bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Complexity of Finding the Maximum Entropy Compatible Quantum State
Authors: Di Giorgio Serena , Mateus Paulo
Published: January 2021

Herein we study the problem of recovering a density operator from a set of compatible marginals, motivated by limitations of physical observations. Given that the set of compatible density operators is not singular, we adopt Jaynes’ principle and wish to characterize a compatible density operator with maximum entropy. We first show that comparing the entropy of compatible density operators is complete for the quantum computational complexity class QSZK, even for the simplest case of 3-chains. Then, we focus on the particular case of quantum Markov chains and trees and establish that for these cases, there exists a procedure polynomial in the number of subsystems that constructs the maximum entropy compatible density operator. Moreover, we extend the Chow–Liu algorithm to the same subclass of quantum states.
Convergence in Total Variation of Random Sums
Authors: Pratelli Luca , Rigo Pietro
Published: January 2021

Let (Xn) be a sequence of real random variables, (Tn) a sequence of random indices, and (τn) a sequence of constants such that τn→∞. The asymptotic behavior of Ln=(1/τn)∑i=1TnXi, as n→∞, is investigated when (Xn) is exchangeable and independent of (Tn). We give conditions for Mn=τn(Ln−L)⟶M in distribution, where L and M are suitable random variables. Moreover, when (Xn) is i.i.d., we find constants an and bn such that supA∈B(R)|P(Ln∈A)−P(L∈A)|≤an and supA∈B(R)|P(Mn∈A)−P(M∈A)|≤bn for every n. In particular, Ln→L or Mn→M in total variation distance provided an→0 or bn→0, as it happens in some situations.
Some Applications of the Wright Function in Continuum Physics: A Survey
Authors: Povstenko Yuriy
Published: January 2021

The Wright function is a generalization of the exponential function and the Bessel functions. Integral relations between the Mittag–Leffler functions and the Wright function are presented. The applications of the Wright function and the Mainardi function to description of diffusion, heat conduction, thermal and diffusive stresses, and nonlocal elasticity in the framework of fractional calculus are discussed.
Modeling and Sensitivity Analysis of the Forward Osmosis Process to Predict Membrane Flux Using a Novel Combination of Neural Network and Response Surface Methodology Techniques
Authors: Jawad Jasir , Hawari Alaa , Zaidi Syed
Published: January 2021

The forward osmosis (FO) process is an emerging technology that has been considered as an alternative to desalination due to its low energy consumption and less severe reversible fouling. Artificial neural networks (ANNs) and response surface methodology (RSM) have become popular for the modeling and optimization of membrane processes. RSM requires the data on a specific experimental design whereas ANN does not. In this work, a combined ANN-RSM approach is presented to predict and optimize the membrane flux for the FO process. The ANN model, developed based on an experimental study, is used to predict the membrane flux for the experimental design in order to create the RSM model for optimization. A Box–Behnken design (BBD) is used to develop a response surface design where the ANN model evaluates the responses. The input variables were osmotic pressure difference, feed solution (FS) velocity, draw solution (DS) velocity, FS temperature, and DS temperature. The R2 obtained for the developed ANN and RSM model are 0.98036 and 0.9408, respectively. The weights of the ANN model and the response surface plots were used to optimize and study the influence of the operating conditions on the membrane flux.
Novel Models of Streptococcus canis Colonization and Disease Reveal Modest Contributions of M-Like (SCM) Protein
Authors: Cornax Ingrid , Zulk Jacob , Olson Joshua , Fulde Marcus , Nizet Victor , Patras Kathryn A
Published: January 2021

Streptococcus canis is a common colonizing bacterium of the urogenital tract of cats and dogs that can also cause invasive disease in these animal populations and in humans. Although the virulence mechanisms of S. canis are not well-characterized, an M-like protein, SCM, has recently identified been as a potential virulence factor. SCM is a surface-associated protein that binds to host plasminogen and IgGs suggesting its possible importance in host-pathogen interactions. In this study, we developed in vitro and ex vivo blood component models and murine models of S. canis vaginal colonization, systemic infection, and dermal infection to compare the virulence potential of the zoonotic S. canis vaginal isolate G361 and its isogenic SCM-deficient mutant (G361∆scm). We found that while S. canis establishes vaginal colonization and causes invasive disease in vivo, the contribution of the SCM protein to virulence phenotypes in these models is modest. We conclude that SCM is dispensable for invasive disease in murine models and for resistance to human blood components ex vivo, but may contribute to mucosal persistence, highlighting a potential contribution to the recently appreciated genetic diversity of SCM across strains and hosts.
Detection of SARS-CoV-2 and Other Infectious Agents in Lower Respiratory Tract Samples Belonging to Patients Admitted to Intensive Care Units of a Tertiary-Care Hospital, Located in an Epidemic Area, during the Italian Lockdown
Authors: Calderaro Adriana , Buttrini Mirko , Montecchini Sara , Piccolo Giovanna , Martinelli Monica , Dell'Anna Maria Loretana , Di Maio Alan , Arcangeletti Maria Cristina , Maccari Clara , De Conto Flora , Chezzi Carlo
Published: January 2021

The aim of this study was the detection of infectious agents from lower respiratory tract (LRT) samples in order to describe their distribution in patients with severe acute respiratory failure and hospitalized in intensive care units (ICU) in an Italian tertiary-care hospital. LRT samples from 154 patients admitted to ICU from 27 February to 10 May 2020 were prospectively examined for respiratory viruses, including SARS-CoV-2, bacteria and/or fungi. SARS-CoV-2 was revealed in 90 patients (58.4%, 72 males, mean age 65 years). No significant difference was observed between SARS-CoV-2 positives and SARS-CoV-2 negatives with regard to sex, age and bacterial and/or fungal infections. Nonetheless, fungi were more frequently detected among SARS-CoV-2 positives (44/54, 81.4%, p = 0.0053). Candida albicans was the overall most frequently isolated agent, followed by Enterococcus faecalis among SARS-CoV-2 positives and Staphylococcus aureus among SARS-CoV-2 negatives. Overall mortality rate was 40.4%, accounting for 53 deaths: 37 among SARS-CoV-2 positives (mean age 69 years) and 16 among SARS-CoV-2 negatives (mean age 63 years). This study highlights the different patterns of infectious agents between the two patient categories: fungi were prevalently involved among SARS-CoV-2-positive patients and bacteria among the SARS-CoV-2-negative patients. The different therapies and the length of the ICU stay could have influenced these different patterns of infectious agents.
The Role of Polyphosphate in Motility, Adhesion, and Biofilm Formation in Sulfolobales
Authors: Recalde Alejandra , van Wolferen Marleen , Sivabalasarma Shamphavi , Albers Sonja-Verena , Navarro Claudio A. , Jerez Carlos A.
Published: January 2021

Polyphosphates (polyP) are polymers of orthophosphate residues linked by high-energy phosphoanhydride bonds that are important in all domains of life and function in many different processes, including biofilm development. To study the effect of polyP in archaeal biofilm formation, our previously described Sa. solfataricus polyP (−) strain and a new polyP (−) S. acidocaldarius strain generated in this report were used. These two strains lack the polymer due to the overexpression of their respective exopolyphosphatase gene (ppx). Both strains showed a reduction in biofilm formation, decreased motility on semi-solid plates and a diminished adherence to glass surfaces as seen by DAPI (4′,6-diamidino-2-phenylindole) staining using fluorescence microscopy. Even though arlB (encoding the archaellum subunit) was highly upregulated in S. acidocardarius polyP (−), no archaellated cells were observed. These results suggest that polyP might be involved in the regulation of the expression of archaellum components and their assembly, possibly by affecting energy availability, phosphorylation or other phenomena. This is the first evidence indicating polyP affects biofilm formation and other related processes in archaea.
The Stable Matching Problem in TBEV Enzootic Circulation: How Important Is the Perfect Tick-Virus Match?
Authors: Liebig Katrin , Boelke Mathias , Grund Domenic , Schicht Sabine , Bestehorn-Willmann Malena , Chitimia-Dobler Lidia , Dobler Gerhard , Jung Klaus , Becker Stefanie C.
Published: January 2021

Tick-borne encephalitis virus (TBEV), like other arthropod-transmitted viruses, depends on specific vectors to complete its enzootic cycle. It has been long known that Ixodes ricinus ticks constitute the main vector for TBEV in Europe. In contrast to the wide distribution of the TBEV vector, the occurrence of TBEV transmission is focal and often restricted to a small parcel of land, whereas surrounding areas with seemingly similar habitat parameters are free of TBEV. Thus, the question arises which factors shape this focal distribution of TBEV in the natural habitat. To shed light on factors driving TBEV-focus formation, we used tick populations from two TBEV-foci in Lower Saxony and two TBEV-foci from Bavaria with their respective virus isolates as a showcase to analyze the impact of specific virus isolate-tick population relationships. Using artificial blood feeding and field-collected nymphal ticks as experimental means, our investigation showed that the probability of getting infected with the synonymous TBEV isolate as compared to the nonsynonymous TBEV isolate was elevated but significantly higher only in one of the four TBEV foci. More obviously, median viral RNA copy numbers were significantly higher in the synonymous virus–tick population pairings. These findings may present a hint for a coevolutionary adaptation of virus and tick populations.
Improved Plasmid-Based Inducible and Constitutive Gene Expression in Corynebacterium glutamicum
Authors: Henke Nadja A. , Krahn Irene , Wendisch Volker F.
Published: January 2021

Corynebacterium glutamicum has been safely used in white biotechnology for the last 60 years and the portfolio of new pathways and products is increasing rapidly. Hence, expression vectors play a central role in discovering endogenous gene functions and in establishing heterologous gene expression. In this work, new expression vectors were designed based on two strategies: (i) a library screening of constitutive native and synthetic promoters and (ii) an increase of the plasmid copy number. Both strategies were combined and resulted in a very strong expression and overproduction of the fluorescence protein GfpUV. As a second test case, the improved vector for constitutive expression was used to overexpress the endogenous xylulokinase gene xylB in a synthetic operon with xylose isomerase gene xylA from Xanthomonas campestris. The xylose isomerase activity in crude extracts was increased by about three-fold as compared to that of the parental vector. In terms of application, the improved vector for constitutive xylA and xylB expression was used for production of the N-methylated amino acid sarcosine from monomethylamine, acetate, and xylose. As a consequence, the volumetric productivity of sarcosine production was 50% higher as compared to that of the strain carrying the parental vector.
Prospectivity Mapping for Magmatic-Related Seafloor Massive Sulfide on the Mid-Atlantic Ridge Applying Weights-of-Evidence Method Based on GIS
Authors: Liu Lushi , Lu Jilong , Tao Chunhui , Liao Shili
Published: January 2021

The Mid-Atlantic Ridge belongs to slow-spreading ridges. Hannington predicted that there were a large number of mineral resources on slow-spreading ridges; however, seafloor massive sulfide deposits usually develop thousands of meters below the seafloor, which make them extremely difficult to explore. Therefore, it is necessary to use mineral prospectivity mapping to narrow the exploration scope and improve exploration efficiency. Recently, Fang and Shao conducted mineral prospectivity mapping of seafloor massive sulfide on the northern Mid-Atlantic Ridge, but the mineral prospectivity mapping of magmatic-related seafloor massive sulfide on the whole Mid-Atlantic Ridge scale has not yet been carried out. In this study, 11 types of data on magmatic-related seafloor massive sulfide mineralization were collected on the Mid-Atlantic Ridge, namely water depth, slope, oceanic crust thickness, large faults, small faults, ridge, bedrock age, spreading rate, Bouguer gravity, and magnetic and seismic point density. Then, the favorable information was extracted from these data to establish 11 predictive maps and to create a mineral potential model. Finally, the weights-of-evidence method was applied to conduct mineral prospectivity mapping. Weight values indicate that oceanic crust thickness, large faults, and spreading rate are the most important prospecting criteria in the study area, which correspond with important ore-controlling factors of magmatic-related seafloor massive sulfide on slow-spreading ridges. This illustrates that the Mid-Atlantic Ridge is a typical slow-spreading ridge, and the mineral potential model presented in this study can also be used on other typical slow-spreading ridges. Seven zones with high posterior probabilities but without known hydrothermal fields were delineated as prospecting targets. The results are helpful for narrowing the exploration scope on the Mid-Atlantic Ridge and can guide the investigation of seafloor massive sulfide resources efficiently.
Specific Refractory Gold Flotation and Bio-Oxidation Products: Research Overview
Authors: Asamoah Richmond K.
Published: January 2021

This paper presents a research overview, reconciling key and useful case study findings, towards uncovering major causes of gold refractoriness and maximising extraction performance of specific gold flotation and bio-oxidation products. Through systematic investigation of the ore mineralogical and gold deportment properties, leaching mechanisms, and kinetic behaviour and pulp rheology, it was observed that the predominant cause of the poor extraction efficacy of one bio-oxidised product is the presence of recalcitrant sulphate minerals (e.g., jarosite and gypsum) produced during the oxidation process. This was followed by carbonaceous matter and other gangue minerals such as muscovite, quartz, and rutile. The underpining leaching mechanism and kinetics coupled with the pulp rheology were influenced by the feed mineralogy/chemistry, time, agitation/shear rate, interfacial chemistry, pH modifier type, and mechano-chemical activation. For instance, surface exposure of otherwise unavailable gold particles by mechano-chemical activation enhanced the gold leaching rate and yield. This work reflect the remarkable impact of subtle deposit feature changes on extraction performance.
Selected β2-, β3- and β2,3-Amino Acid Heterocyclic Derivatives and Their Biological Perspective
Authors: Bąchor Urszula , Mączyński Marcin
Published: January 2021

Heterocyclic moieties, especially five and six-membered rings containing nitrogen, oxygen or sulfur atoms, are broadly distributed in nature. Among them, synthetic and natural alike are pharmacologically active compounds and have always been at the forefront of attention due to their pharmacological properties. Heterocycles can be divided into different groups based on the presence of characteristic structural motifs. The presence of β-amino acid and heterocyclic core in one compound is very interesting; additionally, it very often plays a vital role in their biological activity. Usually, such compounds are not considered to be chemicals containing a β-amino acid motif; however, considering them as this class of compounds may open new routes of their preparation and application as new drug precursors or even drugs. The possibility of their application as nonproteinogenic amino acid residues in peptide or peptide derivatives synthesis to prepare a new class of compounds is also promising. This review highlights the actual state of knowledge about β-amino acid moiety-containing heterocycles presenting antiviral, anti-inflammatory, antibacterial compounds, anaplastic lymphoma kinase (ALK) inhibitors, as well as agonist and antagonists of the receptors.
Synthesis of Silsesquioxanes with Substituted Triazole Ring Functionalities and Their Coordination Ability
Authors: Rzonsowska Monika , Kozakiewicz Katarzyna , Mituła Katarzyna , Duszczak Julia , Kubicki Maciej , Dudziec Beata
Published: January 2021

A synthesis of a series of mono-T8 and difunctionalized double-decker silsesquioxanes bearing substituted triazole ring(s) has been reported within this work. The catalytic protocol for their formation is based on the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) process. Diverse alkynes were in the scope of our interest—i.e., aryl, hetaryl, alkyl, silyl, or germyl—and the latter was shown to be the first example of terminal germane alkyne which is reactive in the applied process’ conditions. From the pallet of 15 compounds, three of them with pyridine-triazole and thiophenyl-triazole moiety attached to T8 or DDSQ core were verified in terms of their coordinating properties towards selected transition metals, i.e., Pd(II), Pt(II), and Rh(I). The studies resulted in the formation of four SQs based coordination compounds that were obtained in high yields up to 93% and their thorough spectroscopic characterization is presented. To our knowledge, this is the first example of the DDSQ-based molecular complex possessing bidentate pyridine-triazole ligand binding two Pd(II) ions.
Targeting S100B with Peptides Encoding Intrinsic Aggregation-Prone Sequence Segments
Authors: Cristóvão Joana S. , Romão Mariana A. , Gallardo Rodrigo , Schymkowitz Joost , Rousseau Frederic , Gomes Cláudio M.
Published: January 2021

S100 proteins assume a diversity of oligomeric states including large order self-assemblies, with an impact on protein structure and function. Previous work has uncovered that S100 proteins, including S100B, are prone to undergo β-aggregation under destabilizing conditions. This propensity is encoded in aggregation-prone regions (APR) mainly located in segments at the homodimer interface, and which are therefore mostly shielded from the solvent and from deleterious interactions, under native conditions. As in other systems, this characteristic may be used to develop peptides with pharmacological potential that selectively induce the aggregation of S100B through homotypic interactions with its APRs, resulting in functional inhibition through a loss of function. Here we report initial studies towards this goal. We applied the TANGO algorithm to identify specific APR segments in S100B helix IV and used this information to design and synthesize S100B-derived APR peptides. We then combined fluorescence spectroscopy, transmission electron microscopy, biolayer interferometry, and aggregation kinetics and determined that the synthetic peptides have strong aggregation propensity, interact with S100B, and may promote co-aggregation reactions. In this framework, we discuss the considerable potential of such APR-derived peptides to act pharmacologically over S100B in numerous physiological and pathological conditions, for instance as modifiers of the S100B interactome or as promoters of S100B inactivation by selective aggregation.
Preamble from the Guest Editor of Special Issue “DFT Quantum-Chemical Calculation of Metal Clusters”
Authors: Mikhailov Oleg V.
Published: January 2021

As known, the concept of “cluster” is collective and includes substances that are quite diverse in composition and chemical structure [...]
Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence
Authors: Hirano Motoharu , Saito Chihiro , Yokoo Hidetomo , Goto Chihiro , Kawano Ryuji , Misawa Takashi , Demizu Yosuke
Published: January 2021

Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.
Colistimethate Acidic Hydrolysis Revisited: Arrhenius Equation Modeling Using UPLC-QToF MS
Authors: Dagla Ioanna , Tsarbopoulos Anthony , Gikas Evagelos
Published: January 2021

Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a result of high neuro- and nephro-toxicity. The measurement of CMS levels in patients’ biological fluids is of great importance in order to find the optimal dose regimen reducing the drug toxicity. Until now, CMS assay methods are based on the indirect determination after its hydrolysis to colistin (CS). Herein, the aim is to find the optimal conditions for the complete hydrolysis of CMS to CS. The reaction was studied at accelerated conditions: 40 °C, 50 °C, and 60 °C, and the results were evaluated by assessing the Arrhenius equation and computation employing the Tenua software. A validated analytical methodology based on ultra-performance liquid chromatography (UPLC) coupled to a hybrid quadrupole time of flight (QToF) instrument is developed for the simultaneous measurement of CMS and CS. The current methodology resulted in complete hydrolysis, in contrast with the previously reported one.
Untargeted Ultrahigh-Performance Liquid Chromatography-Hybrid Quadrupole-Orbitrap Mass Spectrometry (UHPLC-HRMS) Metabolomics Reveals Propolis Markers of Greek and Chinese Origin
Authors: Stavropoulou Maria-Ioanna , Termentzi Aikaterini , Kasiotis Konstantinos M. , Cheilari Antigoni , Stathopoulou Konstantina , Machera Kyriaki , Aligiannis Nektarios
Published: January 2021

Chemical composition of propolis depends on the plant source and thus on the geographic and climatic characteristics of the site of collection. The aim of this study was to investigate the chemical profile of Greek and Chinese propolis extracts from different regions and suggest similarities and differences between them. Untargeted ultrahigh-performance liquid chromatography coupled to hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-HRMS) method was developed and 22 and 23 propolis samples from Greece and China, respectively, were analyzed. The experimental data led to the observation that there is considerable variability in terms of quality of the distinctive propolis samples. Partial least squares - discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models were constructed and allowed the identification of significant features for sample discrimination, adding relevant information for the identification of class-determining metabolites. Chinese samples overexpressed compounds that are characteristic of the poplar type propolis, whereas Greek samples overexpress the latter and the diterpenes characteristic of the Mediterranean propolis type.
Fe2O3 Nanoparticles Doped with Gd: Phase Transformations as a Result of Thermal Annealing
Authors: Kozlovskiy Artem , Egizbek Kamila , Zdorovets Maxim V. , Kadyrzhanov Kayrat
Published: January 2021

The aim of this work is to study the effect of the phase composition of the synthesized Fe2O3-Gd2O3 nanoparticles on the efficiency of using magnetic hyperthermia as a basis for experiments. This class of structures is one of the most promising materials for biomedical applications and magnetic resonance imaging. In the course of the study, the dynamics of phase transformations of nanoparticles Fe2O3 → Fe2O3/GdFeO3 → GdFeO3 were established depending on the annealing temperature. It has been determined that the predominance of the GdFeO3 phase in the structure of nanoparticles leads to an increase in their size from 15 to 40 nm. However, during experiments to determine the resistance to degradation and corrosion, it was found that GdFeO3 nanoparticles have the highest corrosion resistance. During the hyperthermal tests, it was found that a change in the phase composition of nanoparticles, as well as their size, leads to an increase in the heating rate of nanoparticles, which can be further used for practical purposes.
Identification of the New In Vivo Metabolites of Ilaprazole in Rat Plasma after Oral Administration by LC-MS: In Silico Prediction of the H+/K+-ATPase Inhibitor
Authors: Zhang Guiqiu , Guo Kaijing , Wang Pengfei , Shan Yingbo , Ma Chen
Published: January 2021

Ilaprazole is a proton pump inhibitor used to treat digestive diseases. In this study, blood samples were collected after oral administration of ilaprazole and prepared by liquid–liquid extraction. The metabolites of ilaprazole were detected by liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and LC-MSn. A total of twelve in vivo metabolites were detected in rat plasma and six new metabolites of ilaprazole, including one reductive metabolite with sulfide (M3), two hydroxylated metabolites with sulfoxide (M7 and M8), and three oxidative metabolites with sulfone (M9, M11, and M12), were identified. The possible metabolic pathways of ilaprazole and the fragmentation behaviors of its metabolites were elucidated. The result of the in silico prediction indicates that all the new metabolites showed the potential ability to inhibit H+/K+-ATPase activity.
Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization
Authors: Anis Omer , Vinayaka Ajjampura C. , Shalev Nurit , Namdar Dvora , Nadarajan Stalin , Anil Seegehalli M. , Cohen Ofer , Belausov Eduard , Ramon Jacob , Mayzlish Gati Einav , Koltai Hinanit
Published: January 2021

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.
Tin, Titanium, Tantalum, Vanadium and Niobium Oxide Based Sensors to Detect Colorectal Cancer Exhalations in Blood Samples
Authors: Astolfi Michele , Rispoli Giorgio , Anania Gabriele , Artioli Elena , Nevoso Veronica , Zonta Giulia , Malagù Cesare
Published: January 2021

User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.
Lipolytic Postbiotic from Lactobacillus paracasei Manages Metabolic Syndrome in Albino Wistar Rats
Authors: Osman Ali , El-Gazzar Nashwa , Almanaa Taghreed N. , El-Hadary Abdalla , Sitohy Mahmoud
Published: January 2021

The current study investigates the capacity of a lipolytic Lactobacillus paracasei postbiotic as a possible regulator for lipid metabolism by targeting metabolic syndrome as a possibly safer anti-obesity and Anti-dyslipidemia agent replacing atorvastatin (ATOR) and other drugs with proven or suspected health hazards. The high DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS [2,2′-azino-bis (3-ethyl benzothiazoline-6-sulphonic acid)] scavenging activity and high activities of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) of the Lactobacillus paracasei postbiotic (cell-free extract), coupled with considerable lipolytic activity, may support its action against metabolic syndrome. Lactobacillus paracasei isolate was obtained from an Egyptian cheese sample, identified and used for preparing the postbiotic. The postbiotic was characterized and administered to high-fat diet (HFD) albino rats (100 and 200 mg kg−1) for nine weeks, as compared to atorvastatin (ATOR; 10 mg kg−1). The postbiotic could correct the disruption in lipid metabolism and antioxidant enzymes in HFD rats more effectively than ATOR. The two levels of the postbiotic (100 and 200 mg kg−1) reduced total serum lipids by 29% and 34% and serum triglyceride by 32–45% of the positive control level, compared to only 25% and 35% in ATOR’s case, respectively. Both ATOR and the postbiotic (200 mg kg−1) equally decreased total serum cholesterol by about 40% and 39%, while equally raising HDL levels by 28% and 30% of the positive control. The postbiotic counteracted HFD-induced body weight increases more effectively than ATOR without affecting liver and kidney functions or liver histopathology, at the optimal dose of each. The postbiotic is a safer substitute for ATOR in treating metabolic syndrome.
Characterization of a Novel Laccase LAC-Yang1 from White-Rot Fungus Pleurotus ostreatus Strain Yang1 with a Strong Ability to Degrade and Detoxify Chlorophenols
Authors: Liu Xinping , Deng Wei , Yang Yang
Published: January 2021

In this study, a laccase LAC-Yang1 was successfully purified from a white-rot fungus strain Pleurotus ostreatus strain yang1 with high laccase activity. The enzymatic properties of LAC-Yang1 and its ability to degrade and detoxify chlorophenols such as 2,6-dichlorophenol and 2,3,6-trichlorophenol were systematically studied. LAC-Yang1 showed a strong tolerance to extremely acidic conditions and strong stability under strong alkaline conditions (pH 9–12). LAC-Yang1 also exhibited a strong tolerance to different inhibitors (EDTA, SDS), metal ions (Mn2+, Cu2+, Mg2+, Na+, K+, Zn2+, Al3+, Co2+, and metal ion mixtures), and organic solvents (glycerol, propylene glycol). LAC-Yang1 showed good stability in the presence of Mg2+, Mn2+, glycerol, and ethylene glycol. Our results reveal the strong degradation ability of this laccase for high concentrations of chlorophenols (especially 2,6-dichlorophenol) and chlorophenol mixtures (2,6-dichlorophenol + 2,3,6-trichlorophenol). LAC-Yang1 displayed a strong tolerance toward a variety of metal ions (Na2+, Zn2+, Mn2+, Mg2+, K+ and metal ion mixtures) and organic solvents (glycerol, ethylene glycol) in its degradation of 2,6-dichlorophenol and 2,3,6-trichlorophenol. The phytotoxicity of 2,6-dichlorophenol treated by LAC-Yang1 was significantly reduced or eliminated. LAC-Yang1 demonstrated a good detoxification effect on 2,6-dichlorophenol while degrading this compound. In conclusion, LAC-Yang1 purified from Pleurotus ostreatus has great application value and potential in environmental biotechnology, especially the efficient degradation and detoxification of chlorophenols.
Molecular Docking Suggests the Targets of Anti-Mycobacterial Natural Products
Authors: Baptista Rafael , Bhowmick Sumana , Shen Jianying , Mur Luis A. J.
Published: January 2021

Tuberculosis (TB) is a major global threat, mostly due to the development of antibiotic-resistant forms of Mycobacterium tuberculosis, the causal agent of the disease. Driven by the pressing need for new anti-mycobacterial agents several natural products (NPs) have been shown to have in vitro activities against M. tuberculosis. The utility of any NP as a drug lead is augmented when the anti-mycobacterial target(s) is unknown. To suggest these, we used a molecular reverse docking approach to predict the interactions of 53 selected anti-mycobacterial NPs against known “druggable” mycobacterial targets ClpP1P2, DprE1, InhA, KasA, PanK, PknB and Pks13. The docking scores/binding free energies were predicted and calculated using AutoDock Vina along with physicochemical and structural properties of the NPs, using PaDEL descriptors. These were compared to the established inhibitor (control) drugs for each mycobacterial target. The specific interactions of the bisbenzylisoquinoline alkaloids 2-nortiliacorinine, tiliacorine and 13′-bromotiliacorinine against the targets PknB and DprE1 (−11.4, −10.9 and −9.8 kcal·mol−1; −12.7, −10.9 and −10.3 kcal·mol−1, respectively) and the lignan α-cubebin and Pks13 (−11.0 kcal·mol−1) had significantly superior docking scores compared to controls. Our approach can be used to suggest predicted targets for the NP to be validated experimentally, but these in silico steps are likely to facilitate drug optimization.
Unravelling the Allosteric Targeting of PHGDH at the ACT-Binding Domain with a Photoactivatable Diazirine Probe and Mass Spectrometry Experiments
Authors: Spillier Quentin , Ravez Séverine , Dochain Simon , Vertommen Didier , Thabault Léopold , Feron Olivier , Frédérick Raphaël
Published: January 2021

The serine biosynthetic pathway is a key element contributing to tumor proliferation. In recent years, targeting of phosphoglycerate dehydrogenase (PHGDH), the first enzyme of this pathway, intensified and revealed to be a promising strategy to develop new anticancer drugs. Among attractive PHGDH inhibitors are the α-ketothioamides. In previous work, we have demonstrated their efficacy in the inhibition of PHGDH in vitro and in cellulo. However, the precise site of action of this series, which would help the rational design of new inhibitors, remained undefined. In the present study, the detailed mechanism-of-action of a representative α-ketothioamide inhibitor is reported using several complementary experimental techniques. Strikingly, our work led to the identification of an allosteric site on PHGDH that can be targeted for drug development. Using mass spectrometry experiments and an original α-ketothioamide diazirine-based photoaffinity probe, we identified the 523Q-533F sequence on the ACT regulatory domain of PHGDH as the binding site of α-ketothioamides. Mutagenesis experiments further documented the specificity of our compound at this allosteric site. Our results thus pave the way for the development of new anticancer drugs using a completely novel mechanism-of-action.
Energy Storage and Electrocaloric Cooling Performance of Advanced Dielectrics
Authors: Zhang Yalong , Chen Jie , Dan Huiyu , Maraj Mudassar , Peng Biaolin , Sun Wenhong
Published: January 2021

Dielectric capacitors are widely used in pulse power systems, electric vehicles, aerospace, and defense technology as they are crucial for electronic components. Compact, lightweight, and diversified designs of electronic components are prerequisites for dielectric capacitors. Additionally, wide temperature stability and high energy storage density are equally important for dielectric materials. Ferroelectric materials, as special (spontaneously polarized) dielectric materials, show great potential in the field of pulse power capacitors having high dielectric breakdown strength, high polarization, low-temperature dependence and high energy storage density. The first part of this review briefly introduces dielectric materials and their energy storage performance. The second part elaborates performance characteristics of various ferroelectric materials in energy storage and refrigeration based on electrocaloric effect and briefly shed light on advantages and disadvantages of various common ferroelectric materials. Especially, we summarize the polarization effects of underlying substrates (such as GaN and Si) on the performance characteristics of ferroelectric materials. Finally, the review will be concluded with an outlook, discussing current challenges in the field of dielectric materials and prospective opportunities to assess their future progress.
The Role of Bioactive Phenolic Compounds on the Impact of Beer on Health
Authors: Ambra Roberto , Pastore Gianni , Lucchetti Sabrina
Published: January 2021

This review reports recent knowledge on the role of ingredients (barley, hop and yeasts), including genetic factors, on the final yield of phenolic compounds in beer, and how these molecules generally affect resulting beer attributes, focusing mainly on new attempts at the enrichment of beer phenols, with fruits or cereals other than barley. An entire section is dedicated to health-related effects, analyzing the degree up to which studies, investigating phenols-related health effects of beer, have appropriately considered the contribution of alcohol (pure or spirits) intake. For such purpose, we searched Scopus.com for any kind of experimental model (in vitro, animal, human observational or intervention) using beer and considering phenols. Overall, data reported so far support the existence of the somehow additive or synergistic effects of phenols and ethanol present in beer. However, findings are inconclusive and thus deserve further animal and human studies.
Antioxidant, Anti-Inflammatory and Antidiabetic Proprieties of LC-MS/MS Identified Polyphenols from Coriander Seeds
Authors: Mechchate Hamza , Es-safi Imane , Amaghnouje Amal , Boukhira Smahane , A. Alotaibi Amal , Al-zharani Mohammed , A. Nasr Fahd , M. Noman Omar , Conte Raffaele , Amal El Hamsas El Youbi , Bekkari Hicham , Bousta Dalila
Published: January 2021

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic mice were orally administered with PCS (25 and 50 mg/kg b.w.) for 28 days. Oral glucose tolerance (OGTT) was also evaluated along with the anti-inflammatory effect, assessed by measuring paw edema development induced with carrageenan in Wistar rat and the antioxidant activity assessed using two tests (β-carotene discoloration and DPPH). Treatment of diabetic mice with PCS for four weeks managed their high fasting blood glucose levels, improved their overall health, also revealed an excellent antihyperlipidemic activity. The OGTT result showed a potent antihyperglycemic activity, and following the anti-inflammatory and antioxidant effects, the PCS exhibited a perfect activity. LC-MS/MS result revealed the presence of 9 polyphenols. This modest work indicates that the PCS have an important antidiabetic, antihyperglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant effect that can be well established treatment of diabetes and its complications.
Virtual Screening of Natural Compounds as Potential PI3K-AKT1 Signaling Pathway Inhibitors and Experimental Validation
Authors: Dotolo Serena , Cervellera Carmen , Russo Maria , Russo Gian Luigi , Facchiano Angelo
Published: January 2021

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI3K/AKT pathway.
Effect of Substitution of Hydrogen Atoms in the Molecules of Anthrone and Anthraquinone
Authors: Szymańska Małgorzata , Majerz Irena
Published: January 2021

The geometry of anthrone and anthraquinone—natural substances of plant origin—was investigated under the substitution of hydrogen atoms in side aromatic ring and, for anthrone, also in the central ring. A significant influence of substitution on geometry expressed by the angle between the side rings was shown. The geometry changes are connected with the changes of electron density and aromaticity of the anthrone and anthraquinone rings. The flexibility of the investigated compounds was confirmed by comparison of the optimized molecules and the molecules in the crystal state where the packing forces can influence the molecular geometry.
Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro
Authors: Panahipour Layla , Husejnovic Selma , Nasirzade Jila , Semelmayer Stephan , Gruber Reinhard
Published: January 2021

Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently reported to decrease the expression of inhibitor of DNA-binding (ID) proteins, there is a rationale to assume that casein and whey can also provoke these responses in oral cells. To examine the TGF-β activity, gingival fibroblasts were exposed to reconstituted casein and whey powder from food supplement before the expression of TGF-β target genes were analyzed by reverse transcription-quantitative polymerase chain reaction. Immunoassays were performed for interleukin11 (IL11) in the cell culture supernatant and for TGF-β in the reconstituted casein and whey. We blocked TGF-β by neutralizing the antibody and the TGF-β receptor type I kinase with the inhibitor SB431542. We also showed smad3 phosphorylation and smad2/3 nuclear translocation by Western blot and immunostaining, respectively. Moreover, with reconstituted casein and whey powder, ID1 and ID3 expression analysis was evaluated in HSC2 human oral squamous carcinoma cells. We report here that casein and whey powder caused a robust increase of TGF-β target genes interleukin11 (IL11), NADPH oxidase 4 (NOX4) and proteoglycan4 (PRG4) in gingival fibroblasts that was blocked by SB431542 and the neutralizing antibody. Moreover, casein and whey powder increased the phosphorylation of smad3 and nuclear translocation of smad2/3. No changes of proliferation markers Ki67 and cyclinD1 were observed. Furthermore, reconstituted casein and whey powder decreased ID1 and ID3 expression in the HSC2 oral squamous carcinoma cells. These findings suggest that the processing of milk into casein and whey powder maintains the TGF-β activity and its capacity to regulate ID1 and ID3 genes in oral fibroblasts and oral squamous carcinoma cells, respectively. These data increase the scientific knowledge on the biological activity of casein and whey with a special emphasis on oral health.
Effects of Physical and Chemical Factors on the Structure of Gluten, Gliadins and Glutenins as Studied with Spectroscopic Methods
Authors: Kłosok Konrad , Welc Renata , Fornal Emilia , Nawrocka Agnieszka
Published: January 2021

This review presents applications of spectroscopic methods, infrared and Raman spectroscopies in the studies of the structure of gluten network and gluten proteins (gliadins and glutenins). Both methods provide complimentary information on the secondary and tertiary structure of the proteins including analysis of amide I and III bands, conformation of disulphide bridges, behaviour of tyrosine and tryptophan residues, and water populations. Changes in the gluten structure can be studied as an effect of dough mixing in different conditions (e.g., hydration level, temperature), dough freezing and frozen storage as well as addition of different compounds to the dough (e.g., dough improvers, dietary fibre preparations, polysaccharides and polyphenols). Additionally, effect of above mentioned factors can be determined in a common wheat dough, model dough (prepared from reconstituted flour containing only wheat starch and wheat gluten), gluten dough (lack of starch), and in gliadins and glutenins. The samples were studied in the hydrated state, in the form of powder, film or in solution. Analysis of the studies presented in this review indicates that an adequate amount of water is a critical factor affecting gluten structure.