bluuebunny/crossref_metadata_2025 huggingface dataset:
Feature Ranking and Screening for Class-Imbalanced Metabolomics Data Based on Rank Aggregation Coupled with Re-Balance
Authors: Fu Guang-Hui , Wang Jia-Bao , Zong Min-Jie , Yi Lun-Zhao
Published: June 2021

Feature screening is an important and challenging topic in current class-imbalance learning. Most of the existing feature screening algorithms in class-imbalance learning are based on filtering techniques. However, the variable rankings obtained by various filtering techniques are generally different, and this inconsistency among different variable ranking methods is usually ignored in practice. To address this problem, we propose a simple strategy called rank aggregation with re-balance (RAR) for finding key variables from class-imbalanced data. RAR fuses each rank to generate a synthetic rank that takes every ranking into account. The class-imbalanced data are modified via different re-sampling procedures, and RAR is performed in this balanced situation. Five class-imbalanced real datasets and their re-balanced ones are employed to test the RAR’s performance, and RAR is compared with several popular feature screening methods. The result shows that RAR is highly competitive and almost better than single filtering screening in terms of several assessing metrics. Performing re-balanced pretreatment is hugely effective in rank aggregation when the data are class-imbalanced.
From Klebsiella pneumoniae Colonization to Dissemination: An Overview of Studies Implementing Murine Models
Authors: Joseph Laura , Merciecca Thomas , Forestier Christiane , Balestrino Damien , Miquel Sylvie
Published: June 2021

Klebsiella pneumoniae is a Gram-negative pathogen responsible for community-acquired and nosocomial infections. The strains of this species belong to the opportunistic group, which is comprised of the multidrug-resistant strains, or the hypervirulent group, depending on their accessory genome, which determines bacterial pathogenicity and the host immune response. The aim of this survey is to present an overview of the murine models mimicking K. pneumoniae infectious processes (i.e., gastrointestinal colonization, urinary, pulmonary, and systemic infections), and the bacterial functions deployed to colonize and disseminate into the host. These in vivo approaches are pivotal to develop new therapeutics to limit K. pneumoniae infections via a modulation of the immune responses and/or microbiota.
MALDI-TOF MS in a Medical Mycology Laboratory: On Stage and Backstage
Authors: Robert Marie-Gladys , Cornet Muriel , Hennebique Aurélie , Rasamoelina Tahinamandranto , Caspar Yvan , Pondérand Léa , Bidart Marie , Durand Harmonie , Jacquet Marvin , Garnaud Cécile , Maubon Danièle
Published: June 2021

The implementation of MALDI-TOF MS in medical microbiology laboratories has revolutionized practices and significantly reduced turnaround times of identification processes. However, although bacteriology quickly benefited from the contributions of this technique, adjustments were necessary to accommodate the specific characteristics of fungi. MALDI-TOF MS is now an indispensable tool in clinical mycology laboratories, both for the identification of yeasts and filamentous fungi, and other innovative uses are gradually emerging. Based on the practical experience of our medical mycology laboratory, this review will present the current uses of MALDI-TOF MS and the adaptations we implemented, to allow their practical execution in a daily routine. We will also introduce some less mainstream applications, like those for fungemia, or even still under development, as is the case for the determination of sensitivity to antifungal agents or typing methods.
Comparative Exoproteome Analysis of Streptococcus suis Human Isolates
Authors: de la Torre Esther Prados , Rodríguez-Franco Antonio , Rodríguez-Ortega Manuel J.
Published: June 2021

The swine pathogen Streptococcus suis is a Gram-positive bacterium which causes infections in pigs, with an impact in animal health and in the livestock industry, and it is also an important zoonotic agent. During the infection process, surface and secreted proteins are essential in the interaction between microorganisms and their hosts. Here, we report a comparative proteomic analysis of the proteins released to the extracellular milieu in six human clinical isolates belonging to the highly prevalent and virulent serotype 2. The total secreted content was precipitated and analyzed by GeLC-MS/MS. In the six strains, 144 proteins assigned to each of the categories of extracellular or surface proteins were identified, as well as 680 predicted cytoplasmic proteins, many of which are putative moonlighting proteins. Of the nine predicted signal peptide-I secreted proteins, seven had relevant antigenic potential when they were analyzed through bioinformatic analysis. This is the first work comparing the exoproteome fraction of several human isolates of this important pathogen.
Probiotics Improve Eating Disorders in Mandarin Fish (Siniperca chuatsi) Induced by a Pellet Feed Diet via Stimulating Immunity and Regulating Gut Microbiota
Authors: Chen Xiaoli , Yi Huadong , Liu Shuang , Zhang Yong , Su Yuqin , Liu Xuange , Bi Sheng , Lai Han , Zeng Zeyu , Li Guifeng
Published: June 2021

Eating disorders are directly or indirectly influenced by gut microbiota and innate immunity. Probiotics have been shown to regulate gut microbiota and stimulate immunity in a variety of species. In this study, three kinds of probiotics, namely, Lactobacillus plantarum, Lactobacillus rhamnosus and Clostridium butyricum, were selected for the experiment. The results showed that the addition of three probiotics at a concentration of 108 colony forming unit/mL to the culture water significantly increased the ratio of the pellet feed recipients and survival rate of mandarin fish (Siniperca chuatsi) under pellet-feed feeding. In addition, the three kinds of probiotics reversed the decrease in serum lysozyme and immunoglobulin M content, the decrease in the activity of antioxidant enzymes glutathione and catalase and the decrease in the expression of the appetite-stimulating regulator agouti gene-related protein of mandarin fish caused by pellet-feed feeding. In terms of intestinal health, the three probiotics reduced the abundance of pathogenic bacteria Aeromonas in the gut microbiota and increased the height of intestinal villi and the thickness of foregut basement membrane of mandarin fish under pellet-feed feeding. In general, the addition of the three probiotics can significantly improve eating disorders of mandarin fish caused by pellet feeding.
Novel Sequence Types of Listeria monocytogenes of Different Origin Obtained in the Republic of Serbia
Authors: Bespalova Tatiana Yu. , Mikhaleva Tatiana V. , Meshcheryakova Nadezhda Yu , Kustikova Olga V. , Matovic Kazimir , Dmitrić Marko , Zaitsev Sergey S. , Khizhnyakova Maria A. , Feodorova Valentina A.
Published: June 2021

Listeria monocytogenes, the causative agent of listeriosis, is amongst the major food-borne pathogens in the world that affect mammal species, including humans. This microorganism has been associated with both sporadic episodes and large outbreaks of human listeriosis worldwide, with high mortality rates. In this study, the main sequence types (STs) and clonal complexes (CCs) were investigated in all of the 13 L. monocytogenes strains originating from different sources in the Republic of Serbia in 2004–2019 and that were available in the BIGSdb-Lm database. We found at least 13 STs belonging to the phylogenetic lineages I and II. These strains were represented by ST1/ST3/ST9 of CC1/CC3/CC9, which were common in the majority of the European countries and worldwide, as well as by eight novel STs (ST1232/ST1233/ST1234/ST1235/ST1238/ST1236/ST1237/ST1242) of CC19/CC155/CC5/CC21/CC3/CC315/CC37, and the rare ST32 (clonal complex ST32) and ST734 (CC1), reported in the Republic of Serbia, the EU, for the first time. Our study confirmed the association of CC1 with cases of neuroinfection and abortions among small ruminants, and of CC3 and CC9 with food products of animal origin. The strains isolated in 2019 carried alleles of the internalin genes (inlA/inlB/inlC/inlE) characteristic of the most virulent strains from the hypervirulent CC1. These findings demonstrated the genetic relatedness between L. monocytogenes strains isolated in the Republic of Serbia and worldwide. Our study adds further information about the diversity of the L. monocytogenes genotypes of small ruminants and food products, as the strain distribution in these sources in Serbia had not previously been evaluated.
Genome-Wide Metabolic Reconstruction of the Synthesis of Polyhydroxyalkanoates from Sugars and Fatty Acids by Burkholderia Sensu Lato Species
Authors: Alvarez-Santullano Natalia , Villegas Pamela , Mardones Mario Sepúlveda , Durán Roberto E. , Donoso Raúl , González Angela , Sanhueza Claudia , Navia Rodrigo , Acevedo Francisca , Pérez-Pantoja Danilo , Seeger Michael
Published: June 2021

Burkholderia sensu lato (s.l.) species have a versatile metabolism. The aims of this review are the genomic reconstruction of the metabolic pathways involved in the synthesis of polyhydroxyalkanoates (PHAs) by Burkholderia s.l. genera, and the characterization of the PHA synthases and the pha genes organization. The reports of the PHA synthesis from different substrates by Burkholderia s.l. strains were reviewed. Genome-guided metabolic reconstruction involving the conversion of sugars and fatty acids into PHAs by 37 Burkholderia s.l. species was performed. Sugars are metabolized via the Entner–Doudoroff (ED), pentose-phosphate (PP), and lower Embden–Meyerhoff–Parnas (EMP) pathways, which produce reducing power through NAD(P)H synthesis and PHA precursors. Fatty acid substrates are metabolized via β-oxidation and de novo synthesis of fatty acids into PHAs. The analysis of 194 Burkholderia s.l. genomes revealed that all strains have the phaC, phaA, and phaB genes for PHA synthesis, wherein the phaC gene is generally present in ≥2 copies. PHA synthases were classified into four phylogenetic groups belonging to class I II and III PHA synthases and one outlier group. The reconstruction of PHAs synthesis revealed a high level of gene redundancy probably reflecting complex regulatory layers that provide fine tuning according to diverse substrates and physiological conditions.
Gut Dysbiosis and IL-21 Response in Patients with Severe COVID-19
Authors: Khan Mahejibin , Mathew Bijina J. , Gupta Priyal , Garg Garima , Khadanga Sagar , Vyas Ashish Kumar , Singh Anirudh K.
Published: June 2021

Background: The disease severity, ranging from being asymptomatic to having acute illness, and associated inflammatory responses has suggested that alterations in the gut microbiota may play a crucial role in the development of chronic disorders due to COVID-19 infection. This study describes gut microbiota dysbiosis in COVID-19 patients and its implications relating to the disease. Design: A cross sectional prospective study was performed on thirty RT-PCR-confirmed COVID-19 patients admitted to the All India Institute of Medical Sciences, Bhopal, India, between September 10 and 20, 2020. Ten healthy volunteers were recruited as the control group. IFN, TNF, and IL-21 profiling was conducted using plasma samples, and gut bacterial analysis was performed after obtaining the metagenomics data of stool samples. Results: Patients with a variable COVID-19 severity showed distinct gut microflora and peripheral interleukin-21 levels. A low Firmicute/Bacteroidetes ratio, caused by the depletion of the fibre-utilizing bacteria, F. prausnitzii, B. Plebius, and Prevotella, and an increase in Bacteroidetes has associated gut microbiota dysbiosis with COVID-19 disease severity. Conclusions: The loss of the functional attributes of signature commensals in the gut, due to dysbiosis, is a predisposing factor of COVID-19 pathophysiology.
Rare and Critical Metals in Pyrite, Chalcopyrite, Magnetite, and Titanite from the Vathi Porphyry Cu-Au±Mo Deposit, Northern Greece
Authors: Stergiou Christos L. , Melfos Vasilios , Voudouris Panagiotis , Papadopoulou Lambrini , Spry Paul G. , Peytcheva Irena , Dimitrova Dimitrina , Stefanova Elitsa , Giouri Katerina
Published: June 2021

The Vathi porphyry Cu-Au±Mo deposit is located in the Kilkis ore district, northern Greece. Hydrothermally altered and mineralized samples of latite and quartz monzonite are enriched with numerous rare and critical metals. The present study focuses on the bulk geochemistry and the mineral chemistry of pyrite, chalcopyrite, magnetite, and titanite. Pyrite and chalcopyrite are the most abundant ore minerals at Vathi and are related to potassic, propylitic, and sericitic hydrothermal alterations (A- and D-veins), as well as to the late-stage epithermal overprint (E-veins). Magnetite and titanite are found mainly in M-type veins and as disseminations in the potassic-calcic alteration of quartz monzonite. Disseminated magnetite is also present in the potassic alteration in latite, which is overprinted by sericitic alteration. Scanning electron microscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analyses of pyrite and chalcopyrite reveal the presence of pyrrhotite, galena, and Bi-telluride inclusions in pyrite and enrichments of Ag, Co, Sb, Se, and Ti. Chalcopyrite hosts bornite, sphalerite, galena, and Bi-sulfosalt inclusions and is enriched with Ag, In, and Ti. Inclusions of wittichenite, tetradymite, and cuprobismutite reflect enrichments of Te and Bi in the mineralizing fluids. Native gold is related to A- and D-type veins and is found as nano-inclusions in pyrite. Titanite inclusions characterize magnetite, whereas titanite is a major host of Ce, Gd, La, Nd, Sm, Th, and W.
A Numerical Study of Separation Performance of Vibrating Flip-Flow Screens for Cohesive Particles
Authors: Yu Chi , Geng Runhui , Wang Xinwen
Published: June 2021

Vibrating flip-flow screens (VFFS) are widely used to separate high-viscosity and fine materials. The most remarkable characteristic is that the vibration intensity of the screen frame is only 2–3 g (g represents the gravitational acceleration), while the vibration intensity of the screen surface can reach 30–50 g. This effectively solves the problem of the blocking screen aperture in the screening process of moist particles. In this paper, the approximate state of motion of the sieve mat is realized by setting the discrete rigid motion at multiple points on the elastic sieve mat of the VFFS. The effects of surface energy levels between particles separated via screening performance were compared and analyzed. The results show that the flow characteristics of particles have a great influence on the separation performance. For 8 mm particle screening, the particle’s velocity dominates its movement and screening behavior in the range of 0–8 J/m2 surface energy. In the feeding end region (Sections 1 and 2), with the increase in the surface energy, the particle’s velocity decreases, and the contact time between the particles and the screen surface increases, and so the passage increases. When the surface energy level continues to increase, the particles agglomerate together due to the effect of the cohesive force, and the effect of the particle’s agglomeration is greater than the particle velocity. Due to the agglomeration of particles, the difficulty of particles passing through the screen increases, and the yields of various size fractions in the feeding end decrease to some extent. In the transporting process, the agglomerated particles need to travel a certain distance before depolymerization, and the stronger the adhesive force between particles, the larger the depolymerization distance. Therefore, for the case of higher surface energy, the screening percentage near the discharging end (Sections 3 and 4) is greater. The above research is helpful to better understand and optimize the screening process of VFFS.
Iron-Rich Spherules of Taihu Lake: Origin Hypothesis of Taihu Lake Basin in China
Authors: Zuo Shuhao , Xie Zhidong
Published: June 2021

In this paper, a detailed mineralogical study on iron-rich spherules in Taihu Lake was carried out, and we present a proposed impact-related origin for these iron-rich spherules. The iron-rich spherical concretions in Taihu Lake occur in a specific silty layer formed around ~7 ka B.P., sandwiched between an upper lacustrine deposit layer and a lower hard loess layer, and they are widely distributed and are the most abundant iron-rich concretions in that specific layer in the vicinity of Taihu Lake. The spherules are typically ~0.5 to 3 mm in diameter with a shape very similar to a spherical shape but not exactly rounded and have various apparent aerodynamic shapes, such as spherical, cone, spindle, ellipsoidal, elongated and pear-shaped morphologies. SEM imaging shows that there is no central core and no concentric layers in the spherules. Iron-rich spherical concretions are similar to accretionary lapilli and have a typical colloidal structure with abundant angular quartz grains and trace fragments of clays wrapped in fine cements that are mainly goethite with minor clays and carbon particles. The typical nodule-forming mechanism in aqueous sediments does not sufficiently explain the morphology and internal features of the iron-rich spherules of Taihu Lake, whereas the aerosol formation mechanism under the airburst impact origin hypothesis of the Taihu Lake basin may be a better explanation of the unique mineralogy of the spherules. Specifically, airburst impact plumes could be the reaction chambers of the aerosol to form the accretionary lapilli with a colloidal texture for the interior, while a dense shell and semi-plastic morphological features can form in the falling processes from higher altitudes in the plume.
Determinants for α4β2 vs. α3β4 Subtype Selectivity of Pyrrolidine-Based nAChRs Ligands: A Computational Perspective with Focus on Recent cryo-EM Receptor Structures
Authors: Bavo Francesco , Pallavicini Marco , Appiani Rebecca , Bolchi Cristiano
Published: June 2021

The selectivity of α4β2 nAChR agonists over the α3β4 nicotinic receptor subtype, predominant in ganglia, primarily conditions their therapeutic range and it is still a complex and challenging issue for medicinal chemists and pharmacologists. Here, we investigate the determinants for such subtype selectivity in a series of more than forty α4β2 ligands we have previously reported, docking them into the structures of the two human subtypes, recently determined by cryo-electron microscopy. They are all pyrrolidine based analogues of the well-known α4β2 agonist N-methylprolinol pyridyl ether A-84543 and differ in the flexibility and pattern substitution of their aromatic portion. Indeed, the direct or water mediated interaction with hydrophilic residues of the relatively narrower β2 minus side through the elements decorating the aromatic ring and the stabilization of the latter by facing to the not conserved β2-Phe119 result as key distinctive features for the α4β2 affinity. Consistently, these compounds show, despite the structural similarity, very different α4β2 vs. α3β4 selectivities, from modest to very high, which relate to rigidity/extensibility degree of the portion containing the aromatic ring and to substitutions at the latter. Furthermore, the structural rationalization of the rat vs. human differences of α4β2 vs. α3β4 selectivity ratios is here proposed.
New Insights on Volatile Components of Vanilla planifolia Cultivated in Taiwan
Authors: Yeh Chih-Hsin , Chen Kai-Yi , Chou Chia-Yi , Liao Hsin-Yi , Chen Hsin-Chun
Published: June 2021

Vanilla (Vanilla planifolia) is a precious natural flavoring that is commonly used throughout the world. In the past, all vanilla used in Taiwan was imported; however, recent breakthroughs in cultivation and processing technology have allowed Taiwan to produce its own supply of vanilla. In this study, headspace solid-phase microextraction (HS-SPME) combined with GC-FID and GC-MS was used to analyze the volatile components of vanilla from different origins produced in Taiwan under different cultivation and processing conditions. The results of our study revealed that when comparing different harvest maturities, the composition diversity and total volatile content were both higher when the pods were matured for more than 38 weeks. When comparing different killing conditions, we observed that the highest vanillin percentage was present after vanilla pods were killed three times in 65 °C treatments for 1 min each. From the experiment examining the addition of different strains, the PCA results revealed that the volatiles of vanilla that was processed with Dekkera bruxellensis and Bacillus subtilis was clearly distinguished from which obtained by processing with the other strains. Vanilla processed with B. subtilis contained 2-ethyl-1-hexanol, and this was not detected in other vanillas. Finally, when comparing the vanillin percentage from seven different regions in Taiwan, vanilla percentage from Taitung and Taoyuan Longtan were the highest.
Development and Characterization of Novel Biopolymer Derived from Abelmoschus esculentus L. Extract and Its Antidiabetic Potential
Authors: Elkhalifa Abd Elmoneim O. , Al-Shammari Eyad , Adnan Mohd , Alcantara Jerold C. , Mehmood Khalid , Eltoum Nagat Elzein , Awadelkareem Amir Mahgoub , Khan Mushtaq Ahmad , Ashraf Syed Amir
Published: June 2021

Abelmoschus esculentus (Okra) is an important vegetable crop, widely cultivated around the world due to its high nutritional significance along with several health benefits. Different parts of okra including its mucilage have been currently studied for its role in various therapeutic applications. Therefore, we aimed to develop and characterize the okra mucilage biopolymer (OMB) for its physicochemical properties as well as to evaluate its in vitro antidiabetic activity. The characterization of OMB using Fourier-transform infrared spectroscopy (FT-IR) revealed that okra mucilage containing polysaccharides lies in the bandwidth of 3279 and 1030 cm−1, which constitutes the fingerprint region of the spectrum. In addition, physicochemical parameters such as percentage yield, percentage solubility, and swelling index were found to be 2.66%, 96.9%, and 5, respectively. A mineral analysis of newly developed biopolymers showed a substantial amount of calcium (412 mg/100 g), potassium (418 mg/100 g), phosphorus (60 mg/100 g), iron (47 mg/100 g), zinc (16 mg/100 g), and sodium (9 mg/100 g). The significant antidiabetic potential of OMB was demonstrated using α-amylase and α-glucosidase enzyme inhibitory assay. Further investigations are required to explore the newly developed biopolymer for its toxicity, efficacy, and its possible utilization in food, nutraceutical, as well as pharmaceutical industries.
Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment
Authors: Yu Jialin , Qiu Huayu , Yin Shouchun , Wang Hebin , Li Yang
Published: June 2021

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.
Classical Food Quality Attributes and the Metabolic Profile of Cambuci, a Native Brazilian Atlantic Rainforest Fruit
Authors: Spricigo Poliana Cristina , Correia Banny Silva Barbosa , Borba Karla Rodrigues , Taver Isabela Barroso , Machado Guilherme de Oliveira , Wilhelms Renan Ziemann , Queiroz Junior Luiz Henrique Keng , Jacomino Angelo Pedro , Colnago Luiz Alberto
Published: June 2021

The cambuci is a native Brazilian fruit from the Atlantic Forest biome. A soft and astringent pulp, a green color, and a sweet aroma are its main characteristics. Classical food quality attributes (fresh fruit mass, fruit height, diameters, total soluble solid, titratable acidity, and ratio) and the metabolic profile from ten accessions from three different locations were analyzed herein by analytical methods (refractometry and neutralization titration) and nuclear magnetic resonance spectroscopy. Concerning sugar content, sucrose was the predominant compound, with glucose and fructose alternating in second, depending on the accession. Citric acid was the most relevant acid, followed by shikimic and quinic acids in quite variable amounts. These three main acids vary in amounts for each accession. Ascorbic acid content emerges as an important quality attribute and makes this fruit nutritionally attractive, due to values comparable to those contained in citric fruits. The main amino acids identified in cambuci were glutamic acid individually or in comprising the tripeptide glutathione (glutamic acid, cysteine, glycine). The quality diversity of the evaluated accessions suggests the potentiality of cambuci use in future breeding programs.
Quercetin and Rutin as Modifiers of Aphid Probing Behavior
Authors: Stec Katarzyna , Kordan Bożena , Gabryś Beata
Published: June 2021

Rutin and its aglycone quercetin occur in the fruits, leaves, seeds, and grains of many plant species and are involved in plant herbivore interactions. We studied the effect of the exogenous application of rutin and quercetin on the probing behavior (= stylet penetration activities in plant tissues) of Acyrthosiphon pisum on Pisum sativum, Myzus persicae on Brassica rapa ssp. pekinensis, and Rhopalosiphum padi on Avena sativa using the electrical penetration graph technique (EPG = electropenetrography). The reaction of aphids to quercetin and rutin and the potency of the effect depended on aphid species, the flavonol, and flavonol concentration. Quercetin promoted probing activities of A. pisum within non-phloem and phloem tissues, which was demonstrated in the longer duration of probes and a trend toward longer duration of sap ingestion, respectively. M. persicae reached phloem in a shorter time on quercetin-treated B. rapa than on the control. Rutin caused a delay in reaching sieve elements by A. pisum and deterred probing activities of M. persicae within non-phloem tissues. Probing of R. padi was not affected by quercetin or rutin. The potency of behavioral effects increased as the applied concentrations of flavonols increased. The prospects of using quercetin and rutin in plant protection are discussed.
The Influence of Ripeness on the Phenolic Content, Antioxidant and Antimicrobial Activities of Pumpkins (Cucurbita moschata Duchesne)
Authors: Mokhtar Meriem , Bouamar Sarah , Di Lorenzo Arianna , Temporini Caterina , Daglia Maria , Riazi Ali
Published: June 2021

Cucurbita moschata Duchesne (Cucurbitaceae) is a plant food highly appreciated for the content of nutrients and bioactive compounds, including polyphenols and carotenoids, which contribute to its antioxidant and antimicrobial capacities. The purpose of this study was to identify phenolic acids and flavonoids of Cucurbita moschata Duchesne using high-performance liquid chromatography–diode array detection–electrospray ionization tandem mass spectrometry (HPLC–DAD–ESI-MS) at different ripening stages (young, mature, ripened) and determine its antioxidant and antimicrobial activities. According to the results, phenolic acids and flavonoids were dependent on the maturity stage. The mature fruits contain the highest total phenolic and flavonoids contents (97.4 mg GAE. 100 g−1 and 28.6 mg QE. 100 g−1).A total of 33 compounds were identified. Syringic acid was the most abundant compound (37%), followed by cinnamic acid (12%) and protocatechuic acid (11%). Polyphenol extract of the mature fruits showed the highest antioxidant activity when measured by DPPH (0.065 μmol TE/g) and ABTS (0.074 μmol TE/g) assays. In the antimicrobial assay, the second stage of ripening had the highest antibacterial activity. Staphylococcus aureus was the most sensitive strain with an inhibition zone of 12 mm and a MIC of 0.75 mg L−1. The lowest inhibition zone was obtained with Salmonella typhimurium (5 mm), and the MIC value was 10 mg L−1.
Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis
Authors: Abdullah Nada , Tamimi Yahya , Dobretsov Sergey , Balushi Najwa Al , Alshekaili Jalila , Al Balushi Hamed , Al Kindi Mahmood , Hassan Syed Imran , Bahlani Shadia Al , Tsang Benjamin K. , Burney Ikram A.
Published: June 2021

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.
Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation
Authors: Woziwodzka Anna , Krychowiak-Maśnicka Marta , Gołuński Grzegorz , Felberg Anna , Borowik Agnieszka , Wyrzykowski Dariusz , Piosik Jacek
Published: June 2021

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M−1 and enthalpy change values up to −4 kJ·M−1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.
Synthesis and Characterization of 1,10-Phenanthroline-mono-N-oxides
Authors: Najóczki Ferenc , Szabó Mária , Lihi Norbert , Udvardy Antal , Fábián István
Published: June 2021

N-oxides of N-heteroaromatic compounds find widespread applications in various fields of chemistry. Although the strictly planar aromatic structure of 1,10-phenanthroline (phen) is expected to induce unique features of the corresponding N-oxides, so far the potential of these compounds has not been explored. In fact, appropriate procedure has not been reported for synthesizing these derivatives of phen. Now, we provide a straightforward method for the synthesis of a series of mono-N-oxides of 1,10-phenanthrolines. The parent compounds were oxidized by a green oxidant, peroxomonosulfate ion in acidic aqueous solution. The products were obtained in high quality and at good to excellent yields. A systematic study reveals a clear-cut correlation between the basicity of the compounds and the electronic effects of the substituents on the aromatic ring. The UV spectra of these compounds were predicted by DFT calculations at the TD-DFT/TPSSh/def2-TZVP level of theory.
Unveiling the Ionic Diels–Alder Reactions within the Molecular Electron Density Theory
Authors: Domingo Luis R. , Ríos-Gutiérrez Mar , Aurell María José
Published: June 2021

The ionic Diels–Alder (I-DA) reactions of a series of six iminium cations with cyclopentadiene have been studied within the Molecular Electron Density Theory (MEDT). The superelectrophilic character of iminium cations, ω > 8.20 eV, accounts for the high reactivity of these species participating in I-DA reactions. The activation energies are found to be between 13 and 20 kcal·mol−1 lower in energy than those associated with the corresponding Diels–Alder (DA) reactions of neutral imines. These reactions are low endo selective as a consequence of the cationic character of the TSs, but highly regioselective. Solvents have poor effects on the relative energies, and an unappreciable effect on the geometries. In acetonitrile, the activation energies increase slightly as a consequence of the better solvation of the iminium cations than the cationic TSs. Electron localization function (ELF) topological analysis of the bonding changes along the I-DA reactions shows that they are very similar to those in polar DA reactions. The present MEDT study establishes that the global electron density transfer (GEDT) taking place at the TSs of I-DA reactions, and not steric (Pauli) repulsions such as have been recently proposed, are responsible for the features of these types of DA reactions.
Sono-Biosynthesis and Characterization of AuNPs from Danube Delta Nymphaea alba Root Extracts and Their Biological Properties
Authors: Cudalbeanu Mihaela , Peitinho David , Silva Francisco , Marques Rosa , Pinheiro Teresa , Ferreira Ana C. , Marques Fernanda , Paulo António , Soeiro Catarina F. , Sousa Sílvia Andreia , Leitão Jorge Humberto , Tăbăcaru Aurel , Avramescu Sorin Marius , Dinica Rodica Mihaela , Campello Maria Paula Cabral
Published: June 2021

Root extracts from Danube Delta Nymphaea alba were used to prepare gold nanoparticles (AuNPRn) by reducing HAuCl4 at different pHs (6.4–8.4) using ultrasonic irradiation: an easy, cheap, eco-friendly and green approach. Their antibacterial and anticancer activities were evaluated against Staphylococcus aureus and Escherichia coli, and A2780 ovarian cancer cells, respectively. The AuNPRn were characterized concerning their phytoconstituents (polyphenols, flavonoids and condensed tannins) and gold content. All of the nanoparticles were negatively charged. AuNPRn exhibited a hydrodynamic size distribution ranging from 32 nm to 280 nm, with the larger nanoparticles being obtained with an Au/root extract ratio of 0.56, pH 7 and 10 min of sonication (AuNPR1), whereas the smallest were obtained with an Au/root extract ratio of 0.24, pH 7.8 and 40 min of sonication (AuNPR4). The TEM/SEM images showed that the AuNPRn had different shapes. The ATR-FTIR indicated that AuNPRn interact mainly with hydroxyl groups present in the polyphenol compounds, which also confirm their high antioxidant capacity, except for AuNPR2 obtained at pH 6.4. Among the AuNPRn, the smallest ones exhibited enhanced antimicrobial and anticancer activities.
Long Non-Coding RNAs in the Control of Gametogenesis: Lessons from Fission Yeast
Authors: Andric Vedrana , Rougemaille Mathieu
Published: June 2021

Long non-coding RNAs (lncRNAs) contribute to cell fate decisions by modulating genome expression and stability. In the fission yeast Schizosaccharomyces pombe, the transition from mitosis to meiosis results in a marked remodeling of gene expression profiles, which ultimately ensures gamete production and inheritance of genetic information to the offspring. This key developmental process involves a set of dedicated lncRNAs that shape cell cycle-dependent transcriptomes through a variety of mechanisms, including epigenetic modifications and the modulation of transcription, post-transcriptional and post-translational regulations, and that contribute to meiosis-specific chromosomal events. In this review, we summarize the biology of these lncRNAs, from their identification to mechanism of action, and discuss their regulatory role in the control of gametogenesis.
Emerging Role of MicroRNA-200 Family in Dentistry
Authors: Hsieh Pei-Ling , Huang Chun-Chung , Yu Cheng-Chia
Published: June 2021

MicroRNAs (miRNAs) are endogenous non-coding RNAs ~22 nucleotides in length, which have been shown to participate in various biological processes. As one of the most researched miRNAs, the miR-200 family has been found to regulate several factors that are associated with the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) behavior. In this review, we briefly summarize the background of the miR-200 family and their implication in various dental diseases. We focus on the expression changes, biological functions, and clinical significance of the miR-200 family in oral cancer; periodontitis; oral potentially malignant disorder; gingival overgrowth; and other periodontal diseases. Additionally, we discuss the use of the miR-200 family as molecular biomarkers for diagnosis, prognostic, and therapeutic application.
Surfactant-Assisted Distal Pulmonary Distribution of Budesonide Revealed by Mass Spectrometry Imaging
Authors: Zecchi Riccardo , Franceschi Pietro , Tigli Laura , Pioselli Barbara , Mileo Valentina , Murgia Xabier , Salomone Fabrizio , Pieraccini Giuseppe , Usada Haruo , Schmidt Augusto F. , Hillman Noah H. , Kemp Matthew W. , Jobe Alan H.
Published: June 2021

Direct lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lung.
A Biophysical Insight of Camptothecin Biodistribution: Towards a Molecular Understanding of Its Pharmacokinetic Issues
Authors: Almeida Andreia , Fernandes Eduarda , Sarmento Bruno , Lúcio Marlene
Published: June 2021

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood–brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS = 5.75 ± 0.932 L·Kg−1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.
Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
Authors: AlAli Amer S. , Aldawsari Mohammed F. , Alalaiwe Ahmed , Almutairy Bjad K. , Al-Shdefat Ramadan , Walbi Ismail A. , Fayed Mohamed H.
Published: June 2021

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.
Development of Innovative Chewable Gel Tablets Containing Nutmeg Essential Oil Microcapsules and Their Physical Properties Evaluation
Authors: Matulyte Inga , Marksa Mindaugas , Bernatoniene Jurga
Published: June 2021

Chewable gel tablets are a dosed pharmaceutical form, which can have an active substance, pharmacological effect, or value of nutrition. The texture of these tablets is soft, springy, flexible, and elastic—this is influenced by the chosen ingredients. The aim of this study was to prepare chewable gel tablets with nutmeg essential oil-loaded microcapsules and determine the volatile compounds released from this pharmaceutical form. Gel tablets were prepared by using gelatin as basis, nutmeg essential oil as active compound, and natural ingredients: thyme-sugar syrup, thyme extract, and citric acid as taste and color additives. Texture properties were measured by a texture analyzer. The release of volatile compounds from nutmeg essential oil and gel tablets were analyzed by headspace-gas chromatography with mass spectroscopy in control and artificial saliva conditions in vitro. Nutmeg essential oil microcapsules had influence on the gel tablet’s physical properties (p < 0.05, by comparing tablets without glycerol and relative sample with glycerol); glycerol protects the tablets from the formation of sugar crystals on top and keeps good physical parameters (p < 0.05). A total of 12 volatile compounds were identified in nutmeg essential oil, and the six compounds with the highest amounts were selected as controls. Gel tablets prolong the release time of volatile compounds and reduce the amount of the compounds compared to the microcapsules (p < 0.05).
Holography and the Luxury Industry
Authors: Bove V. Michael , Reader Nicole A.
Published: June 2021

The luxury goods industry and holography have a lengthy history together. In this article, we review the applications of holography to the industry and the relevant technical requirements, in particular when the hologram itself is the luxury item, when the hologram is used to promote luxury items, and when the hologram is used for authentication of luxury items. We then explore some possible scenarios for the evolution of this relationship.