bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Silencing of HER2 Expression during Epithelial-Mesenchymal Transition Leads to Trastuzumab Resistance in Breast Cancer
Authors: Nami Babak , Ghanaeian Avrin , Black Corbin , Wang Zhixiang
Published: August 2021

HER2 receptor tyrosine kinase (encoded by the ERBB2 gene) is overexpressed in approximately 25% of all breast cancer tumors (HER2-positive breast cancers). Resistance to HER2-targeting therapies is partially due to the loss of HER2 expression in tumor cells during treatment. However, little is known about the exact mechanism of HER2 downregulation in HER2-positive tumor cells. Here, by analyzing publicly available genomic data we investigate the hypothesis that epithelial-mesenchymal transition (EMT) abrogates HER2 expression by epigenetic silencing of the ERBB2 gene as a mechanism of acquired resistance to HER2-targeted therapies. As result, HER2 expression was found to be positively and negatively correlated with the expression of epithelial and mesenchymal phenotype marker genes, respectively. The ERBB2 chromatin of HER2-high epithelial-like breast cancer cells and HER2-low mesenchymal-like cells were found to be open/active and closed/inactive, respectively. Decreased HER2 expression was correlated with increased EMT phenotype, inactivated chromatin and lower response to lapatinib. We also found that induction of EMT in the HER2-positive breast cancer cell line BT474 resulted in downregulated HER2 expression and reduced trastuzumab binding. Our results suggest that ERBB2 gene silencing by epigenetic regulation during EMT may be a mechanism of de novo resistance of HER2-positive breast cancer cells to trastuzumab and lapatinib.
State-of-the-Art on Biomarkers for Anaphylaxis in Obstetrics
Authors: Simionescu Anca Angela , Stanescu Ana Maria Alexandra , Popescu Florin-Dan
Published: August 2021

Anaphylaxis is an unpredictable systemic hypersensitivity reaction and constitutes a high risk of maternal and fetal morbidity and mortality when occurring during pregnancy. Currently, the acute management of anaphylaxis is based on clinical parameters. A total serum tryptase is only used to support an accurate diagnosis. There is a need to detect other biomarkers to further assess high-risk patients in obstetrics. Our objective is to present biomarkers in this complex interdisciplinary approach beyond obstetrician and anaesthetic management. Candidate biomarkers derive either from mediators involved in immunopathogenesis or upcoming molecules from systems biology and proteomics. Serum tryptase is determined by singleplex immunoassay method and is important in the evaluation of anaphylactic mast cell degranulation but also in the assessment of other risk factors for anaphylaxis such as systemic mastocytosis. Another category of biomarkers investigates the IgE-mediated sensitization to triggers potentially involved in the etiology of anaphylaxis in pregnant women, using singleplex or multiplex immunoassays. These in vitro tests with natural extracts from foods, venoms, latex or drugs, as well as with molecular allergen components, are useful because in vivo allergy tests cannot be performed on pregnant women in such a major medical emergency due to their additional potential risk of anaphylaxis.
Dung Beetle Assemblages Attracted to Cow and Horse Dung: The Importance of Mouthpart Traits, Body Size, and Nesting Behavior in the Community Assembly Process
Authors: Tonelli Mattia , Giménez Gómez Victoria C. , Verdú José R. , Casanoves Fernando , Zunino Mario
Published: August 2021

Dung beetles use excrement for feeding and reproductive purposes. Although they use a range of dung types, there have been several reports of dung beetles showing a preference for certain feces. However, exactly what determines dung preference in dung beetles remains controversial. In the present study, we investigated differences in dung beetle communities attracted to horse or cow dung from a functional diversity standpoint. Specifically, by examining 18 functional traits, we sought to understand if the dung beetle assembly process is mediated by particular traits in different dung types. Species specific dung preferences were recorded for eight species, two of which prefer horse dung and six of which prefer cow dung. Significant differences were found between the functional traits of the mouthparts of the dung beetles attracted to horse dung and those that were attracted to cow dung. Specifically, zygum development and the percentage of the molar area and the conjunctive area differed between horse and cow dung colonizing beetles. We propose that the quantitative differences in the mouthpart traits of the species attracted to horse and cow dung respectively could be related to the differential capacity of the beetles to filtrate and concentrate small particles from the dung. Hence, the dung preference of dung beetles could be related to their ability to exploit a specific dung type, which varies according to their mouthpart traits. Moreover, we found that larger and nester beetles preferred cow dung, whereas smaller and non-nester beetles preferred horse dung. This finding could be related to the tradeoff between fitness and parental investments, and to the suitability of the trophic resource according to the season and species phenology.
Microstructural Design of Necklace-Like Fe3O4/Multiwall Carbon Nanotube (MWCNT) Composites with Enhanced Microwave Absorption Performance
Authors: Zhang Mu , Song Sinan , Liu Yamin , Hou Zaoxia , Tang Wenyi , Li Shengnan
Published: August 2021

In order to manufacture microwave absorbers with strong attenuation abilities and that are light weight, in this paper, ferromagnetic carbon matrix composites were prepared by the composite of carbon nanotubes with adjustable dielectric constant and Fe3O4. Fe3O4/MWCNT composites with well-designed necklace-like structure and controllable size in the range of 100–400 nm have been successfully achieved by a simple solvent thermal method. A series of samples were prepared by changing experimental parameters. The microwave absorption characteristics of these samples were studied from the dielectric constant and magnetic permeability in two aspects. The electromagnetic absorption properties of the composites show obvious differences with different microsphere sizes, different microsphere density and different proportion of additives. When the solvothermal time is 15 h and the microsphere size is 400 nm, the reflection loss reaches −38 dB. The interfacial polarization caused by the unique structural design and good impedance matching produce composites that possess excellent electromagnetic loss ability.
Effect of Microstructure on the Dimensional Stability of Extruded Pure Aluminum
Authors: Fu Linlin , Wu Gaohui , Zhou Chang , Xiu Ziyang , Yang Wenshu , Qiao Jing
Published: August 2021

High-performance extruded aluminum alloys with complex textures suffer significant dimension variation under environmental temperature fluctuations, dramatically decreasing the precision of navigation systems. This research mainly focuses on the effect of the texture of extruded pure aluminum on its dimensional stability after various annealing processes. The result reveals that a significant increment in the area fraction of recrystallized grains with <100> orientation and a decrement in the area fraction of grains with <111> orientation were found with increasing annealing temperature. Moreover, with the annealing temperature increasing from 150 °C to 400 °C, the residual plastic strain after twelve thermal cycles with a temperature range of 120 °C was changed from −1.6 × 10−5 to −4.5 × 10−5. The large amount of equiaxed grains with <100> orientation was formed in the microstructure of the extruded pure aluminum and the average grain size was decreased during thermal cycling. The area fraction of grain with <100> crystallographic orientation of the sample annealed at 400 °C after thermal cycling was 30.9% higher than annealed at 350 °C (23.7%) or at 150 °C (18.7%). It is attributed to the increase in the proportion of recrystallization grains with <100> direction as the annealing temperature increases, provided more nucleation sites for the formation of fine equiaxed grains with <100> orientation. The main orientation of the texture was rotated from parallel to <111> to parallel to <100> after thermal cycling. The change in the orientation of grains contributed to a change in interplanar spacing, which explains the change in the dimension along the extrusion direction during thermal cycling.
Irradiance-Controlled Photoassisted Synthesis of Sub-Nanometre Sized Ruthenium Nanoparticles as Co-Catalyst for TiO2 in Photocatalytic Reactions
Authors: García-Muñoz Patricia , Fresno Fernando , Ivanez Javier , Keller Nicolas
Published: August 2021

Photoassisted synthesis is as a highly appealing green procedure for controlled decoration of semiconductor catalysts with co-catalyst nanoparticles, which can be carried out without the concourse of elevated temperatures, external chemical reducing agents or applied bias potential and in a simple slurry reactor. The aim of this study is to evaluate the control that such a photoassisted method can exert on the properties of ruthenium nanoparticles supported on TiO2 by means of the variation of the incident irradiance and hence of the photodeposition rate. For that purpose, different Ru/TiO2 systems with the same metal load have been prepared under varying irradiance and characterized by means of elemental analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The photocatalytic activity of the so-obtained materials has been evaluated by using the degradation of formic acid in water under UV-A light. Particles with size around or below one nanometer were obtained, depending on the irradiance employed in the synthesis, with narrow size distribution and homogeneous dispersion over the titania support. The relation between neutral and positive oxidation states of ruthenium could also be controlled by the variation of the irradiance. The obtained photocatalytic activities for formic acid oxidation were in all cases higher than that of undecorated titania, with the sample obtained with the lowest irradiation giving rise to the highest oxidation rate. According to the catalysts characterization, photocatalytic activity is influenced by both Ru size and Ru0/Ruδ+ ratio.
Determination of the Spatial Anisotropy of the Surface MicroStructures of Different Implant Materials: An Atomic Force Microscopy Study
Authors: Gambardella Alessandro , Marchiori Gregorio , Maglio Melania , Russo Alessandro , Rossi Chiara , Visani Andrea , Fini Milena
Published: August 2021

Many biomaterials’ surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio Str and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the “two parameters” approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications.
A Nonhomogeneous Boundary Value Problem for Steady State Navier-Stokes Equations in a Multiply-Connected Cusp Domain
Authors: Kaulakytė Kristina , Pileckas Konstantinas
Published: August 2021

The boundary value problem for the steady Navier–Stokes system is considered in a 2D multiply-connected bounded domain with the boundary having a power cusp singularity at the point O. The case of a boundary value with nonzero flow rates over connected components of the boundary is studied. It is also supposed that there is a source/sink in O. In this case the solution necessarily has an infinite Dirichlet integral. The existence of a solution to this problem is proved assuming that the flow rates are “sufficiently small”. This condition does not require the norm of the boundary data to be small. The solution is constructed as the sum of a function with the finite Dirichlet integral and a singular part coinciding with the asymptotic decomposition near the cusp point.
Thirtieth Anniversary of the Discovery of Laxaphycins. Intriguing Peptides Keeping a Part of Their Mystery
Authors: Darcel Laurine , Das Sanjit , Bonnard Isabelle , Banaigs Bernard , Inguimbert Nicolas
Published: August 2021

Lipopeptides are a class of compounds generally produced by microorganisms through hybrid biosynthetic pathways involving non-ribosomal peptide synthase and a polyketyl synthase. Cyanobacterial-produced laxaphycins are examples of this family of compounds that have expanded over the past three decades. These compounds benefit from technological advances helping in their synthesis and characterization, as well as in deciphering their biosynthesis. The present article attempts to summarize most of the articles that have been published on laxaphycins. The current knowledge on the ecological role of these complex sets of compounds will also be examined.
Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants
Authors: Durães Fernando , Szemerédi Nikoletta , Kumla Decha , Pinto Madalena , Kijjoa Anake , Spengler Gabriella , Sousa Emília
Published: August 2021

Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which can be used in combination with approved antimicrobial drugs. In this work, a library of nineteen marine natural products, isolated from marine-derived fungi of the genera Neosartorya and Aspergillus, was evaluated for their potential as bacterial efflux pump inhibitors as well as the antimicrobial-related mechanisms, such as inhibition of biofilm formation and quorum-sensing. Docking studies were performed to predict their efflux pump action. These compounds were also tested for their cytotoxicity in mouse fibroblast cell line NIH/3T3. The results obtained suggest that the marine-derived fungal metabolites are a promising source of compounds with potential to revert antimicrobial resistance and serve as an inspiration for the synthesis of new antimicrobial drugs.
Cell Models for Chromosome 20q11.21 Amplification and Drug Sensitivities in Colorectal Cancer
Authors: Voutsadakis Ioannis A.
Published: August 2021

Background and objectives: The chromosome locus 20q11.21 is a commonly amplified locus in colorectal cancer, with a prevalence of 8% to 9%. Several candidate cancer-associated genes are transcribed from the locus. The therapeutic implications of the amplification in colorectal cancer remain unclear. Materials and Methods: Preclinical cell line models of colorectal cancer included in the Cancer Cell Line Encyclopedia (CCLE) collection were examined for the presence of amplifications in 20q11.21 genes. Correlations of the presence of 20q11.21 amplifications with gene essentialities and drug sensitivities were surveyed on salient databases for determination of therapeutic leads. Results: A significant subset of colorectal cancer cell lines in the CCLE (12 of 63 cell lines, 19%) bear amplifications of genes located at 20q11.21. Cancer-associated genes of the locus include ASXL1, DNMT3B, BCL2L1, TPX2, KIF3B and POFUT1. These genes are all amplified in the 12 cell lines, but they are variably over-expressed at the mRNA level, compared to non-amplified lines. 20q11.21 amplified cell lines are sensitive to various tyrosine kinase inhibitors and are resistant to chemotherapy drugs targeting the mitotic apparatus and microtubules. CRISPR and RNAi dependencies screening revealed, besides the β-catenin and KRAS genes, a few recurrent gene dependencies in more than one cell line, including YAP1 and JUP. Conclusions: Cell line models of colorectal cancer with 20q11.21 gene amplifications display dependencies on the presence of specific genes and resistance or sensitivity to specific drugs and drug categories. Observations from in vitro models may form the basis for clinical drug development in this subtype of colorectal cancer. Genetic lesions conferring synthetic lethality to certain drugs or categories of drugs could be discovered with this approach.
Effect of Cooling Rate and Modification by Strontium on the Thermal Conductivity of Al-8Si Alloy
Authors: Wang Guanyi , Guan Zhiping , Wang Jinguo , Ren Mingwen , Yan Ruifang , Song Jiawang
Published: August 2021

Cooling rate plays a critical role in determining the thermal conductivity of Al-Si alloys. Although the effect of morphology and size of Si (changed by heat treatment) on its thermal conductivity has been investigated, the effect of cooling rates on thermal conductivity has not been well studied. In this study, we investigated the microstructure of an Al-8Si (with and without modification by Strontium (Sr)) alloy with cooling rates from 46.2 °C/s to 234 °C/s. It was found that the effect of cooling rate on thermal conductivity of Sr modification and Sr-free samples are opposite from each other. As a result, while the cooling rate increased from 46.2 °C/s to 234 °C/s, the calculated thermal conductivity increased from 145.3 MS/m to 151.5 MS/m for Sr-free Al-8Si alloy, and the calculated thermal conductivity was reduced from 187.5 MS/m to 176.7 MS/m for the Sr-modified Al-8Si alloy. By discussing how thermal conductivity correlates with eutectic silicon morphology and secondary dendrite arm spacing, the relationship between cooling rate and thermal conductivity were explained. This work suggests a new design strategy for improving the thermal conductivity of Al-Si hypoeutectic alloys.
Compressive Properties and Failure Mechanisms of Gradient Aluminum Foams Prepared by a Powder Metallurgy Method
Authors: Huang Wenzhan , Liu Guangming , Li Huaying , Wang Fang , Wang Yanli
Published: August 2021

A layered gradient aluminum foam was prepared by powder sintering with sodium thiosulfate (Na2S2O3) particles as the cell-forming agent. By cutting, polishing and observing under a microscope, it was found that the aluminum powder particles were not completely melted after sintering but were only combined by surface melting. Based on the quasi-static compression test and the macroscopic diagram of the sample during deformation, the mechanical properties of gradient aluminum foam were studied, and their deformation characteristics and mechanism were analyzed and discussed.
Melatonin Ameliorates Thermotolerance in Soybean Seedling through Balancing Redox Homeostasis and Modulating Antioxidant Defense, Phytohormones and Polyamines Biosynthesis
Authors: Imran Muhammad , Aaqil Khan Muhammad , Shahzad Raheem , Bilal Saqib , Khan Murtaza , Yun Byung-Wook , Khan Abdul Latif , Lee In-Jung
Published: August 2021

Global warming is impacting the growth and development of economically important but sensitive crops, such as soybean (Glycine max L.). Using pleiotropic signaling molecules, melatonin can relieve the negative effects of high temperature by enhancing plant growth and development as well as modulating the defense system against abiotic stresses. However, less is known about how melatonin regulates the phytohormones and polyamines during heat stress. Our results showed that high temperature significantly increased ROS and decreased photosynthesis efficiency in soybean plants. Conversely, pretreatment with melatonin increased plant growth and photosynthetic pigments (chl a and chl b) and reduced oxidative stress via scavenging hydrogen peroxide and superoxide and reducing the MDA and electrolyte leakage contents. The inherent stress defense responses were further strengthened by the enhanced activities of antioxidants and upregulation of the expression of ascorbate–glutathione cycle genes. Melatonin mitigates heat stress by increasing several biochemicals (phenolics, flavonoids, and proline), as well as the endogenous melatonin and polyamines (spermine, spermidine, and putrescine). Furthermore, the positive effects of melatonin treatment also correlated with a reduced abscisic acid content, down-regulation of the gmNCED3, and up-regulation of catabolic genes (CYP707A1 and CYP707A2) during heat stress. Contrarily, an increase in salicylic acid and up-regulated expression of the defense-related gene PAL2 were revealed. In addition, melatonin induced the expression of heat shock protein 90 (gmHsp90) and heat shock transcription factor (gmHsfA2), suggesting promotion of ROS detoxification via the hydrogen peroxide-mediated signaling pathway. In conclusion, exogenous melatonin improves the thermotolerance of soybean plants and enhances plant growth and development by activating antioxidant defense mechanisms, interacting with plant hormones, and reprogramming the biochemical metabolism.
Low-Frequency Ultrasound Coupled with High-Pressure Technologies: Impact of Hybridized Techniques on the Recovery of Phytochemical Compounds
Authors: Zabot Giovani Leone , Viganó Juliane , Silva Eric Keven
Published: August 2021

The coupling of innovative technologies has emerged as a smart alternative for the process intensification of bioactive compound extraction from plant matrices. In this regard, the development of hybridized techniques based on the low-frequency and high-power ultrasound and high-pressure technologies, such as supercritical fluid extraction, pressurized liquids extraction, and gas-expanded liquids extraction, can enhance the recovery yields of phytochemicals due to their different action mechanisms. Therefore, this paper reviewed and discussed the current scenario in this field where ultrasound-related technologies are coupled with high-pressure techniques. The main findings, gaps, challenges, advances in knowledge, innovations, and future perspectives were highlighted.
α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines
Authors: Herdiana Yedi , Wathoni Nasrul , Shamsuddin Shaharum , Muchtaridi Muchtaridi
Published: August 2021

α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment. This review summarizes the progress and development of AMG’s cytotoxicity and the mechanism of death BC cells. The combination of natural medicine and nanotechnology into a synergistic capital will provide various benefits. This information will aid in the development of AMG nanoparticle preparations and may open up new avenues for discovering an effective BC treatment.
Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil
Authors: Kitajima Maiko , Miura Marika , Nanashima Naoki , Tomisawa Toshiko , Takamagi Shizuka , Fujioka Miyuki , In Naoya , Osanai Tomohiro
Published: August 2021

Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension–anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger–hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.
Computational Prediction of Compound–Protein Interactions for Orphan Targets Using CGBVS
Authors: Kanai Chisato , Kawasaki Enzo , Murakami Ryuta , Morita Yusuke , Yoshimori Atsushi
Published: August 2021

A variety of Artificial Intelligence (AI)-based (Machine Learning) techniques have been developed with regard to in silico prediction of Compound–Protein interactions (CPI)—one of which is a technique we refer to as chemical genomics-based virtual screening (CGBVS). Prediction calculations done via pairwise kernel-based support vector machine (SVM) is the main feature of CGBVS which gives high prediction accuracy, with simple implementation and easy handling. We studied whether the CGBVS technique can identify ligands for targets without ligand information (orphan targets) using data from G protein-coupled receptor (GPCR) families. As the validation method, we tested whether the ligand prediction was correct for a virtual orphan GPCR in which all ligand information for one selected target was omitted from the training data. We have specifically expressed the results of this study as applicability index and developed a method to determine whether CGBVS can be used to predict GPCR ligands. Validation results showed that the prediction accuracy of each GPCR differed greatly, but models using Multiple Sequence Alignment (MSA) as the protein descriptor performed well in terms of overall prediction accuracy. We also discovered that the effect of the type compound descriptors on the prediction accuracy was less significant than that of the type of protein descriptors used. Furthermore, we found that the accuracy of the ligand prediction depends on the amount of ligand information with regard to GPCRs related to the target. Additionally, the prediction accuracy tends to be high if a large amount of ligand information for related proteins is used in the training.
ST-2191, an Anellated Bismorpholino Derivative of Oxy-Fingolimod, Shows Selective S1P1 Agonist and Functional Antagonist Potency In Vitro and In Vivo
Authors: Stepanovska Tanturovska Bisera , Zivkovic Aleksandra , Imeri Faik , Homann Thomas , Kleuser Burkhard , Stark Holger , Huwiler Andrea
Published: August 2021

Sphingosine 1-phosphate (S1P) is an extensively studied signaling molecule that contributes to cell proliferation, survival, migration and other functions through binding to specific S1P receptors. The cycle of S1P1 internalization upon S1P binding and recycling to the cell surface when local S1P concentrations are low drives T cell trafficking. S1P1 modulators, such as fingolimod, disrupt this recycling by inducing persistent S1P1 internalization and receptor degradation, which results in blocked egress of T cells from the secondary lymphoid tissues. The approval of these compounds for the treatment of multiple sclerosis has placed the development of S1PR modulators in the focus of pharmacological research, mostly for autoimmune indications. Here, we report on a novel anellated bismorpholino derivative of oxy-fingolimod, named ST-2191, which exerts selective S1P1 agonist and functional antagonist potency. ST-2191 is also effective in reducing the lymphocyte number in mice, and this effect is not dependent on phosphorylation by sphingosine kinase 2 for activity. These data show that ST-2191 is a novel S1P1 modulator, but further experiments are needed to analyze the therapeutic impact of ST-2191 in animal models of autoimmune diseases.
Modern Theoretical Approaches to Modeling the Excited-State Intramolecular Proton Transfer: An Overview
Authors: Jankowska Joanna , Sobolewski Andrzej L.
Published: August 2021

The excited-state intramolecular proton transfer (ESIPT) phenomenon is nowadays widely acknowledged to play a crucial role in many photobiological and photochemical processes. It is an extremely fast transformation, often taking place at sub-100 fs timescales. While its experimental characterization can be highly challenging, a rich manifold of theoretical approaches at different levels is nowadays available to support and guide experimental investigations. In this perspective, we summarize the state-of-the-art quantum-chemical methods, as well as molecular- and quantum-dynamics tools successfully applied in ESIPT process studies, focusing on a critical comparison of their specific properties.
ZIC-cHILIC Functionalized Magnetic Nanoparticle for Rapid and Sensitive Glycopeptide Enrichment from <1 µL Serum
Authors: Pradita Tiara , Chen Yi-Ju , Mernie Elias , Bendulo Sharine , Chen Yu-Ju
Published: August 2021

Due to their unique glycan composition and linkage, protein glycosylation plays significant roles in cellular function and is associated with various diseases. For comprehensive characterization of their extreme structural complexity occurring in >50% of human proteins, time-consuming multi-step enrichment of glycopeptides is required. Here we report zwitterionic n-dodecylphosphocholine-functionalized magnetic nanoparticles (ZIC-cHILIC@MNPs) as a highly efficient affinity nanoprobe for large-scale enrichment of glycopeptides. We demonstrate that ZIC-cHILIC@MNPs possess excellent affinity, with 80–91% specificity for glycopeptide enrichment, especially for sialylated glycopeptide (90%) from biofluid specimens. This strategy provides rapidity (~10 min) and high sensitivity (<1 μL serum) for the whole enrichment process in patient serum, likely due to the rapid separation using magnetic nanoparticles, fast reaction, and high performance of the affinity nanoprobe at nanoscale. Using this strategy, we achieved personalized profiles of patients with hepatitis B virus (HBV, n = 3) and hepatocellular carcinoma (HCC, n = 3) at the depth of >3000 glycopeptides, especially for the large-scale identification of under-explored sialylated glycopeptides. The glycoproteomics atlas also revealed the differential pattern of sialylated glycopeptides between HBV and HCC groups. The ZIC-cHILIC@MNPs could be a generic tool for advancing the glycoproteome analysis, and contribute to the screening of glycoprotein biomarkers.
Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis
Authors: Li Wusun , Lin Yingying , Luo Yujia , Wang Yuqi , Lu Yao , Li Yixuan , Guo Huiyuan
Published: August 2021

It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.
Reappraisal of PRRS Immune Control Strategies: The Way Forward
Authors: Amadori Massimo , Listorti Valeria , Razzuoli Elisabetta
Published: August 2021

The control of porcine reproductive and respiratory syndrome (PRRS) is still a major issue worldwide in the pig farming sector. Despite extensive research efforts and the practical experience gained so far, the syndrome still severely affects farmed pigs worldwide and challenges established beliefs in veterinary virology and immunology. The clinical and economic repercussions of PRRS are based on concomitant, additive features of the virus pathogenicity, host susceptibility, and the influence of environmental, microbial, and non-microbial stressors. This makes a case for integrated, multi-disciplinary research efforts, in which the three types of contributing factors are critically evaluated toward the development of successful disease control strategies. These efforts could be significantly eased by the definition of reliable markers of disease risk and virus pathogenicity. As for the host’s susceptibility to PRRSV infection and disease onset, the roles of both the innate and adaptive immune responses are still ill-defined. In particular, the overt discrepancy between passive and active immunity and the uncertain role of adaptive immunity vis-à-vis established PRRSV infection should prompt the scientific community to develop novel research schemes, in which apparently divergent and contradictory findings could be reconciled and eventually brought into a satisfactory conceptual framework.
The Liver and the Hepatic Immune Response in Trypanosoma cruzi Infection, a Historical and Updated View
Authors: Vacani-Martins Natalia , Meuser-Batista Marcelo , dos Santos Carina de Lima Pereira , Hasslocher-Moreno Alejandro Marcel , Henriques-Pons Andrea
Published: August 2021

Chagas disease was described more than a century ago and, despite great efforts to understand the underlying mechanisms that lead to cardiac and digestive manifestations in chronic patients, much remains to be clarified. The disease is found beyond Latin America, including Japan, the USA, France, Spain, and Australia, and is caused by the protozoan Trypanosoma cruzi. Dr. Carlos Chagas described Chagas disease in 1909 in Brazil, and hepatomegaly was among the clinical signs observed. Currently, hepatomegaly is cited in most papers published which either study acutely infected patients or experimental models, and we know that the parasite can infect multiple cell types in the liver, especially Kupffer cells and dendritic cells. Moreover, liver damage is more pronounced in cases of oral infection, which is mainly found in the Amazon region. However, the importance of liver involvement, including the hepatic immune response, in disease progression does not receive much attention. In this review, we present the very first paper published approaching the liver’s participation in the infection, as well as subsequent papers published in the last century, up to and including our recently published results. We propose that, after infection, activated peripheral T lymphocytes reach the liver and induce a shift to a pro-inflammatory ambient environment. Thus, there is an immunological integration and cooperation between peripheral and hepatic immunity, contributing to disease control.
Clinical Significance of Pleural Effusion in Mycoplasma pneumoniae Pneumonia in Children
Authors: Kim Seo-Hee , Lee Eun , Song Eun-Song , Lee Yun-Young
Published: August 2021

The clinical significance of pleural effusion in Mycoplasma pneumoniae (MP) pneumonia in children has not yet been elucidated. Herein, we investigated the clinical implications of pleural effusion in children with MP pneumonia. Overall, 150 children with MP pneumonia transferred to a tertiary hospital were enrolled in this study. Information on their clinical, laboratory, and radiological features was retrospectively obtained from medical chart reviews. In total, 24 (16.0%) children had pleural effusion at the time of admission. The duration of fever and length of hospitalization were significantly longer in the pleural effusion group than in the non-pleural effusion group. A significantly higher proportion of individuals in the pleural effusion group had a poor response to stepwise treatment for MP pneumonia. The mean C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase levels were significantly higher in the pleural effusion group than in the non-pleural effusion group at admission. The prevalence of severe pneumonia, defined on the basis of the extent of pneumonic lesions on chest radiography, was higher in the pleural effusion group than in the non-pleural effusion group. However, there was no significant intergroup difference in the proportion of macrolide-resistant MP cases or respiratory viral coinfections. The presence of pleural effusion in children with MP pneumonia indicated a more severe clinical course and poor treatment response. The results of the present study would help in the creation of a therapeutic plan and prediction of the clinical course of MP pneumonia in children.
Bread Wheat (Triticum aestivum) Responses to Arbuscular Mycorrhizae Inoculation under Drought Stress Conditions
Authors: Abdi Neila , van Biljon Angeline , Steyn Chrisna , Labuschagne Maryke Tine
Published: August 2021

Abiotic constraints such as water deficit reduce cereal production. Plants have different strategies against these stresses to improve plant growth, physiological metabolism and crop production. For example, arbuscular mycorrhiza (AM)—bread wheat association has been shown to improve tolerance to drought stress conditions. The objective of this study was to determine the effect of AM inoculation on plant characteristics, lipid peroxidation, solute accumulation, water deficit saturation, photosynthetic activity, total phenol secretion and enzymatic activities including peroxidise (PO) and polyphenol oxidase (PPO) in two bread wheat cultivars (PAN3497 and SST806) under well-watered and drought-stressed conditions in plants grown under greenhouse conditions, to determine whether AM can enhance drought tolerance in wheat. AM inoculation improved morphological and physiological parameters in plants under stress. The leaf number increased by 35% and 5%, tiller number by 25% and 23%, chlorophyll content by 7% and 10%, accumulation of soluble sugars by 33% and 14%, electrolyte leakage by 26% and 32%, PPO by 44% and 47% and PO by 30% and 37% respectively, in PAN3497 and SST806, respectively. However, drought stress decreased proline content by 20% and 24%, oxidative damage to lipids measured as malondialdehyde by 34% and 60%, and total phenol content by 55% and 40% respectively, in AM treated plants of PAN3497 and SST806. PAN3497 was generally more drought-sensitive than SST806. This study showed that AM can contribute to protect plants against drought stress by alleviating water deficit induced oxidative stress.
The In Vitro and In Vivo Synergistic Antimicrobial Activity Assessment of Vacuum Microwave Assisted Aqueous Extracts from Pomegranate and Avocado Fruit Peels and Avocado Seeds Based on a Mixtures Design Model
Authors: Skenderidis Prodromos , Leontopoulos Stefanos , Petrotos Konstantinos , Mitsagga Chrysanthi , Giavasis Ioannis
Published: August 2021

The present study aimed to assess the antimicrobial properties of encapsulated lyophilized powdered extracts of pomegranate peels (PP), avocado peels (AP) and avocado seeds (AS) in vitro and in vivo. Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) methods, optical density measurement, and well diffusion assay were used to determine antimicrobial activity against food borne bacteria (Gram− Escherichia coli, Salmonella typhimurium, Campylobacter jejuni, Pseudomonas putida), (Gram+ Staphylococcus aureus, Listeria monocytogenes, Clostridium perfringens, Lactobacillus plantarum), and fungi (Penicillium expansum and Aspergillus niger) based on a mixture design model. Additionally, the most effective powder was studied in vivo in yogurt, cream cheese, and minced meat burger. The samples that contained high polyphenol content also exhibited higher antioxidant, antimicrobial, and antifungal activity. From the results of the well diffusion, the MIC/MBC, and the cell optical density assays, the antimicrobial activity of the extracts was found to be correlated to the total phenolic content (TPC) of the samples and the type of the microorganism. The pomegranate peels extract presented the higher TPC and antioxidant activity and constitute the highest percentage in the most active antimicrobial mixture. The powders that were tested in vitro showed microbial type-dependent effects in each food model. The results presented here can be further studied in the large-scale industrial production of natural food preservatives.
Reintroducing Flax (Linum usitatissimum L.) to the Mediterranean Basin: The Importance of Nitrogen Fertilization
Authors: Kakabouki Ioanna , Mavroeidis Antonios , Tataridas Alexandros , Roussis Ioannis , Katsenios Nikolaos , Efthimiadou Aspasia , Tigka Evangelia L. , Karydogianni Stella , Zisi Charikleia , Folina Antigolena , Bilalis Dimitrios
Published: August 2021

An increasing interest has been reported regarding the reintroduction of flax in the Mediterranean region. The aim of this present study was to evaluate the effects of nitrogen (N) fertilization on the performance of flax cv. Everest, under Mediterranean climate conditions. A two-year study was carried out in 2018–2019, in Western Greece. The experiment was set-up in a randomized complete block design with four replications and six treatments of different N fertilization rates (0, 20, 30, 40, 50, and 60 kg N ha−1). Measurements included plant biomass, the leaf area index (LAI), the yield, and the Growth Degree Days (GDDs) required for full seed maturity. The N uptake of flax was also evaluated utilizing the Nitrogen Harvesting (NHI) and Nitrogen Utilization Efficiency (NUtE) indices. Although the highest fertilization rate (60N) increased the yield by 35.4% (2018) and 23.1% (2019), a GDDs and N indices assessment revealed that it noted the lowest efficiency and may lead to significant yield losses, as it significantly prolonged the crop cycle. On the contrary, even though fertilization rates of 20 and 30 kg N ha−1 increased the yield only by 7% and 15% (on average), they were more efficient, and prolonged the crop cycle less (compared to 60N).
Adaboost Algorithm in Artificial Intelligence for Optimizing the IRI Prediction Accuracy of Asphalt Concrete Pavement
Authors: Wang Changbai , Xu Shuzhan , Yang Junxin
Published: August 2021

The international roughness index (IRI) for roads is a crucial pavement design criterion in the Mechanistic-Empirical Pavement Design Guide (MEPDG). However, studies have shown that the IRI transfer function in the MEPDG is simply a linear combination of road parameters, so it cannot provide accurate predictions. To solve this issue, this research developed an AdaBoost regression (ABR) model to improve the prediction ability of IRI and compared it with the linear regression (LR) in MEPDG. The development of the ABR model is based on the Python programming language, using the 4265 records from the Long-Term Pavement Performance (LTPP) that include the pavement thickness, service age, average annual daily truck traffic (AADTT), gator cracks, etc., which are reliable data that are preserved after years of monitoring. The results reveal that the ABR model is significantly better than the LR because the correlation coefficient (R2) between the measured and predicted values in the testing set increased from 0.5118 to 0.9751, and the mean square error (MSE) decreased from 0.0245 to 0.0088. By analyzing the importance of variables, there are many additional crucial factors, such as raveling and bleeding, that affect IRI, which leads to the weak performance of the LR model.
On the Viability of Video Imaging in Leak Rate Quantification: A Theoretical Error Analysis
Authors: Montazeri Amir , Zhou Xiaochi , Albertson John D.
Published: August 2021

Optical gas imaging through multispectral cameras is a promising technique for mitigation of methane emissions through localization and quantification of emissions sources. While more advanced cameras developed in recent years have led to lower uncertainties in measuring gas concentrations, a systematic analysis of the uncertainties associated with leak rate estimation have been overlooked. We present a systematic categorization of the involved uncertainties with a focus on a theoretical analysis of projection uncertainties that are inherent to this technique. The projection uncertainties are then quantified using Large Eddy Simulation experiments of a point source release into the atmosphere. Our results show that while projection uncertainties are typically about 5% of the emission rate, low acquisition times and observation of the gas plume at small distances from the emission source (<10 m) can amount to errors of about 20%. Further, we found that acquisition times on the order of tens of seconds are sufficient to significantly reduce (>50%) the projection uncertainties. These findings suggest robust procedures on how to reduce projection uncertainties, however, a balance between other sources of uncertainty due to operational conditions and the employed instrumentation are required to outline more practical guidelines.