bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolutions of the Jerk and Snap Vectors for a Quasi Curve in Euclidean 3-Space
Authors: Hamouda Ebrahem , Cesarano Clemente , Askar Sameh , Elsharkawy Ayman
Published: December 2021

This work aims at studying resolutions of the jerk and snap vectors of a point particle moving along a quasi curve in Euclidean 3-space E3. In particular, we obtain the resolution of the jerk and snap vectors along the quasi vectors and offer an alternative resolution of the jerk and snap vectors along the tangential direction and two special radial directions that lie in the osculating and rectifying planes. This alternative resolution for a quasi plane curve in Euclidean 3-space E3 is given as corollary. Moreover, our results are illustrated via some examples.
Prediction of Hydraulic Jumps on a Triangular Bed Roughness Using Numerical Modeling and Soft Computing Methods
Authors: Dasineh Mehdi , Ghaderi Amir , Bagherzadeh Mohammad , Ahmadi Mohammad , Kuriqi Alban
Published: December 2021

This study investigates the characteristics of free and submerged hydraulic jumps on the triangular bed roughness in various T/I ratios (i.e., height and distance of roughness) using CFD modeling techniques. The accuracy of numerical modeling outcomes was checked and compared using artificial intelligence methods, namely Support Vector Machines (SVM), Gene Expression Programming (GEP), and Random Forest (RF). The results of the FLOW-3D® model and experimental data showed that the overall mean value of relative error is 4.1%, which confirms the numerical model’s ability to predict the characteristics of the free and submerged jumps. The SVM model with a minimum of Root Mean Square Error (RMSE) and a maximum of correlation coefficient (R2), compared with GEP and RF models in the training and testing phases for predicting the sequent depth ratio (y2/y1), submerged depth ratio (y3/y1), tailwater depth ratio (y4/y1), length ratio of jumps (Lj/y2*) and energy dissipation (ΔE/E1), was recognized as the best model. Moreover, the best result for predicting the length ratio of free jumps (Ljf/y2*) in the optimal gamma is γ = 10 and the length ratio of submerged jumps (Ljs/y2*) is γ = 0.60. Based on sensitivity analysis, the Froude number has the greatest effect on predicting the (y3/y1) compared with submergence factors (SF) and T/I. By omitting this parameter, the prediction accuracy is significantly reduced. Finally, the relationships with good correlation coefficients for the mentioned parameters in free and submerged jumps were presented based on numerical results.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Kidney Transplantation
Authors: Binda Valentina , Favi Evaldo , Calatroni Marta , Moroni Gabriella
Published: December 2021

Due to complex comorbidity, high infectious complication rates, an elevated risk of relapsing for primary renal disease, as well as inferior recipient and allograft survivals, individuals with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) are often considered as poor transplant candidates. Although several aspects of recurrent and de novo AAVs remain unclear, recent evidence suggests that kidney transplantation (KT) represents the best option, which is also the case for this particular subgroup of patients. Special counselling and individualized approaches are strongly recommended at the time of enlistment and during the entire post-transplant follow-up. Current strategies include avoiding transplantation within one year of complete clinical remission and thoroughly assessing the recipient for early signs of renal or systemic vasculitis. The main clinical manifestations of allograft AAV are impaired kidney function, proteinuria, and hematuria with ANCA positivity in most cases. Mixed results have been obtained using high-dose steroids, mycophenolate mofetil, or cyclophosphamide. The aim of the present review was to summarize the available literature on AAVs in KT, particularly focusing on de novo pauci-immune glomerulonephritis.
Correlation between Laser-Ultrasound and Microstructural Properties of Laser Melting Deposited Ti6Al4V/B4C Composites
Authors: Xu Wanwei , Bai Xue , Sun Zhonggang , Meng Xin , Guo Zhongming
Published: December 2021

The presence of large microtextured clusters (MTC) composed of small α-phase crystallites with preferred crystallographic orientations in 3D printed near-α titanium alloys leads to poor mechanical and fatigue properties. It is therefore crucial to characterize the size of MTCs nondestructively. Ti6Al4V/B4C composite materials are manufactured using Laser Melting Deposition (LMD) technology by adding an amount of nano-sized B4C particles to the original Ti6Al4V powder. TiB and TiC reinforcements precipitating at grain boundaries stimulate the elongated α crystallites and coarse columnar MTCs to equiaxed transition, and microstructures composed of approximately equiaxed MTCs with different mean sizes of 11–50 μm are obtained. Theoretical models for scattering-induced attenuation and centroid frequency downshift of ultrasonic waves propagating in such a polycrystalline medium are presented. It is indicated that, the studied composite material has an extremely narrow crystallographic orientation distribution width, i.e., a strong degree of anisotropy in MTCs. Therefore, MTCs make a dominant contribution to the total scattering-induced attenuation and spectral centroid frequency downshift, while the contribution of fine α-phase crystallites is insignificant. Laser ultrasonic inspection is performed, and the correlation between laser-generated ultrasonic wave properties and microstructural properties of the Ti6Al4V/B4C composites is analyzed. Results have shown that the deviation between the experimentally measured ultrasonic velocity and the theoretical result determined by the Voigt-averaged velocity in each crystallite is no more than 2.23%, which is in good agreement with the degree of macroscopically anisotropy in the composite specimens. The ultrasonic velocity seems to be insensitive to the size of MTCs, while the spectral centroid frequency downshift is approximately linear to the mean size of MTCs with a goodness-of-fit (R2) up to 0.99. Actually, for a macroscopically untextured near-α titanium alloy with a relatively narrow crystallographic orientation distribution, the ultrasonic velocity is not correlated with the properties of MTCs, by contrast, the central frequency downshift is dominated by the size and morphology of MTCs, showing great potentials in grain size evaluation.
Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity
Authors: Lanzon Borja , Martin-Taboada Marina , Castro-Alves Victor , Vila-Bedmar Rocio , González de Pablos Ignacio , Duberg Daniel , Gomez Pilar , Rodriguez Elias , Orešič Matej , Hyötyläinen Tuulia , Morales Enrique , Ruperez Francisco J. , Medina-Gomez Gema
Published: December 2021

Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity.
Species- and Caste-Specific Gut Metabolomes in Fungus-Farming Termites
Authors: Vidkjær Nanna Hjort , Schmidt Suzanne , Hu Haofu , Bodawatta Kasun H. , Beemelmanns Christine , Poulsen Michael
Published: December 2021

Fungus-farming termites host gut microbial communities that contribute to the pre-digestion of plant biomass for manuring the fungal mutualist, and potentially to the production of defensive compounds that suppress antagonists. Termite colonies are characterized by complex division of labor and differences in diet between termite size (minor and major) and morphological (worker and soldier) castes, and this extends to the composition of their gut microbial communities. We hypothesized that gut metabolomes should mirror these differences and tested this through untargeted LC-MS/MS analyses of three South African species of fungus-farming termites. We found distinct metabolomes between species and across castes, especially between soldiers and workers. Primary metabolites dominate the metabolomes and the high number of overlapping features with the mutualistic fungus and plant material show distinct impacts of diet and the environment. The identification of a few bioactive compounds of likely microbial origin underlines the potential for compound discovery among the many unannotated features. Our untargeted approach provides a first glimpse into the complex gut metabolomes and our dereplication suggests the presence of bioactive compounds with potential defensive roles to be targeted in future studies.
Cross-Talk between Probiotic Nissle 1917 and Human Colonic Epithelium Affects the Metabolite Composition and Demonstrates Host Antibacterial Effect
Authors: Dokladny Karol , Crane John K. , Kassicieh Alex J. , Kaper James B. , Kovbasnjuk Olga
Published: December 2021

Colonic epithelium–commensal interactions play a very important role in human health and disease development. Colonic mucus serves as an ecologic niche for a myriad of commensals and provides a physical barrier between the epithelium and luminal content, suggesting that communication between the host and microbes occurs mainly by soluble factors. However, the composition of epithelia-derived metabolites and how the commensal flora influences them is less characterized. Here, we used mucus-producing human adult stem cell-derived colonoid monolayers exposed apically to probiotic E. coli strain Nissle 1917 to characterize the host–microbial communication via small molecules. We measured the metabolites in the media from host and bacterial monocultures and from bacteria-colonoid co-cultures. We found that colonoids secrete amino acids, organic acids, nucleosides, and polyamines, apically and basolaterally. The metabolites from host-bacteria co-cultures markedly differ from those of host cells grown alone or bacteria grown alone. Nissle 1917 affects the composition of apical and basolateral metabolites. Importantly, spermine, secreted apically by colonoids, shows antibacterial properties, and inhibits the growth of several bacterial strains. Our data demonstrate the existence of a cross-talk between luminal bacteria and human intestinal epithelium via metabolites, which might affect the numbers of physiologic processes including the composition of commensal flora via bactericidal effects.
Theoretical Thermal-Mechanical Modelling and Experimental Validation of a Three-Dimensional (3D) Electrothermal Microgripper with Three Fingers
Authors: Si Guoning , Sun Liangying , Zhang Zhuo , Zhang Xuping
Published: December 2021

This paper presents the theoretical thermal-mechanical modeling and parameter analyses of a novel three-dimensional (3D) electrothermal microgripper with three fingers. Each finger of the microgripper is composed of a bi-directional Z-shaped electrothermal actuator and a 3D U-shaped electrothermal actuator. The bi-directional Z-shaped electrothermal actuator provides the rectilinear motion in two directions. The novel 3D U-shaped electrothermal actuator offers motion with two degrees of freedom (DOFs) in the plane perpendicular to the movement of the Z-shaped actuator. As a result, each finger possesses 3D mobilities with three DOFs. Each beam of the actuators is heated externally with polyimide films. In this work, the static theoretical thermal-mechanical model of the 3D U-shaped electrothermal actuator is established. Finite-element analyses and experimental tests are conducted to verify and validate the model. With this model, parameter analyses are carried out to provide insight and guidance on further improving the 3D U-shaped actuator. Furthermore, a group of micro-manipulation experiments are conducted to demonstrate the flexibility and versality of the 3D microgripper on manipulate different types of small/micro-objects.
Isolation of Lactococcus lactis from Whole Crop Rice and Determining Its Probiotic and Antimicrobial Properties towards Gastrointestinal Associated Bacteria
Authors: Soundharrajan Ilavenil , Yoon Yong Hee , Muthusamy Karnan , Jung Jeong-Sung , Lee Hyun Jeong , Han Ouk-Kyu , Choi Ki Choon
Published: December 2021

Antimicrobial resistance is an emerging condition that increases the risk of spreading and prolonging infectious diseases globally. Therefore, a new alternative strategy for antibiotics is required urgently to control pathogens spreading. Probiotics are considered as an alternative for antibiotics that inhibit pathogens. In the present study, potent lactic acid bacteria (LAB) were isolated and screened for their probiotic characteristics and antagonistic activity against intestinal pathogens by agar well diffusion, Time and Dose-dependent killing assay, minimum inhibitor, and minimum bactericidal concentration (MIC/MBC), and co-culture methods. The Lactococcus lactis RWP-3 and RWP-7 fermented the different carbohydrate substrates and produced different extracellular enzymes. Both isolates showed significant tolerant capability in the gastric, duodenal, and intestinal juices. In addition, RWP-3 and RWP-7 had hydrophobicity and aggregation properties in a time-dependent manner. Furthermore, the cell-free secondary metabolites (CFS) of RWP-3 and RWP-7 showed strong antibacterial activity against Escherichia coli,Staphylococcus aureus, Pseudomonas aeruginosa and Enterococcus faecalis. A co-culture study revealed that the RWP-3 and RWP-7 strongly compete with pathogen growths. RWP-3 and RWP-7 showed strong antagonistic activities against tested pathogens with significant probiotic characteristics, suggesting that these strains obtained could be used as an alternative strategy for the antibiotic to control infectious pathogens.
Mobile Colistin Resistance Genetic Determinants of Non-Typhoid Salmonella enterica Isolates from Russia
Authors: Kuleshov Konstantin V. , Pavlova Anastasia S. , Shedko Elizaveta D. , Mikhaylova Yulia V. , Margos Gabriele , Hepner Sabrina , Chebotar Igor V. , Korneenko Elena V. , Podkolzin Alexander T. , Akimkin Vasiliy G.
Published: December 2021

Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently poses a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carrying mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n = 586). mcr-1 genes were detected using a previously developed qPCR assay, and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates, including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans, carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene-carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological backgrounds.
Water in the Alluaudite Type-Compounds: Synthesis, Crystal Structure and Magnetic Properties of Co3(AsO4)0.5+x(HAsO4)2−x(H2AsO4)0.5+x[(H,□)0.5(H2O,H3O)0.5]2x+
Authors: Đorđević Tamara , Karanović Ljiljana , Jagodič Marko , Jagličić Zvonko
Published: December 2021

In this study, a new cobalt arsenate belonging to the alluaudite supergroup compounds with the general formula of Co3(AsO4)0.5+x(HAsO4)2−x(H2AsO4)0.5+x[(H,□)0.5(H2O,H3O)0.5]2x+ (denoted as CoAsAllu) was synthesized under hydrothermal conditions. Its crystal structure was determined by a room-temperature single-crystal X-ray diffraction analysis: space group C2/c, a = 11.6978(8), b = 12.5713(7), c = 6.7705(5) Å, β = 113.255(5)°, V = 914.76(11) Å3, Z = 2 for As6H8Co6O25. It represents a new member of alluaudite-like protonated arsenates and the first alluaudite-like phase showing both protonation of the tetrahedral site and presence of the H2O molecules in the channels. In the asymmetric unit of CoAsAllu, one of the two Co, one of the two As and one of the seven O atoms lie at 4e special positions (site symmetry 2). The crystal structure consists of the infinite edge-shared CoO6 octahedra chains, running parallel to the [101¯] direction. The curved chains are interconnected by [(As1O4)0.5(H2As1O4)0.5]2− and [HAs2O4]2− tetrahedra forming a heteropolyhedral 3D open framework with two types of parallel channels. Both channels run along the c-axis and are located at the positions (1/2, 0, z) and (0, 0, z), respectively. The H2 and H4 hydrogen atoms of O2H2 and O4H4 hydroxyl groups are situated in channel 1, while the uncoordinated water molecule H2O7 at half-occupied 4e special positions and hydrogen atoms of O6H6 hydroxyl group were found in channel 2. The results of the magnetic investigations confirm the quasi one-dimensional structure of divalent cobalt ions. They are antiferromagnetically coupled with the intrachain interaction parameter of J ≈ −8 cm−1 and interchain parameter of J’ ≈ −2 cm−1 that become effective below the Néel temperature of 3.4 K.
Main Factors Involved in Thyroid Hormone Action
Authors: Tedeschi Lorena , Vassalle Cristina , Iervasi Giorgio , Sabatino Laura
Published: December 2021

The thyroid hormone receptors are the mediators of a multitude of actions by the thyroid hormones in cells. Most thyroid hormone activities require interaction with nuclear receptors to bind DNA and regulate the expression of target genes. In addition to genomic regulation, thyroid hormones function via activation of specific cytosolic pathways, bypassing interaction with nuclear DNA. In the present work, we reviewed the most recent literature on the characteristics and roles of different factors involved in thyroid hormone function in particular, we discuss the genomic activity of thyroid hormone receptors in the nucleus and the functions of different thyroid hormone receptor isoforms in the cytosol. Furthermore, we describe the integrin αvβ3-mediated thyroid hormone signaling pathway and its rapid nongenomic action in the cell. We furthermore reviewed the thyroid hormone transporters enabling the uptake of thyroid hormones in the cell, and we also include a paragraph on the proteins that mediate thyroid receptors’ shuttling from the nucleus to the cytosol.
Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies
Authors: Narwane Manmath , Dorairaj Dorothy Priyanka , Chang Yu-Lun , Karvembu Ramasamy , Huang Yu-Han , Chang Hsueh-Wei , Hsu Sodio C. N.
Published: December 2021

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tppy) ligand (1–3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TppyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TppyZn(II) chemistry. In complex [TppyZn(H2O)][BF4] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TppyZnN3] (3). The complexes (1–3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 104–105 M−1. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1–3) exhibited good IC50 values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.
The Cyclobutanocucurbit[5–8]uril Family: Electronegative Cavities in Contrast to Classical Cucurbituril while the Electropositive Outer Surface Acts as a Crystal Packing Driver
Authors: Chen Minghua , Lv Naixia , Zhao Weiwei , Day Anthony I.
Published: December 2021

The structural parameters for the cyclobutanoQ[5–8] family were determined through single crystal X-ray diffraction. It was found that the electropositive cyclobutano methylene protons (CH2) are important in forming interlinking crystal packing arrangements driven by the dipole–dipole interactions between these protons and the portal carbonyl O of a near neighbor. This type of interaction was observed across the whole family. Electrostatic potential maps also confirmed the electropositive nature of the cyclobutano CH2 but, more importantly, it was established that the cavities are electronegative in contrast to classical Q[5–8], which are near neutral.
Anharmonic Vibrational Frequencies of Water Borane and Associated Molecules
Authors: Westbrook Brent R. , Fortenberry Ryan C.
Published: December 2021

Water borane (BH3OH2) and borinic acid (BH2OH) have been proposed as intermediates along the pathway of hydrogen generation from simple reactants: water and borane. However, the vibrational spectra for neither water borane nor borinic acid has been investigaged experimentally due to the difficulty of isolating them in the gas phase, making accurate quantum chemical predictions for such properties the most viable means of their determination. This work presents theoretical predictions of the full rotational and fundamental vibrational spectra of these two potentially application-rich molecules using quartic force fields at the CCSD(T)-F12b/cc-pCVTZ-F12 level with additional corrections included for the effects of scalar relativity. This computational scheme is further benchmarked against the available gas-phase experimental data for the related borane and HBO molecules. The differences are found to be within 3 cm−1 for the fundamental vibrational frequencies and as close as 15 MHz in the B0 and C0 principal rotational constants. Both BH2OH and BH3OH2 have multiple vibrational modes with intensities greater than 100 km mol−1, namely ν2 and ν4 in BH2OH, and ν1, ν3, ν4, ν9, and ν13 in BH3OH2. Finally, BH3OH2 has a large dipole moment of 4.24 D, which should enable it to be observable by rotational spectroscopy, as well.
Ultrasonication Improves Solid Phase Synthesis of Peptides Specific for Fibroblast Growth Factor Receptor and for the Protein-Protein Interface RANK-TRAF6
Authors: Silva Rúben D. M. , Franco Machado João , Gonçalves Kyle , Lucas Francisco M. , Batista Salete , Melo Rita , Morais Tânia S. , Correia João D. G.
Published: December 2021

Considering our interest in the use of peptides as potential target-specific drugs or as delivery vectors of metallodrugs for various biomedical applications, it is crucial to explore improved synthetic methodologies to accomplish the highest peptide crude purity in the shortest time possible. Therefore, we compared “classical” fluorenylmethoxycarbonyl (Fmoc)-solid phase peptide synthesis (SPPS) with ultrasound(US)-assisted SPPS based on the preparation of three peptides, namely the fibroblast growth factor receptor 3(FGFR3)-specific peptide Pep1 (VSPPLTLGQLLS-NH2) and the novel peptides Pep2 (RQMATADEA-NH2) and Pep3 (AAVALLPAVLLALLAPRQMATADEA-NH2), which are being developed aimed at interfering with the intracellular protein-protein interaction(PPI) RANK-TRAF6. Our results demonstrated that US-assisted SPPS led to a 14-fold (Pep1) and 4-fold time reduction (Pep2) in peptide assembly compared to the “classical” method. Interestingly, US-assisted SPPS yielded Pep1 in higher purity (82%) than the “classical” SPPS (73%). The significant time reduction combined with high crude peptide purity attained prompted use to apply US-assisted SPPS to the large peptide Pep3, which displays a high number of hydrophobic amino acids and homooligo-sequences. Remarkably, the synthesis of this 25-mer peptide was attained during a “working day” (347 min) in moderate purity (approx. 49%). In conclusion, we have reinforced the importance of using US-SPPS towards facilitating the production of peptides in shorter time with increased efficacy in moderate to high crude purity. This is of special importance for long peptides such as the case of Pep3.
The Anthelmintic Quassinoids Ailanthone and Bruceine a Induce Infertility in the Model Organism Caenorhabditis elegans by an Apoptosis-like Mechanism Induced in Gonadal and Spermathecal Tissues
Authors: Knetzger Nicola , Bachtin Viktoria , Lehmann Susanne , Hensel Andreas , Liebau Eva , Herrmann Fabian
Published: December 2021

In continuation of the search for new anthelmintic natural products, the study at hand investigated the nematicidal effects of the two naturally occurring quassinoids ailanthone and bruceine A against the reproductive system of the model nematode Caenorhabditis elegans to pinpoint their anthelmintic mode of action by the application of various microscopic techniques. Differential Interference Contrast (DIC) and the epifluorescence microscopy experiments used in the presented study indicated the genotoxic effects of the tested quassinoids (c ailanthone = 50 µM, c bruceine A = 100 µM) against the nuclei of the investigated gonadal and spermathecal tissues, leaving other morphological key features such as enterocytes or body wall muscle cells unimpaired. In order to gain nanoscopic insight into the morphology of the gonads as well as the considerably smaller spermathecae of C. elegans, an innovative protocol of polyethylene glycol embedding, ultra-sectioning, acridine orange staining, tissue identification by epifluorescence, and subsequent AFM-based ultrastructural data acquisition was applied. This sequence allowed the facile and fast assessment of the impact of quassinoid treatment not only on the gonadal but also on the considerably smaller spermathecal tissues of C. elegans. These first-time ultrastructural investigations on C. elegans gonads and spermathecae by AFM led to the identification of specific quassinoid-induced alterations to the nuclei of the reproductive tissues (e.g., highly condensed chromatin, impaired nuclear membrane morphology, as well as altered nucleolus morphology), altogether implying an apoptosis-like effect of ailanthone and bruceine A on the reproductive tissues of C. elegans.
The Mineral Composition of Date Palm Fruits (Phoenix dactylifera L.) under Low to High Salinity Irrigation
Authors: Dghaim Rania , Hammami Zied , Al Ghali Rola , Smail Linda , Haroun Dalia
Published: December 2021

Adaptability to salinity varies between different varieties of date palm trees. This research aims to explore the long-term impact of different salinity irrigation levels on the mineral content of 13 date palm varieties grown in the United Arab Emirates (UAE). Date varieties were grown using three irrigation water salinity levels of 5, 10 and 15 dS m−1. The mineral composition (B, Ca, Cu, Fe, K, Mg, Na, P and Zn) of date palm fruits was determined using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). High salinity levels showed no effect on the mineral content of Ajwat AlMadinah, Naghal, Barhi, Shagri, Abu Maan, Jabri, Sukkari and Rothan varieties. All date varieties remained good sources of dietary potassium, magnesium, manganese and boron even at high salinity levels. Increased salinity had no effect on the percent Daily Value (%DV) categories of most of the analyzed minerals. While no genotypes showed a general adaptation to different saline environments, Barhi, Ajwat Al Madinah, Khinizi, Maktoumi and Shagri varieties were more stable towards salinity variation. In the UAE, the genotype x saline-environment interaction was found to be high which makes it impossible to attribute the variation in mineral content to a single varietal or salinity effect.
5-Dodecanolide, a Compound Isolated from Pig Lard, Presents Powerful Anti-Inflammatory Properties
Authors: Capó Xavier , Martorell Miquel , Tur Josep A. , Sureda Antoni , Pons Antoni
Published: December 2021

Background: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. Methods: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). Results: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. Conclusions: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.
Effect of S–Se Bioisosteric Exchange on Affinity and Intrinsic Efficacy of Novel N-acylhydrazone Derivatives at the Adenosine A2A Receptor
Authors: Pedreira Júlia Galvez Bulhões , Silva Rafaela Ribeiro , Noël François G. , Barreiro Eliezer J.
Published: December 2021

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3–8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp2 of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A2A receptor (A2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1–8). However, the N-methylated compounds (2, 6–8) presented a weak partial agonist profile at A2AR, contrary to the non-methylated counterparts (1, 3–5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.
An Efficient Approach to 2-CF3-Indoles Based on ortho-Nitrobenzaldehydes
Authors: Muzalevskiy Vasiliy M. , Sizova Zoia A. , Abaev Vladimir T. , Nenajdenko Valentine G.
Published: December 2021

The catalytic olefination reaction of 2-nitrobenzaldehydes with CF3CCl3 afforded stereoselectively trifluoromethylated ortho-nitrostyrenes in up to 88% yield. The reaction of these alkenes with pyrrolidine permits preparation of α-CF3-β-(2-nitroaryl) enamines. Subsequent one pot reduction of nitro-group by Fe-AcOH-H2O system initiated intramolecular cyclization to afford 2-CF3-indoles. Target products can be prepared in up to 85% yields. Broad synthetic scope of the reaction was shown as well as some followed up transformations of 2- CF3-indole.
Hydrothermal Synthesis of Silicoaluminophosphate with AEL Structure Using a Residue of Fluorescent Lamps as Starting Material
Authors: Lima Gidiângela C. C. S. , Mello Mariele I. S. , Bieseki Lindiane , Araujo Antonio S. , Pergher Sibele B. C.
Published: December 2021

Silicoaluminophosphate molecular sieves of SAPO-11 type (AEL structure) were synthesized by the hydrothermal method, from the residue of a fluorescent lamp as a source or Si, Al, and P in the presence of water and di-propyamine (DPA) as an organic template. To adjust the P2O5/SiO2 and Si/Al and ratios, specific amounts of silica, alumina, or alumina hydroxide and orthophosphoric acid were added to obtain a gel with molar chemical composition 1.0 Al2O3:1.0 P2O5:1.2 DPA:0.3 SiO2:120 H2O. The syntheses were carried out at a temperature of 473 K at crystallization times of 24, 48, and 72 h. The fluorescent lamp residue and the obtained samples were characterized by X-ray fluorescence, X-ray diffraction, scanning electron microscopy, and BET surface area analysis using nitrogen adsorption isotherms. The presence of fluorapatite was detected as the main crystalline phase in the residue, jointly with considered amounts of silica, alumina, and phosphorus in oxide forms. The SAPO-11 prepared using aluminum hydroxide as Al source, P2O5/SiO2 molar ratio of 3.6 and Si/Al ratio of 0.14, at crystallization time of 72 h, achieves a yield of 75% with a surface area of 113 m2/g, showing that the residue from a fluorescent lamp is an alternative source for development of new materials based on Si, Al, and P.
Optimized Liquid-Phase Exfoliation of Magnetic van der Waals Heterostructures: Towards the Single Layer and Deterministic Fabrication of Devices
Authors: Martín-Pérez Lucía , Burzurí Enrique
Published: December 2021

Van der Waals magnetic materials are promising candidates for spintronics and testbeds for exotic magnetic phenomena in low dimensions. The two-dimensional (2D) limit in these materials is typically reached by mechanically breaking the van der Waals interactions between layers. Alternative approaches to producing large amounts of flakes rely on wet methods such as liquid-phase exfoliation (LPE). Here, we report an optimized route for obtaining monolayers of magnetic cylindrite by LPE. We show that the selection of exfoliation times is the determining factor in producing a statistically significant amount of monolayers while keeping relatively big flake areas (~1 µm2). We show that the cylindrite lattice is preserved in the flakes after LPE. To study the electron transport properties, we have fabricated field-effect transistors based on LPE cylindrite. Flakes are deterministically positioned between nanoscale electrodes by dielectrophoresis. We show that dielectrophoresis can selectively move the larger flakes into the devices. Cylindrite nanoscale flakes present a p-doped semiconducting behaviour, in agreement with the mechanically exfoliated counterparts. Alternating current (AC) admittance spectroscopy sheds light on the role played by potential barriers between different flakes in terms of electron transport properties. The present large-scale exfoliation and device fabrication strategy can be extrapolated to other families of magnetic materials.
Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer
Authors: Lewandowska Paulina , Szczuka Izabela , Bednarz-Misa Iwona , Szczęśniak-Sięga Berenika M. , Neubauer Katarzyna , Mierzchała-Pasierb Magdalena , Zawadzki Marek , Witkiewicz Wojciech , Krzystek-Korpacka Małgorzata
Published: December 2021

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.
A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors
Authors: El-Gamal Mohammed I. , Mewafi Nada H. , Abdelmotteleb Nada E. , Emara Minnatullah A. , Tarazi Hamadeh , Sbenati Rawan M. , Madkour Moustafa M. , Zaraei Seyed-Omar , Shahin Afnan I. , Anbar Hanan S.
Published: December 2021

HER4 is a receptor tyrosine kinase that is required for the evolution of normal body systems such as cardiovascular, nervous, and endocrine systems, especially the mammary glands. It is activated through ligand binding and activates MAPKs and PI3K/AKT pathways. HER4 is commonly expressed in many human tissues, both adult and fetal. It is important to understand the role of HER4 in the treatment of many disorders. Many studies were also conducted on the role of HER4 in tumors and its tumor suppressor function. Mostly, overexpression of HER4 kinase results in cancer development. In the present article, we reviewed the structure, location, ligands, physiological functions of HER4, and its relationship to different cancer types. HER4 inhibitors reported mainly from 2016 to the present were reviewed as well.
On the Synergism of Biogenic Gold Nanoparticles and Hydroxyaluminum Phthalocyanines in the Photoeradication of Staphylococcus aureus
Authors: Maliszewska Irena
Published: December 2021

Due to the unusual properties of gold nanoparticles, these structures are widely used in medicine and biology. This paper describes for the first time the synthesis of colloidal gold nanoparticles by the cell-free filtrate obtained from the Coriolus versicolor biomass and the use of these biogenic nanostructures to increase the photosensitizing efficiency of di- (AlPcS2) and tetrasulfonated (AlPcS4) hydroxyaluminum phthalocyanines in antibacterial photodynamic therapy. The obtained monodisperse particles were extremely stable, and this remarkable stability was due to the presence of phosphoprotein as a capping agent. The studied gold nanoparticles had a spherical shape, were uniformly distributed, and were characterized by a single plasmon band at wavelength of 514–517 nm. Almost 60% of the gold particles were found to be in the range of 13 to 15 nm. In accordance with the regulations of the American Microbiological Society, indicating that any antimicrobial technique must kill at least 3 log CFU (99.9%) to be accepted as “antimicrobial”, this mortality of Staphylococcus aureus was shown to be achieved in the presence of AlPcS4 + AuNPs mixture and 4.8 J cm−2 light dose compared to AlPcS4 alone, which required a light dose of 24 J cm−2. The best effect of increasing the effectiveness of combating this pathogen was observed in the case of AlPcS2 + AuNPs as a photosensitizing mixture. The light dose of 24 J cm−2 caused a lethal effect of the studied coccus in the planktonic culture.
E/Z Molecular Photoswitches Activated by Two-Photon Absorption: Comparison between Different Families
Authors: Marazzi Marco , García-Iriepa Cristina , Benitez-Martin Carlos , Najera Francisco , Monari Antonio , Sampedro Diego
Published: December 2021

Nonlinear optical techniques as two-photon absorption (TPA) have raised relevant interest within the last years due to the capability to excite chromophores with photons of wavelength equal to only half of the corresponding one-photon absorption energy. At the same time, its probability being proportional to the square of the light source intensity, it allows a better spatial control of the light-induced phenomenon. Although a consistent number of experimental studies focus on increasing the TPA cross section, very few of them are devoted to the study of photochemical phenomena induced by TPA. Here, we show a design strategy to find suitable E/Z photoswitches that can be activated by TPA. A theoretical approach is followed to predict the TPA cross sections related to different excited states of various photoswitches’ families, finally concluding that protonated Schiff-bases (retinal)-like photoswitches outperform compared to the others. The donor-acceptor substitution effect is therefore rationalized for the successful TPA activatable photoswitch, in order to maximize its properties, finally also forecasting a possible application in optogenetics. Some experimental measurements are also carried out to support our conclusions.
Biological Investigation of Amaryllidaceae Alkaloid Extracts from the Bulbs of Pancratium trianthum Collected in the Senegalese Flora
Authors: Ka Seydou , Mérindol Natacha , Seck Insa , Ricard Simon , Diop Abdoulaye , Boye Cheikh Saad Bouh , Landelouci Karima , Daoust Benoit , Berthoux Lionel , Pépin Geneviève , Seck Matar , Desgagné-Penix Isabel
Published: December 2021

Amaryllidaceae plants are rich in alkaloids with biological properties. Pancratium trianthum is an Amaryllidaceae species widely used in African folk medicine to treat several diseases such as central nervous system disorders, tumors, and microbial infections, and it is used to heal wounds. The current investigation explored the biological properties of alkaloid extracts from bulbs of P. trianthum collected in the Senegalese flora. Alkaloid extracts were analyzed and identified by chromatography and mass spectrometry. Alkaloid extracts from P. trianthum displayed pleiotropic biological properties. Cytotoxic activity of the extracts was determined on hepatocarcinoma Huh7 cells and on acute monocytic leukemia THP-1 cells, while agar diffusion and microdilution assays were used to evaluate antibacterial activity. Antiviral activity was measured by infection of extract-treated cells with dengue virus (DENVGFP) and human immunodeficiency virus-1 (HIV-1GFP) reporter vectors. Cytotoxicity and viral inhibition were the most striking of P. trianthum’s extract activities. Importantly, non-cytotoxic concentrations were highly effective in completely preventing DENVGFP replication and in reducing pseudotyped HIV-1GFP infection levels. Our results show that P. trianthum is a rich source of molecules for the potential discovery of new treatments against various diseases. Herein, we provide scientific evidence to rationalize the traditional uses of P. trianthum for wound treatment as an anti-dermatosis and antiseptic agent.
Swelling Effects on the Conductivity of Graphene/PSS/PAH Composites
Authors: Zhao Tianbao , Yang Ruyi , Yang Zhi
Published: December 2021

Graphene/poly-(sodium-4-styrene sulfonate)(PSS)/poly-(allylamine hydrochloride) (PAH) composite is a frequently adopted system for fabricating polyelectrolyte multilayer films. Swelling is the bottleneck limiting its applications, and its effects on the conductivity is still controversial. Herein, we report successful swelling of a graphene/PSS/PAH composite in a vapor atmosphere, and the relation with the mass fraction of water is uncovered. The composite was prepared via a layer-by-layer assembly technique and systematically characterized. The results indicated that the average thickness for each bilayer was about 0.95 nm. The hardness and modulus were 2.5 ± 0.2 and 68 ± 5 GPa, respectively, and both were independent of thickness. The sheet resistance decreased slightly with the prolongation of immersion time, but was distinct from that of the water mass fraction. It reduced from 2.44 × 105 to 2.34 × 105 ohm/sq, and the change accelerated as the water mass fraction rose, especially when it was larger than 5%. This could be attributing to the lubrication effect of the water molecules, which sped up the migration of charged groups in the polyelectrolytes. Moreover, molecular dynamics simulations confirmed that a microphase separation occurred when the fraction reached an extreme value owing to the dominated interaction between PSS and PAH. These results provide support for the structural stability of this composite material and its applications in devices.