filled with Ti3C2Tx MXene Nanosheets with Excellent Electric Conductivity
Authors: Feng Ailing , Hou Tianqi , Jia Zirui , Zhang Yi , Zhang Fan , Wu Guanglei
Published: January 2020

MXene represents new kinds of two-dimensional material transition metal carbides and/or carbonitrides, which have attracted much attention in various applications including electrochemical storage devices, catalysts, and polymer composite. Here, we report a facile method to synthesize Ti3C2Tx MXene nanosheets and prepare a novel electrically conductive adhesive based on epoxy resin filled with Ti3C2Tx MXene nanosheets by solution blending. The structure, morphology, and performance of Ti3C2Tx MXene nanosheets and epoxy/Ti3C2Tx MXene nanosheets composite were investigated. The results show that Ti3C2Tx MXene possesses nanosheet structure. Ti3C2Tx MXene nanosheets were homogeneously dispersed in epoxy resin. Electrical conductivity and mechanical properties measurements reveal that the epoxy/Ti3C2Tx MXene nanosheet composite exhibited both good electrical conductivity (4.52 × 10−4 S/m) and favorable mechanical properties (tensile strength of 66.2 MPa and impact strength of 24.2 kJ/m2) when the content of Ti3C2Tx MXene nanosheets is 1.2 wt %. Thus, Ti3C2Tx MXene is a promising filler for electrically conductive adhesive with high electric conductivity and high mechanical performance.
Structural, Thermal, and Release Properties of Hybrid Materials Based on Layered Zinc Hydroxide and Caffeic Acid
Authors: Ruiz Christhy V. , Becerra María E. , Giraldo Oscar
Published: January 2020

Caffeic acid (CA) molecules were immobilized in a layered inorganic host matrix based on zinc hydroxide structures with different starting interlayer anions, nitrate, and acetate. The chemical composition, structure, thermal stability, morphology, and surface of the host matrices and hybrid compounds were analyzed by X-ray diffraction (XRD), themogravimetric/differencial thermal analysis (TG/DTA), Fourier transform infrarred spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Additionally, the surface charge of the materials was investigated using zeta potential at pH ~7. The results show an influence of the surface charge on the chemical, interaction, and structure of the resulting hybrid materials as a function of the starting layered structures. An expansion of the basal spacing to 10.20 Å for zinc hydroxide nitrate (ZHN), and a shrinkage to 10.37 Å for zinc hydroxide acetate (ZHA). These results suggest that the CA lies with a tilt angle in the interlayer region of the inorganic host matrix. The immobilization of CA is favored in ZHN, with respect to ZHA, because a single-layered phase was identified. A higher thermal stability at 65 °C was observed for ZHN-CA than for ZHA-CA. The evaluation of the release behavior showed a higher percentage of CA released from ZHN than ZHA, and the release mechanism was described by the Elovich model. The hybrid materials show potential characteristics for use as bioactive delivery systems.
Surface-Enhanced Raman Spectroscopy on Hybrid Graphene/Gold Substrates near the Percolation Threshold
Authors: Tatarkin Dmitry E. , Yakubovsky Dmitry I. , Ermolaev Georgy A. , Stebunov Yury V. , Voronov Artem A. , Arsenin Aleksey V. , Volkov Valentyn S. , Novikov Sergey M.
Published: January 2020

Graphene is a promising platform for surface-enhanced Raman spectroscopy (SERS)-active substrates, primarily due to the possibility of quenching photoluminescence and fluorescence. Here we study ultrathin gold films near the percolation threshold fabricated by electron-beam deposition on monolayer CVD graphene. The advantages of such hybrid graphene/gold substrates for surface-enhanced Raman spectroscopy are discussed in comparison with conventional substrates without the graphene layer. The percolation threshold is determined by independent measurements of the sheet resistance and effective dielectric constant by spectroscopic ellipsometry. The surface morphology of the ultrathin gold films is analyzed by the use of scanning electron microscopy (SEM) and atomic force microscopy (AFM), and the thicknesses of the films in addition to the quartz-crystal mass-thickness sensor are also measured by AFM. We experimentally demonstrate that the maximum SERS signal is observed near and slightly below the percolation threshold. In this case, the region of maximum enhancement of the SERS signal can be determined using the figure of merit (FOM), which is the ratio of the real and imaginary parts of the effective dielectric permittivity of the films. SERS measurements on hybrid graphene/gold substrates with the dye Crystal Violet show an enhancement factor of ~105 and also demonstrate the ability of graphene to quench photoluminescence by an average of ~60%.
Metal–Organic Framework-Based Sustainable Nanocatalysts for CO Oxidation
Authors: Lozano Luis A. , Faroldi Betina M. C. , Ulla María A. , Zamaro Juan M.
Published: January 2020

The development of new catalytic nanomaterials following sustainability criteria both in their composition and in their synthesis process is a topic of great current interest. The purpose of this work was to investigate the preparation of nanocatalysts derived from the zirconium metal–organic framework UiO-66 obtained under friendly conditions and supporting dispersed species of non-noble transition elements such as Cu, Co, and Fe, incorporated through a simple incipient wetness impregnation technique. The physicochemical properties of the synthesized solids were studied through several characterization techniques and then they were investigated in reactions of relevance for environmental pollution control, such as the oxidation of carbon monoxide in air and in hydrogen-rich streams (COProx). By controlling the atmospheres and pretreatment temperatures, it was possible to obtain active catalysts for the reactions under study, consisting of Cu-based UiO-66-, bimetallic CuCo–UiO-66-, and CuFe–UiO-6-derived materials. These solids represent new alternatives of nanostructured catalysts based on highly dispersed non-noble active metals.
Centromeric Non-Coding RNAs: Conservation and Diversity in Function
Authors: Ideue Takashi , Tani Tokio
Published: January 2020

Chromosome segregation is strictly regulated for the proper distribution of genetic material to daughter cells. During this process, mitotic chromosomes are pulled to both poles by bundles of microtubules attached to kinetochores that are assembled on the chromosomes. Centromeres are specific regions where kinetochores assemble. Although these regions were previously considered to be silent, some experimental studies have demonstrated that transcription occurs in these regions to generate non-coding RNAs (ncRNAs). These centromeric ncRNAs (cenRNAs) are involved in centromere functions. Here, we describe the currently available information on the functions of cenRNAs in several species.