bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a Metabolite Extraction Method to Study the Metabolome of Blastocystis Using NMR
Authors: Newton Jamie M. , Betts Emma L. , Yiangou Lyto , Ortega Roldan Jose , Tsaousis Anastasios D. , Thompson Gary S.
Published: May 2021

Blastocystis is an opportunistic parasite commonly found in the intestines of humans and other animals. Despite its high prevalence, knowledge regarding Blastocystis biology within and outside the host is limited. Analysis of the metabolites produced by this anaerobe could provide insights that can help map its metabolism and determine its role in both health and disease. Due to its controversial pathogenicity, these metabolites could define its deterministic role in microbiome’s “health” and/or subsequently resolve Blastocystis’ potential impact in gastrointestinal health. A common method for elucidating the presence of these metabolites is through 1H nuclear magnetic resonance (NMR). However, there are currently no described benchmarked methods available to extract metabolites from Blastocystis for 1H NMR analysis. Herein, several extraction solvents, lysis methods and incubation temperatures were compared for their usefulness as an extraction protocol for this protozoan. Following extraction, the samples were freeze-dried, re-solubilized and analysed with 1H NMR. The results demonstrate that carrying out the procedure at room temperature using methanol as an extraction solvent and bead bashing as a lysis technique provides a consistent, reproducible and efficient method to extract metabolites from Blastocystis for NMR.
In Search of Factors Determining Activity of Co3O4 Nanoparticles Dispersed in Partially Exfoliated Montmorillonite Structure
Authors: Rokicińska Anna , Berniak Tomasz , Drozdek Marek , Kuśtrowski Piotr
Published: May 2021

The paper discusses a formation of Mt–PAA composite containing a natural montmorillonite structure partially exfoliated by poly(acrylic acid) introduced through intercalation polymerization of acrylic acid. Mt–PAA was subsequently modified by controlled adsorption of Co2+ ions. The presence of aluminosilicate packets (clay) and carboxyl groups (hydrogel) led to the deposition of significant amounts of Co2+ ions, which after calcination formed the Co3O4 spinel particles. The conditions of the Co2+ ions’ deposition (pH, volume and concentration of Co(NO3)2 solution, as well as a type of pH-controlling agent) were widely varied. Physicochemical characterization of the prepared materials (including X-ray fluorescence (XRF), X-ray powder diffraction (XRD), low-temperature nitrogen adsorption, X-ray photoelectron spectroscopy (XPS) and temperature-programmed reduction (H2-TPR)) revealed that the modification conditions strongly influenced the content as well as the distribution of the Co3O4 active phase, tuning its reducibility. The latter parameter was, in turn, very important from the point of view of catalytic activity in the combustion of aromatic volatile organic compounds (VOCs) following the Mars–van Krevelen mechanism.
Electrostatic Potential Topology for Probing Molecular Structure, Bonding and Reactivity
Authors: Gadre Shridhar R. , Suresh Cherumuttathu H. , Mohan Neetha
Published: May 2021

Following the pioneering investigations of Bader on the topology of molecular electron density, the topology analysis of its sister field viz. molecular electrostatic potential (MESP) was taken up by the authors’ groups. Through these studies, MESP topology emerged as a powerful tool for exploring molecular bonding and reactivity patterns. The MESP topology features are mapped in terms of its critical points (CPs), such as bond critical points (BCPs), while the minima identify electron-rich locations, such as lone pairs and π-bonds. The gradient paths of MESP vividly bring out the atoms-in-molecule picture of neutral molecules and anions. The MESP-based characterization of a molecule in terms of electron-rich and -deficient regions provides a robust prediction about its interaction with other molecules. This leads to a clear picture of molecular aggregation, hydrogen bonding, lone pair–π interactions, π-conjugation, aromaticity and reaction mechanisms. This review summarizes the contributions of the authors’ groups over the last three decades and those of the other active groups towards understanding chemical bonding, molecular recognition, and reactivity through topology analysis of MESP.
Molecular Dynamics Scoring of Protein–Peptide Models Derived from Coarse-Grained Docking
Authors: Zalewski Mateusz , Kmiecik Sebastian , Koliński Michał
Published: May 2021

One of the major challenges in the computational prediction of protein–peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein–peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor–ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein–peptide complexes show that the proposed MD-based scoring approach can be used to identify protein–peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures.
Effects of Charge Compensation on Colossal Permittivity and Electrical Properties of Grain Boundary of CaCu3Ti4O12 Ceramics Substituted by Al3+ and Ta5+/Nb5+
Authors: Boonlakhorn Jakkree , Manyam Jedsada , Srepusharawoot Pornjuk , Krongsuk Sriprajak , Thongbai Prasit
Published: May 2021

The effects of charge compensation on dielectric and electrical properties of CaCu3Ti4-x(Al1/2Ta1/4Nb1/4)xO12 ceramics (x = 0−0.05) prepared by a solid-state reaction method were studied based on the configuration of defect dipoles. A single phase of CaCu3Ti4O12 was observed in all ceramics with a slight change in lattice parameters. The mean grain size of CaCu3Ti4-x(Al1/2Ta1/4Nb1/4)xO12 ceramics was slightly smaller than that of the undoped ceramic. The dielectric loss tangent can be reduced by a factor of 13 (tanδ ~0.017), while the dielectric permittivity was higher than 104 over a wide frequency range. Impedance spectroscopy showed that the significant decrease in tanδ was attributed to the highly increased resistance of the grain boundary by two orders of magnitude. The DFT calculation showed that the preferential sites of Al and Nb/Ta were closed together in the Ti sites, forming self-charge compensation, and resulting in the enhanced potential barrier height at the grain boundary. Therefore, the improved dielectric properties of CaCu3Ti4-x(Al1/2Ta1/4Nb1/4)xO12 ceramics associated with the enhanced electrical properties of grain boundaries. In addition, the non-Ohmic properties were also improved. Characterization of the grain boundaries under a DC bias showed the reduction of potential barrier height at the grain boundary. The overall results indicated that the origin of the colossal dielectric properties was caused by the internal barrier layer capacitor structure, in which the Schottky barriers at the grain boundaries were formed.
Antioxidant and Anticholinesterase Activities of Extracts and Phytochemicals of Syzygium antisepticum Leaves
Authors: Mangmool Supachoke , Kunpukpong Issaree , Kitphati Worawan , Anantachoke Natthinee
Published: May 2021

Bioassay-guided separation of young leaves extracts of Syzygium antisepticum (Blume) Merr. & L.M. Perry led to the isolation of four triterpenoids (betulinic acid, ursolic acid, jacoumaric acid, corosolic acid) and one sterol glucoside (daucosterol) from the ethyl acetate extract, and three polyphenols (gallic acid, myricitrin, and quercitrin) from the methanol (MeOH) extract. The MeOH extract of S. antisepticum and some isolated compounds, ursolic acid and gallic acid potentially exhibited acetylcholinesterase activity evaluated by Ellman’s method. The MeOH extract and its isolated compounds, gallic acid, myricitrin, and quercitrin, also strongly elicited DPPH radical scavenging activity. In HEK-293 cells, the MeOH extract possessed cellular antioxidant effects by attenuating hydrogen peroxide (H2O2)-induced ROS production and increasing catalase, glutathione peroxidase-1 (GPx-1), and glutathione reductase (GRe). Furthermore, myricitrin and quercitrin also suppressed ROS production induced by H2O2 and induced GPx-1 and catalase production in HEK-293 cells. These results indicated that the young leaves of S. antisepticum are the potential sources of antioxidant and anticholinesterase agents. Consequently, S. antisepticum leaves are one of indigenous vegetables which advantage to promote the health and prevent diseases related to oxidative stress.
New Disulfiram Derivatives as MAGL-Selective Inhibitors
Authors: Omran Ziad
Published: May 2021

Monoacylglycerol lipase (MAGL) is a key enzyme in the human endocannabinoid system. It is also the main enzyme responsible for the conversion of 2-arachidonoyl glycerol (2-AG) to arachidonic acid (AA), a precursor of prostaglandin synthesis. The inhibition of MAGL activity would be beneficial for the treatment of a wide range of diseases, such as inflammation, neurodegeneration, metabolic disorders and cancer. Here, the author reports the pharmacological evaluation of new disulfiram derivatives as potent inhibitors of MAGL. These analogues displayed high inhibition selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. In particular, compound 2i inhibited MAGL in the low micromolar range. However, it did not show any inhibitory activity against FAAH.
Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells
Authors: Oh Jin Su , Seong Geum Su , Kim Yong Deok , Choung Se Young
Published: May 2021

The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.
The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery—The GL–Lect Hypothesis
Authors: Johannes Ludger
Published: May 2021

Lipid membranes are common to all forms of life. While being stable barriers that delimitate the cell as the fundamental organismal unit, biological membranes are highly dynamic by allowing for lateral diffusion, transbilayer passage via selective channels, and in eukaryotic cells for endocytic uptake through the formation of membrane bound vesicular or tubular carriers. Two of the most abundant fundamental fabrics of membranes—lipids and complex sugars—are produced through elaborate chains of biosynthetic enzymes, which makes it difficult to study them by conventional reverse genetics. This review illustrates how organic synthesis provides access to uncharted areas of membrane glycobiology research and its application to biomedicine. For this Special Issue on Chemical Biology Research in France, focus will be placed on synthetic approaches (i) to study endocytic functions of glycosylated proteins and lipids according to the GlycoLipid–Lectin (GL–Lect) hypothesis, notably that of Shiga toxin; (ii) to mechanistically dissect its endocytosis and intracellular trafficking with small molecule; and (iii) to devise intracellular delivery strategies for immunotherapy and tumor targeting. It will be pointed out how the chemical biologist’s view on lipids, sugars, and proteins synergizes with biophysics and modeling to “look” into the membrane for atomistic scale insights on molecular rearrangements that drive the biogenesis of endocytic carriers in processes of clathrin-independent endocytosis.
Machine Learning Approaches to Predict Hepatotoxicity Risk in Patients Receiving Nilotinib
Authors: Kim Jung-Sun , Han Ji-Min , Cho Yoon-Sook , Choi Kyung-Hee , Gwak Hye-Sun
Published: May 2021

Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61–0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.
Advances in Nanodelivery of Green Tea Catechins to Enhance the Anticancer Activity
Authors: Jiang Yike , Jiang Ziyi , Ma Lan , Huang Qingrong
Published: May 2021

Cancer is one of the leading causes of death globally. A variety of phenolic compounds display preventative and therapeutic effects against cancers. Green teas are rich in phenolics. Catechins are the most dominant phenolic component in green teas. Studies have shown that catechins have anticancer activity in various cancer models. The anticancer activity of catechins, however, may be compromised due to their low oral bioavailability. Nanodelivery emerges as a promising way to improve the oral bioavailability and anticancer activity of catechins. Research in this area has been actively conducted in recent decades. This review provides the molecular mechanisms of the anticancer effects of catechins, the factors that limit the oral bioavailability of catechins, and the latest advances of delivering catechins using nanodelivery systems through different routes to enhance their anticancer activity.
Oriental Hornet (Vespa orientalis) Larval Extracts Induce Antiproliferative, Antioxidant, Anti-Inflammatory, and Anti-Migratory Effects on MCF7 Cells
Authors: Zedan Amina , Sakran Mohamed , Bahattab Omar , Hawsawi Yousef , Al-Amer Osama , Oyouni Atif , Nasr Eldeen Samah , El-Magd Mohammed
Published: May 2021

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.
Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases
Authors: Filipczak Nina , Yalamarty Satya Siva Kishan , Li Xiang , Parveen Farzana , Torchilin Vladimir
Published: May 2021

Dendrimers comprise a specific group of macromolecules, which combine structural properties of both single molecules and long expanded polymers. The three-dimensional form of dendrimers and the extensive possibilities for use of additional substrates for their construction creates a multivalent potential and a wide possibility for medical, diagnostic and environmental purposes. Depending on their composition and structure, dendrimers have been of interest in many fields of science, ranging from chemistry, biotechnology to biochemical applications. These compounds have found wide application from the production of catalysts for their use as antibacterial, antifungal and antiviral agents. Of particular interest are peptide dendrimers as a medium for transport of therapeutic substances: synthetic vaccines against parasites, bacteria and viruses, contrast agents used in MRI, antibodies and genetic material. This review focuses on the description of the current classes of dendrimers, the methodology for their synthesis and briefly drawbacks of their properties and their use as potential therapies against infectious diseases.
Strain Modulation of Selectively and/or Globally Grown Ge Layers
Authors: Du Yong , Wang Guilei , Miao Yuanhao , Xu Buqing , Li Ben , Kong Zhenzhen , Yu Jiahan , Zhao Xuewei , Lin Hongxiao , Su Jiale , Han Jianghao , Liu Jinbiao , Dong Yan , Wang Wenwu , Radamson Henry H.
Published: May 2021

This article presents a novel method to grow a high-quality compressive-strain Ge epilayer on Si using the selective epitaxial growth (SEG) applying the RPCVD technique. The procedures are composed of a global growth of Ge layer on Si followed by a planarization using CMP as initial process steps. The growth parameters of the Ge layer were carefully optimized and after cycle-annealing treatments, the threading dislocation density (TDD) was reduced to 3 × 107 cm−2. As a result of this process, a tensile strain of 0.25% was induced, whereas the RMS value was as low as 0.81 nm. Later, these substrates were covered by an oxide layer and patterned to create trenches for selective epitaxy growth (SEG) of the Ge layer. In these structures, a type of compressive strain was formed in the SEG Ge top layer. The strain amount was −0.34%; meanwhile, the TDD and RMS surface roughness were 2 × 106 cm−2 and 0.68 nm, respectively. HRXRD and TEM results also verified the existence of compressive strain in selectively grown Ge layer. In contrast to the tensile strained Ge layer (globally grown), enhanced PL intensity by a factor of more than 2 is partially due to the improved material quality. The significantly high PL intensity is attributed to the improved crystalline quality of the selectively grown Ge layer. The change in direct bandgap energy of PL was observed, owing to the compressive strain introduced. Hall measurement shows that a selectively grown Ge layer possesses room temperature hole mobility up to 375 cm2/Vs, which is approximately 3 times larger than that of the Ge (132 cm2/Vs). Our work offers fundamental guidance for the growth of high-quality and compressive strain Ge epilayer on Si for future Ge-based optoelectronics integration applications.
Microstructural Evolution and Mechanical Properties of Graphene Oxide-Reinforced Ti6Al4V Matrix Composite Fabricated Using Spark Plasma Sintering
Authors: Song Ying , Liu Weiwei , Sun Yufeng , Guan Shaokang , Chen Yao
Published: May 2021

To achieve a further reduction in weight of titanium alloys and to satisfy the increasing demand of energy-saving for aerospace and automotive applications, a graphene oxide nanosheet-reinforced Ti6Al4V (GO/TC4) composite was successfully fabricated using spark plasma sintering (SPS). Contrary to the Widmanstätten microstructure of a monolithic TC4 sample, the microstructure of the composites displayed a typical basket-weave structure in virtue of the introduced residual tensile stress generated from the mismatch of coefficients of thermal expansion (CTE) between GO and TC4 during the phase transformation. Meanwhile, the in situ-formed TiC nanolayer and diffusion layer were identified at the GO–TC4 interface, which is expected to endow a stronger interfacial bonding. As compared with the TC4 sample, the TC4 composite with the addition of 0.27 wt.% GO exhibited a 0.2% yield strength of 921.8 MPa, an ultimate tensile strength of 1040.1 MPa, and an elongation of 5.3%, displaying a better balance of strength and ductility than that of the composite with a higher GO addition (0.54 wt.%). The synergetic strengthening mechanisms such as Orowan strengthening, enhanced dislocation density strengthening, and load transfer were confirmed. Among them, load transfer contributed greatly to the strength of the composites due to improved interfacial bonding between the GO fillers and TC4 matrix.
Actively Tunable Fano Resonance Based on a Bowtie-Shaped Black Phosphorus Terahertz Sensor
Authors: Huang Yan , Liu Yan , Shao Yao , Han Genquan , Zhang Jincheng , Hao Yue
Published: May 2021

An ultrasensitive Terahertz (THz) sensor consisting of the sub-wavelength bowtie black phosphorus (BP) and an annular gold (Au) ring is proposed. The interference between the resonance generated by the bowtie BP and the Au ring creates a Fano-type resonance and makes ultrasensitive sensing realizable. Firstly, we demonstrate the Fano resonance of the coupled nanostructures by adjusting the geometry dimensions of the Au ring and the Fermi level of BP. Moreover, the Poynting vector distributions of the THz sensor are simulated to analyze the properties of Fano resonance. Importantly, a figure of merit (FOM) value as high as 69.3 is achieved and the proposed Fano resonance sensor shows a maximum sensitivity of 9.3 μm/RIU. Our structure can function as a facile and efficient building block of biochemical nano-sensing application based on Fano resonance at THz frequency.
Thermal and Quasi-Static Mechanical Characterization of Polyamide 6-Graphene Nanoplatelets Composites
Authors: Russo Pietro , Cimino Francesca , Tufano Antonio , Fabbrocino Francesco
Published: May 2021

The growing demand for lightweight and multifunctional products in numerous industrial fields has recently fuelled a growing interest in the development of materials based on polymer matrices including graphene-like particles, intrinsically characterized by outstanding mechanical, thermal, and electrical properties. Specifically, with regard to one of the main mass sectors, which is the automotive, there has been a significant increase in the use of reinforced polyamides for underhood applications and fuel systems thanks to their thermal and chemical resistance. In this frame, polyamide 6 (PA6) composites filled with graphene nanoplatelets (GNPs) were obtained by melt-compounding and compared in terms of thermal and mechanical properties with the neat matrix processed under the same condition. The results of the experimental tests have shown that the formulations studied so far offer slight improvements in terms of thermal stability but much more appreciable benefits regarding both tensile and flexural parameters with respect to the reference material. Among these effects, the influence of the filler content on the strength parameter is noteworthy. However, the predictable worsening of the graphene sheet dispersion for GNPs contents greater than 3%, as witnessed by scanning electron images of the tensile fractured sections of specimens, affected the ultimate performance of the more concentrated formulation.
Serological Evidence of Multiple Zoonotic Viral Infections among Wild Rodents in Barbados
Authors: Douglas Kirk Osmond , Cayol Claire , Forbes Kristian Michael , Samuels Thelma Alafia , Vapalahti Olli , Sironen Tarja , Gittens-St. Hilaire Marquita
Published: May 2021

Background: Rodents are reservoirs for several zoonotic pathogens that can cause human infectious diseases, including orthohantaviruses, mammarenaviruses and orthopoxviruses. Evidence exists for these viruses circulating among rodents and causing human infections in the Americas, but much less evidence exists for their presence in wild rodents in the Caribbean. Methods: Here, we conducted serological and molecular investigations of wild rodents in Barbados to determine the prevalence of orthohantavirus, mammarenavirus and orthopoxvirus infections, and the possible role of these rodent species as reservoirs of zoonotic pathogens. Using immunofluorescent assays (IFA), rodent sera were screened for the presence of antibodies to orthohantavirus, mammarenavirus (Lymphocytic choriomeningitis virus—LCMV) and orthopoxvirus (Cowpox virus—CPXV) infections. RT-PCR was then conducted on orthohantavirus and mammarenavirus-seropositive rodent sera and tissues, to detect the presence of viral RNA. Results: We identified antibodies against orthohantavirus, mammarenavirus, and orthopoxvirus among wild mice and rats (3.8%, 2.5% and 7.5% seropositivity rates respectively) in Barbados. No orthohantavirus or mammarenavirus viral RNA was detected from seropositive rodent sera or tissues using RT–PCR. Conclusions: Key findings of this study are the first serological evidence of orthohantavirus infections in Mus musculus and the first serological evidence of mammarenavirus and orthopoxvirus infections in Rattus norvegicus and M. musculus in the English-speaking Caribbean. Rodents may present a potential zoonotic and biosecurity risk for transmission of three human pathogens, namely orthohantaviruses, mammarenaviruses and orthopoxviruses in Barbados.
Serum Samples from Co-Infected and Domestic Cat Field Isolates Nonspecifically Bind FIV and Other Antigens in Enzyme-Linked Immunosorbent Assays
Authors: Moskaluk Alex , Nehring Mary , VandeWoude Sue
Published: May 2021

We evaluated enzyme-linked immunosorbent assay (ELISA) specificity for measuring seroantibody responses to two types of retroviral infections in domestic cats: feline immunodeficiency virus (FIV) and feline foamy virus (FFV). We compared the seroreactivity of specific pathogen-free (SPF) cat sera, sera from SPF cats inoculated with either FIV or FFV, and field isolates (e.g., shelter or privately owned cats). Sera from SPF cats experimentally infected with the cognate virus had significantly lower background in both FIV and FFV ELISAs compared to sera from negative field isolates. ELISA values for SPF cats exposed to either FIV or FFV tended to have higher OD values on the opposite ELISA antigen plate. FIV nonspecific background absorbance was greater than that of FFV, and 10 of 15 sera samples from FIV seronegative field samples were measured in the indeterminant range. These findings highlight that exposure to off-target pathogens elicit antibodies that may nonspecifically bind to antigens used in binding assays; therefore, validation using sera from SPF animals exposed during controlled infection results in the setting of a cutoff value that may be inappropriately low when applied to field samples. Our work also suggests that infection of domestic cats with pathogens other than FIV results in antibodies that cross-react with the FIV Gag antigen.
Survey of Viral Reactivations in Elite Athletes: A Case-Control Study
Authors: Pyöriä Lari , Valtonen Maarit , Luoto Raakel , Grönroos Wilma , Waris Matti , Heinonen Olli , Ruuskanen Olli , Perdomo Maria
Published: May 2021

Exercise-induced immune perturbations have been proposed to increase susceptibility to viral infections. We investigated the replication of persisting viruses as indicators of immune function in elite cross-country skiers after ten months of sustained high-performance exercise. The viruses evaluated, nine human herpesviruses (HHVs) and torque teno virus (TTV), are typically restrained in health but replicate actively in immunosuppressed individuals. We collected sera from 27 Finnish elite cross-country skiers at the end of the competition’s season and 27 matched controls who perform moderate exercise. We quantified all the HHVs and—TTV via highly sensitive qPCRs. To verify equal past exposures between the groups, we assessed the IgG antibody prevalences toward HHV-4 (Epstein–Barr virus, EBV) and HHV-5 (human cytomegalovirus, HCMV). We found equal TTV DNA prevalences in athletes (63%) and controls (63%) and loads with respective geometric means of 1.7 × 103 and 1.2 × 103 copies/mL of serum. Overall, the copy numbers were low and consistent with those of healthy individuals. Neither of the groups presented with herpesvirus viremia despite similar past exposures to HHVs (seroprevalences of EBV 70% vs. 78% and HCMV 52% vs. 44% in athletes and controls, respectively). We found no evidence of increased replication of persistent viruses in elite athletes, arguing against impaired viral immunity due to high-performance exercise.
Search for Promising Strains of Probiotic Microbiota Isolated from Different Biotopes of Healthy Cats for Use in the Control of Surgical Infections
Authors: Rudenko Pavel , Vatnikov Yuriy , Sachivkina Nadezhda , Rudenko Andrei , Kulikov Evgeny , Lutsay Vladimir , Notina Elena , Bykova Irina , Petrov Aleksander , Drukovskiy Stanislav , Olabode Ifarajimi Rapheal
Published: May 2021

Despite the introduction of modern methods of treatment, the creation of new generations of antibacterial agents, and the constant improvement of aseptic and antiseptic methods, the treatment of purulent–inflammatory processes remains one of the most complex and urgent problems in veterinary practice. The article presents the results of the isolation of indigenous microbiota from various biotopes of healthy cats, as well as the study of their biological marker properties for the selection of the most optimal strains in probiotic medicines for the control of surgical infections. It was demonstrated that isolated cultures of bifidobacteria and lactobacilli, which we isolated, revealed high sensitivity to antibiotics of the β-lactam group (excepting L. acidophilus No. 24, L. plantarum “Victoria” No. 22, L. rhamnosus No. 5, L. rhamnosus No. 20, and L. rhamnosus No. 26, which showed a significant variability in sensitivity to antibacterial drugs of this group, indicating the great potential of these microorganisms) and resistance to aminoglycosides, lincosamides, and fluoroquinolones (with the exception of gatifloxacin, which showed high efficiency in relation to all lactic acid microorganisms). The adhesive properties of the isolated lactobacteria and bifidobacteria were variable, even within the same species. It was found that the B. adolescentis No. 23 strain of the Bifidobacterium genus, as well as the L. plantarum No. 8, L. plantarum “Victoria” No. 22, L. rhamnosus No. 6, L. rhamnosus No. 26, L. acidophilus No. 12, and L. acidophilus No. 24 strains of the Lactobacillus genus had the highest adhesive activity. Thus, when conducting a detailed analysis of the biological marker properties of candidate cultures (determining their sensitivity to antimicrobial agents, studying the adhesive properties, and antagonistic activity in relation to causative agents of surgical infection in cats), it was found that the most promising are L. plantarum “Victoria” No. 22, L. rhamnosus No. 26, and L. acidophilus No. 24.
Progress towards Sustainable Control of Xylella fastidiosa subsp. pauca in Olive Groves of Salento (Apulia, Italy)
Authors: Scortichini Marco , Loreti Stefania , Pucci Nicoletta , Scala Valeria , Tatulli Giuseppe , Verweire Dimitri , Oehl Michael , Widmer Urs , Codina Josep Massana , Hertl Peter , Cesari Gianluigi , De Caroli Monica , Angilè Federica , Migoni Danilo , Del Coco Laura , Girelli Chiara Roberta , Dalessandro Giuseppe , Fanizzi Francesco Paolo
Published: May 2021

Xylella fastidiosa subsp. pauca is the causal agent of “olive quick decline syndrome” in Salento (Apulia, Italy). On April 2015, we started interdisciplinary studies to provide a sustainable control strategy for this pathogen that threatens the multi-millennial olive agroecosystem of Salento. Confocal laser scanning microscopy and fluorescence quantification showed that a zinc-copper-citric acid biocomplex—Dentamet®—reached the olive xylem tissue either after the spraying of the canopy or injection into the trunk, demonstrating its effective systemicity. The biocomplex showed in vitro bactericidal activity towards all X. fastidiosa subspecies. A mid-term evaluation of the control strategy performed in some olive groves of Salento indicated that this biocomplex significantly reduced both the symptoms and X. f. subsp. pauca cell concentration within the leaves of the local cultivars Ogliarola salentina and Cellina di Nardò. The treated trees started again to yield. A 1H-NMR metabolomic approach revealed, upon the treatments, a consistent increase in malic acid and γ-aminobutyrate for Ogliarola salentina and Cellina di Nardò trees, respectively. A novel endotherapy technique allowed injection of Dentamet® at low pressure directly into the vascular system of the tree and is currently under study for the promotion of resprouting in severely attacked trees. There are currently more than 700 ha of olive groves in Salento where this strategy is being applied to control X. f. subsp. pauca. These results collectively demonstrate an efficient, simple, low-cost, and environmentally sustainable strategy to control this pathogen in Salento.
The M35 Metalloprotease Effector FocM35_1 Is Required for Full Virulence of Fusarium oxysporum f. sp. cubense Tropical Race 4
Authors: Zhang Xiaoxia , Huang Huoqing , Wu Bangting , Xie Jianghui , Viljoen Altus , Wang Wei , Mostert Diane , Xie Yanling , Fu Gang , Xiang Dandan , Lyu Shuxia , Liu Siwen , Li Chunyu
Published: May 2021

Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes Fusarium wilt of banana, the most devastating disease on a banana plant. The genome of Foc TR4 encodes many candidate effector proteins. However, little is known about the functions of these effector proteins on their contributions to disease development and Foc TR4 virulence. Here, we discovered a secreted metalloprotease, FocM35_1, which is an essential virulence effector of Foc TR4. FocM35_1 was highly upregulated during the early stages of Foc TR4 infection progress in bananas. The FocM35_1 knockout mutant compromised the virulence of Foc TR4. FocM35_1 could interact with the banana chitinase MaChiA, and it decreased banana chitinase activity. FocM35_1 induced cell death in Nicotiana benthamiana while suppressing the INF1-induced hypersensitive response (HR), and its predicted enzymatic site was required for lesion formation and the suppression to INF1-induced HR on N. benthamiana leaves. Importantly, treatment of banana leaves with recombinant FocM35_1 accelerates Foc TR4 infection. Collectively, our study provides evidence that metalloprotease effector FocM35 seems to contribute to pathogen virulence by inhibiting the host immunity.
HEV-Associated Neuralgic Amyotrophy: A Multicentric Case Series
Authors: Bannasch Johannes H. , Berger Benjamin , Schwartkop Claus-Peter , Berning Marco , Goetze Oliver , Panning Marcus , Fritz-Weltin Miriam , Trendelenburg George , Gelderblom Mathias , Lütgehetmann Marc , Stute Fridrike , Horvatits Thomas , Dirks Meike , Antoni Christoph , Behrendt Patrick , Pischke Sven
Published: May 2021

Background: Neuralgic amyotrophy (NA) has been described as a possible extrahepatic manifestation of hepatitis E virus (HEV) infection. Usually, HEV-associated NA occurs bilaterally. The clinical characteristics determining the course of HEV-associated NA have still not been defined. Methods: In this retrospective multicentric case series, 16 patients with HEV-associated NA were studied and compared to 176 HEV patients without NA in terms of their age, sex, and ALT levels. Results: Neither gender distribution (75% vs. 67% male) nor age (47 vs. 48 years median) differed significantly between the NA patients and controls. Eight NA patients (50%) presented with bilateral involvement—seven of these had right-side dominance and one had left-side dominance. Thirteen cases (81%) were hospitalized. Eight of these patients stayed in hospital for five to seven days, and five patients stayed for up to two weeks. The time from the onset of NA to the HEV diagnosis, as well as the diagnostic and therapeutic proceedings, showed a large variability. In total, 13 (81%) patients received treatment: 1/13 (8%) received intravenous immunoglobulins, 8/13 (62%) received glucocorticoids, 3/13 (23%) received ribavirin, and 6/13 (46%) received pregabalin/gabapentin. Patients with ages above the median (47 years) were more likely to be treated (p = 0.001). Conclusion: HEV-associated NA causes a relevant morbidity. In our case series neither the type of treatment nor the time of initiation of therapy had a significant effect on the duration of hospitalization or the course of the disease. The clinical presentation, the common diagnostic and therapeutic procedures, and the patients’ characteristics showed large variability, demonstrating the necessity of standardized protocols for this rare but relevant disease.
Prevalence and Genetic Diversity of Group A Rotavirus Genotypes in Moscow (2019–2020)
Authors: Yuzhakov Anton , Yuzhakova Ksenia , Kulikova Nadezhda , Kisteneva Lidia , Cherepushkin Stanislav , Smetanina Svetlana , Bazarova Marina , Syroeshkin Anton , Grebennikova Tatiana
Published: May 2021

Group A rotavirus (RVA) infection is the leading cause of hospitalization of children under 5 years old, presenting with symptoms of acute gastroenteritis. The aim of our study was to explore the genetic diversity of RVA among patients admitted to Moscow Infectious Disease Clinical Hospital No. 1 with symptoms of acute gastroenteritis. A total of 653 samples were collected from May 2019 through March 2020. Out of them, 135 (20.67%) fecal samples were found to be positive for rotavirus antigen by ELISA. RT-PCR detected rotavirus RNA in 80 samples. Seven G-genotypes (G1, G2, G3, G4, G8, G9, and G12) and three P-genotypes (P[8], P[4], and P[6]) formed 9 different combinations. The most common combination was G9P[8]. However, for the first time in Moscow, the combination G3P[8] took second place. Moreover, all detected viruses of this combination belonged to Equine-like G3P[8] viruses that had never been detected in Russia before. The genotype G8P[8] and G9P[4] rotaviruses were also detected in Moscow for the first time. Among the studied rotaviruses, there were equal proportions of Wa and DS-1-like strains; previous studies showed that Wa-like strains accounted for the largest proportion of rotaviruses in Russia.
Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?
Authors: Elmanfi Samira , Yilmaz Mustafa , Ong Wilson W. S. , Yeboah Kofi S. , Sintim Herman O. , Gürsoy Mervi , Könönen Eija , Gürsoy Ulvi K.
Published: May 2021

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.
A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
Authors: Cimica Velasco , Saleem Sahar , Matuczinski Emily , Adams-Fish Debra , McMahon Conor , Rashid Sujatha , Stedman Timothy
Published: May 2021

Powassan virus (POWV) is a tick-borne flavivirus circulating in North America and the Russian Far East that can cause severe neuroinvasive diseases, including encephalitis, meningitis, and meningoencephalitis. The reported neuroinvasive case fatality is about 10%, and approximately 50% of the survivors from the neuroinfection exhibit long-lasting or permanent neurological sequelae. Currently, treatment of POWV infection is supportive, and no FDA-approved vaccines or specific therapeutics are available. A novel Powassan vaccine candidate was created using virus-like particle technology (POW-VLP) and assembled with the viral structural proteins pre-Membrane (prM) and Envelope (E). Western blot immunoassay demonstrated high antigenicity of POW-VLP structural proteins. Transmission electron microscopy indicated that the POW-VLP exhibited icosahedral morphology typical of flaviviruses. A dose-escalation study in a murine model was performed to test immunogenicity and safety. Serum antibody was tested by ELISA, demonstrating that POW-VLP afforded 100% seroconversion to the E protein. Reporter viral-particle neutralization assay demonstrated high levels of neutralizing antibodies in the serum of immunized mice. Hybridomas expressing monoclonal antibodies were produced following POW-VLP immunization. The POW-VLP vaccine candidate created in this study provides a strategy for inducing protective antibodies against Powassan neuroinvasive infection.
miR-34a-Mediated Survivin Inhibition Improves the Antitumor Activity of Selinexor in Triple-Negative Breast Cancer
Authors: Martini Silvia , Zuco Valentina , Tortoreto Monica , Percio Stefano , Campi Elisa , El Bezawy Rihan , Doldi Valentina , Landesman Yosef , Pennati Marzia , Zaffaroni Nadia
Published: May 2021

Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Here, we pursued a combinatorial therapeutic approach to enhance the activity of selinexor, the first-in-class XPO1 inhibitor, by miR-34a ectopic expression in human TNBC experimental models. Anti-proliferative activity induced by selinexor and miR-34a expression, singly and in combination, was evaluated by MTS assay and cell counting. The effect of treatments on survivin and apoptosis-related proteins was assessed by western blotting and ELISA. The antitumor and toxic effects of individual and combined treatments were evaluated on TNBC orthotopic xenografts in SCID mice. Selinexor consistently showed anti-proliferative activity, although to a variable extent, in the different TNBC cell lines and caused the impairment of survivin expression and intracellular distribution, accompanied by apoptosis induction. Consistent with in vitro data, the XPO1 inhibitor variably affected the growth of TNBC orthotopic xenografts. miR-34a cooperated with selinexor to reduce survivin expression and improved its anti-proliferative activity in TNBC cells. Most importantly, miR-34a expression markedly enhanced selinexor antitumor activity in the less sensitive TNBC xenograft model, in absence of toxicity. Our data form a solid foundation for promoting the use of a miR-34a-based approach to improve the therapeutic efficacy of selinexor in TNBC patients.
Review of Helical Long-Period Fiber Gratings
Authors: Ma Chao , Wang Jian , Yuan Libo
Published: May 2021

In this paper, comprehensive remarks are given that focus on the main fabrications and wide applications of helical long-period fiber gratings (HLPGs). Firstly, the techniques of fabricating HLPGs by CO2 laser, hydrogen–oxygen flame heating, and arc discharge are summarized. Furthermore, the applications of HLPGs are investigated, i.e., orbital angular momentum (OAM) mode converters, all-fiber band-rejection filters, and sensors for measuring physical perturbation of torsion, strain, temperature, curvature, and surrounding refractive index (SRI). Furthermore, several long-period fiber gratings (LPFGs) of near-HLPG structures with periodic refractive index change along the azimuthal direction are introduced. Lastly, the prospects and key challenges for HLPGs are discussed.