bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats
Authors: Pun Chon Kit , Huang Hui-Chun , Chang Ching-Chih , Chuang Chiao-Lin , Yen Chun-Hsien , Hsu Shao-Jung , Lee Fa-Yauh , Hou Ming-Chih , Huang Yi-Hsiang
Published: July 2021

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.
FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo
Authors: Credendino Sara , De Menna Marta , Cantone Irene , Moccia Carmen , Esposito Matteo , Di Guida Luigi , De Felice Mario , De Vita Gabriella
Published: July 2021

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.
The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update
Authors: Azar Joseph , Bahmad Hisham F. , Daher Darine , Moubarak Maya M. , Hadadeh Ola , Monzer Alissar , Al Bitar Samar , Jamal Mohamed , Al-Sayegh Mohamed , Abou-Kheir Wassim
Published: July 2021

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.
Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?
Authors: Munawar Nayla , Ahsan Khansa , Muhammad Khalid , Ahmad Aftab , Anwar Munir A. , Shah Iltaf , Al Ameri Ahlam Khalifa , Al Mughairbi Fadwa
Published: July 2021

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively determined. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiology of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and production of postbiotics. Gut microbially produced molecules may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiology of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.
Experimental and Theoretical Studies of Dissociative Electron Attachment to Metabolites Oxaloacetic and Citric Acids
Authors: Kopyra Janina , Wierzbicka Paulina , Tulwin Adrian , Thiam Guillaume , Bald Ilko , Rabilloud Franck , Abdoul-Carime Hassan
Published: July 2021

In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3–9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.
Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA
Authors: Herbert Alan , Karapetyan Sergey , Poptsova Maria , Vasquez Karen M. , Vicens Quentin , Vögeli Beat
Published: July 2021

It is now difficult to believe that a biological function for the left-handed Z-DNA and Z-RNA conformations was once controversial. The papers in this Special Issue, “Z-DNA and Z-RNA: from Physical Structure to Biological Function”, are based on presentations at the ABZ2021 meeting that was held virtually on 19 May 2021 and provide evidence for several biological functions of these structures. The first of its kind, this international conference gathered over 200 scientists from many disciplines to specifically address progress in research involving Z-DNA and Z-RNA. These high-energy left-handed conformers of B-DNA and A-RNA are associated with biological functions and disease outcomes, as evidenced from both mouse and human genetic studies. These alternative structures, referred to as “flipons”, form under physiological conditions, regulate type I interferon responses and induce necroptosis during viral infection. They can also stimulate genetic instability, resulting in adaptive evolution and diseases such as cancer. The meeting featured cutting-edge science that was, for the most part, unpublished. We plan for the ABZ meeting to reconvene in 2022.
Tuning Beforehand: A Foresight on RNA Interference (RNAi) and In Vitro-Derived dsRNAs to Enhance Crop Resilience to Biotic and Abiotic Stresses
Authors: Abdellatef Eltayb , Kamal Nasrein Mohamed , Tsujimoto Hisashi
Published: July 2021

Crop yield is severely affected by biotic and abiotic stresses. Plants adapt to these stresses mainly through gene expression reprogramming at the transcriptional and post-transcriptional levels. Recently, the exogenous application of double-stranded RNAs (dsRNAs) and RNA interference (RNAi) technology has emerged as a sustainable and publicly acceptable alternative to genetic transformation, hence, small RNAs (micro-RNAs and small interfering RNAs) have an important role in combating biotic and abiotic stresses in plants. RNAi limits the transcript level by either suppressing transcription (transcriptional gene silencing) or activating sequence-specific RNA degradation (post-transcriptional gene silencing). Using RNAi tools and their respective targets in abiotic stress responses in many crops is well documented. Many miRNAs families are reported in plant tolerance response or adaptation to drought, salinity, and temperature stresses. In biotic stress, the spray-induced gene silencing (SIGS) provides an intelligent method of using dsRNA as a trigger to silence target genes in pests and pathogens without producing side effects such as those caused by chemical pesticides. In this review, we focus on the potential of SIGS as the most recent application of RNAi in agriculture and point out the trends, challenges, and risks of production technologies. Additionally, we provide insights into the potential applications of exogenous RNAi against biotic stresses. We also review the current status of RNAi/miRNA tools and their respective targets on abiotic stress and the most common responsive miRNA families triggered by stress conditions in different crop species.
Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer’s Disease
Authors: Kim Namdoo , Lee Hyuck Jin
Published: July 2021

Redox-active metal ions, Cu(I/II) and Fe(II/III), are essential biological molecules for the normal functioning of the brain, including oxidative metabolism, synaptic plasticity, myelination, and generation of neurotransmitters. Dyshomeostasis of these redox-active metal ions in the brain could cause Alzheimer’s disease (AD). Thus, regulating the levels of Cu(I/II) and Fe(II/III) is necessary for normal brain function. To control the amounts of metal ions in the brain and understand the involvement of Cu(I/II) and Fe(II/III) in the pathogenesis of AD, many chemical agents have been developed. In addition, since toxic aggregates of amyloid-β (Aβ) have been proposed as one of the major causes of the disease, the mechanism of clearing Aβ is also required to be investigated to reveal the etiology of AD clearly. Multiple metalloenzymes (e.g., neprilysin, insulin-degrading enzyme, and ADAM10) have been reported to have an important role in the degradation of Aβ in the brain. These amyloid degrading enzymes (ADE) could interact with redox-active metal ions and affect the pathogenesis of AD. In this review, we introduce and summarize the roles, distributions, and transportations of Cu(I/II) and Fe(II/III), along with previously invented chelators, and the structures and functions of ADE in the brain, as well as their interrelationships.
Impact of Long-Term Enzyme Replacement Therapy on Glucosylsphingosine (Lyso-Gb1) Values in Patients with Type 1 Gaucher Disease: Statistical Models for Comparing Three Enzymatic Formulations
Authors: Dinur Tama , Grittner Ulrike , Revel-Vilk Shoshana , Becker-Cohen Michal , Istaiti Majdolen , Cozma Claudia , Rolfs Arndt , Zimran Ari
Published: July 2021

For three decades, enzyme replacement therapy (ERT), and more recently, substrate reduction therapy, have been the standard-of-care for type I Gaucher disease (GD1). Since 2012, three different ERTs have been available. No clinical trial or academic study has ever compared these ERTs beyond one year. Herein we compare the impact of the ERTs on repeated measurements of glucosylsphingosine (lyso-Gb1; the most sensitive and GD-specific biomarker). A total of 135 adult patients (77 (57%) female) with GD1, followed from July 2014 to March 2020 and treated with a single ERT (imiglucerase (n = 41, 30.4%), taliglucerase alfa (n = 21, 15.6%) and velaglucerase alfa (n = 73, 54.1%)), were included. Disease severity was defined by genotypes (mild: N370S (c.1226A>G) homozygous and N370S/R496H (c.1604G) compound heterozygous; severe: all other genotypes) and by the severity score index (SSI; mild: <7; severe: ≥7). Lyso-Gb1 testing was performed at Centogene™ on dry blood spot samples collected during routine visits. Patients treated with imiglucerase had higher lyso-Gb1 levels at different time points. A huge variation in lyso-Gb1 levels was noticeable both inter-individually and intra-individually for all three ERTs. A steeper and faster decrease of lyso-Gb1 levels was shown in velaglucerase alfa. Nevertheless, the differences between medications were not very large, and bigger numbers and more pretreatment data are required for more powerful conclusions.
Biocompatibility of Lithium Disilicate and Zirconium Oxide Ceramics with Different Surface Topographies for Dental Implant Abutments
Authors: Jung Susanne , Moser Marco Maria , Kleinheinz Johannes , Happe Arndt
Published: July 2021

Gingivafibroblasts were cultured on lithium disilicate, on zirconia dioxide, and on titanium with two different surface roughnesses (0.2 µm and 0.07 µm); Proliferation (MTT), Living/Dead staining, cytotoxicity (LDH), proliferation (FGF2), and inflammation (TNFα) were analyzed after 1 day and 21 days. Furthermore, alteration in cell morphology (SEM) was analyzed. The statistical analysis was performed by a Kruskal–Wallis test. The level of significance was set at p < 0.05. There were no distinct differences in cellular behavior between the tested roughness. There were slight differences between tested materials. Cells grown on zirconia dioxide showed higher cytotoxic effects. Cells grown on lithium disilicate showed less expression of TNFα compared to those grown on zirconia dioxide or titanium. These effects persisted only during the first time span. The results indicate that the two tested high-strength ceramics and surface properties are biologically suitable for transmucosal implant components. The findings may help clinicians to choose the most appropriate biomaterial as well as the most appropriate surface treatment to use in accordance with specific clinical dental applications.
Genome-Wide Identification and Expression Analysis of Tomato ADK Gene Family during Development and Stress
Authors: Yang Lu , Cao Haohao , Zhang Xiaoping , Gui Liangxian , Chen Qiang , Qian Gui , Xiao Jiaxin , Li Zhengguo
Published: July 2021

Adenylate kinase (ADK) is widely distributed in organisms and plays an important role in cellular energy homeostasis. In plants, ADK has important functions in plant growth and development regulation as well as in adaptation to the environment. However, little information is available about the ADK genes in tomato (Solanum lycopersicum), an important economic crop. To investigate the characteristics and functions of ADK genes in tomato, a total of 11 ADK genes were identified and named according to their chromosomal locations. The ADK family in Arabidopsis, tomato, potato, and rice was divided into six groups, and motif analysis revealed that each SlADK protein contained five to eight conserved motifs. A total of 4 to 19 exons were identified in tomato ADK gene family members, and interestingly, most members possessed 4 exons. Several stress response elements were identified in the promoter regions of SlADKs. The 11 SlADKs were randomly distributed on 9 of the 12 tomato chromosomes. Three duplication events were observed between tomato chromosomes, and a high degree of conservation of synteny was demonstrated between tomato and potato. The online TomExpress platform prediction revealed that SlADKs were expressed in various tissues and organs, basically consistent with the data obtained from real-time quantitative PCR (qPCR). The qPCR verification was also performed to determine the expression level of SlADKs and demonstrated that the genes responded to multiple abiotic stresses, such as drought, salt, and cold. Besides, the qPCR results showed that SlADK transcription was responsive to most of the applied hormone treatment. For correlation network analysis under 44 global conditions, the results showed that the number of 17, 3, 4, and 6 coexpressed genes matched with SlADK5, 8, 9, and 11, respectively. For specific gene function analysis, expression of SlADK10 was inhibited using virus-induced gene silencing (VIGS). Compared to wild-type plants, plants with silenced SlADK10 gene had poor drought resistance, indicating SlADK10 regulated drought tolerance of tomato positively. In summary, the information provided in the present study will be helpful to understand the evolutionary relationship and their roles of tomato ADK gene family in further research.
Proteomic Determination of Low-Molecular-Weight Glutenin Subunit Composition in Aroona Near-Isogenic Lines and Standard Wheat Cultivars
Authors: Cho Kyoungwon , Jang You-Ran , Lim Sun-Hyung , Altenbach Susan B. , Gu Yong Q. , Simon-Buss Annamaria , Lee Jong-Yeol
Published: July 2021

The low-molecular weight glutenin subunit (LMW-GS) composition of wheat (Triticum aestivum) flour has important effects on end-use quality. However, assessing the contributions of each LMW-GS to flour quality remains challenging because of the complex LMW-GS composition and allelic variation among wheat cultivars. Therefore, accurate and reliable determination of LMW-GS alleles in germplasm remains an important challenge for wheat breeding. In this study, we used an optimized reversed-phase HPLC method and proteomics approach comprising 2-D gels coupled with liquid chromatography–tandem mass spectrometry (MS/MS) to discriminate individual LMW-GSs corresponding to alleles encoded by the Glu-A3, Glu-B3, and Glu-D3 loci in the ‘Aroona’ cultivar and 12 ‘Aroona’ near-isogenic lines (ARILs), which contain unique LMW-GS alleles in the same genetic background. The LMW-GS separation patterns for ‘Aroona’ and ARILs on chromatograms and 2-D gels were consistent with those from a set of 10 standard wheat cultivars for Glu-3. Furthermore, 12 previously uncharacterized spots in ‘Aroona’ and ARILs were excised from 2-D gels, digested with chymotrypsin, and subjected to MS/MS. We identified their gene haplotypes and created a 2-D gel map of LMW-GS alleles in the germplasm for breeding and screening for desirable LMW-GS alleles for wheat quality improvement.
Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases
Authors: Formichi Caterina , Nigi Laura , Grieco Giuseppina Emanuela , Maccora Carla , Fignani Daniela , Brusco Noemi , Licata Giada , Sebastiani Guido , Dotta Francesco
Published: July 2021

The rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application.
Beneficial Features of Biochar and Arbuscular Mycorrhiza for Improving Spinach Plant Growth, Root Morphological Traits, Physiological Properties, and Soil Enzymatic Activities
Authors: Jabborova Dilfuza , Annapurna Kannepalli , Paul Sangeeta , Kumar Sudhir , Saad Hosam A. , Desouky Said , Ibrahim Mohamed F. M. , Elkelish Amr
Published: July 2021

Biochar and arbuscular mycorrhizal fungi (AMF) can promote plant growth, improve soil properties, and maintain microbial activity. The effects of biochar and AMF on plant growth, root morphological traits, physiological properties, and soil enzymatic activities were studied in spinach (Spinacia oleracea L.). A pot experiment was conducted to evaluate the effect of biochar and AMF on the growth of spinach. Four treatments, a T1 control (soil without biochar), T2 biochar alone, T3 AMF alone, and T4 biochar and AMF together, were arranged in a randomized complete block design with five replications. The biochar alone had a positive effect on the growth of spinach, root morphological traits, physiological properties, and soil enzymatic activities. It significantly increased the plant growth parameters, such as the shoot length, leaf number, leaf length, leaf width, shoot fresh weight, and shoot dry weight. The root morphological traits, plant physiological attributes, and soil enzymatic activities were significantly enhanced with the biochar alone compared with the control. However, the combination of biochar and AMF had a greater impact on the increase in plant growth, root morphological traits, physiological properties, and soil enzymatic activities compared with the other treatments. The results suggested that the combined biochar and AMF led to the highest levels of spinach plant growth, microbial biomass, and soil enzymatic activity.
Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension
Authors: Yang Qunhui , Hori Masatoshi
Published: July 2021

Hypertension is a key risk factor for cardiovascular disease and it is a growing public health problem worldwide. The pathophysiological mechanisms of vascular smooth muscle (VSM) contraction contribute to the development of hypertension. Calcium (Ca2+)-dependent and -independent signaling mechanisms regulate the balance of the myosin light chain kinase and myosin light chain phosphatase to induce myosin phosphorylation, which activates VSM contraction to control blood pressure (BP). Here, we discuss the mechanism of the contractile machinery in VSM, especially RhoA/Rho kinase and PKC/CPI-17 of Ca2+ sensitization pathway in hypertension. The two signaling pathways affect BP in physiological and pathophysiological conditions and are highlighted in pulmonary, pregnancy, and salt-sensitive hypertension.
The Role of Protein S-Nitrosylation in Protein Misfolding-Associated Diseases
Authors: Ju Yun-Jin , Lee Hye-Won , Choi Ji-Woong , Choi Min-Sik
Published: July 2021

Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.
Synthesis of Aminopropyltriethoxysilyl-Substituted Imines and Amides
Authors: Banks Surya R. , Morningstar J. Tanner , Welker Mark E.
Published: July 2021

A series of small molecules containing aminopropyltriethoxysilyl-substituted imines and amides were synthesized so that they could potentially be incorporated into self-assembled monolayers (SAMs) on metal oxide surfaces. Simple one-step imine preparations and two-step amide preparations are reported here.
Peculiarities of DRX in a Highly-Alloyed Austenitic Stainless Steel
Authors: Dolzhenko Pavel , Tikhonova Marina , Kaibyshev Rustam , Belyakov Andrey
Published: July 2021

The features of discontinuous dynamic recrystallization (DRX) in a highly-alloyed austenitic stainless steel were studied at temperatures of 800 °C to 1100 °C. Hot deformation accompanied by DRX was characterized by an activation energy of 415 kJ/mol. The frequency of the sequential DRX cycles depended on the deformation conditions; and the largest fraction of DRX grains with small grain orientation spread below 1° was observed at a temperature of around 1000 °C and a strain rate of about 10−3 s−1. The following power law relationships were obtained for DRX grain size (DDRX) and dislocation density (ρ) vs. temperature-compensated strain rate (Z) or peak flow stress (σP): DDRX ~ Z−0.25, ρ ~ Z0.1, σP ~ DDRX−0.9, σP ~ ρ1.4. The latter, i.e., σP ~ ρ1.4, was valid in the flow stress range below 300 MPa and changed to σP ~ ρ0.5 on increasing the stress. The obtained dependencies suggest a unique power law function between the dislocation density and the DRX grain size with an exponent of −0.5.
Changes in Rheological Properties of Mortars with Steel Slags and Steel Fibers by Magnetic Field
Authors: Kang Dukman , Moon Doyoung , Kim Wooseok
Published: July 2021

The effect of a magnetic field on the rheology of mortars with steel slags and fibers was evaluated in this study. The rheology of the mortar measured with and without a magnetic field was compared. The effect of steel fiber addition to normal and steel slag mortars, mix ratio and size of steel fibers, and magnetic field formation position on rheology were evaluated. Steel fiber addition increased the yield stress and viscosity of the normal and steel slag mortars. The increased rheology was almost restored because of the magnetic field applied to the normal mortars. However, the increased rheology of the steel slag mortars with steel fibers was restored only upon the application of the magnetic field, whose position was continuously changed by a power relay. It is deduced that the alignment of the steel fibers by the magnetic field contributes to the rheology reduction of the mortars. However, in the case of steel slag mortar, experimental results demonstrated that steel slag, which is a ferromagnetic material, receives constant force by the magnetic field, which increases the rheology. This is evidenced by the decrease in the rheology of steel slag mortars under a continuously changing magnetic field formation position by power relay.
Analysis on the Seismic Performance of Steel Fiber-Reinforced High-Strength Concrete Beam–Column Joints
Authors: Shi Ke , Zhang Mengyue , Zhang Tao , Xue Ru , Li Pengfei
Published: July 2021

The present research study aims to investigate numerically the behavior of steel fiber-reinforced high-strength concrete (SFRHC) beam–column joints (BCJs) under seismic action. Based on the plastic damage constitutive model of concrete and elastic–plastic mixed-strengthen constitutive model of steel material, the finite element software ABAQUS was utilized to establish the 3D finite element (FE) model of BCJs. Additionally, the feasibility and accuracy of the numerical simulation were verified by comparing the computed results and experimental observations in terms of the hysteresis curves, skeleton curves, and failure mode. Furthermore, based on the validated FE modeling approach, load vs. displacement hysteresis curves of SFRHC–BCJs during the loading process were analyzed in detail; the failure process was also investigated. Furthermore, the effect of various parameters on the seismic behavior of BCJs was analyzed comprehensively, including the concrete strength, the volume ratio of steel fiber, and the stirrup ratio in the core area. Finally, parametric studies illustrated that increasing the concrete strength helps in enhancing the ultimate load, while the ductility decreased noticeably. Both adding the steel fiber and increasing the stirrup ratio can significantly improve the seismic performance of BCJs.
Self-Healable Biocomposites Crosslinked with a Combination of Silica and Quercetin
Authors: Olejnik Olga , Masek Anna , Szynkowska-Jóźwik Małgorzata Iwona
Published: July 2021

In this publication, novel bio-based composites made of epoxidized natural rubber with 50 mol% of epoxidation (ENR-50) are presented. The obtained materials, partially cured with a totally environmentally friendly crosslinking system consisting of natural ingredients, including quercetin and silica, exhibit a self-healing ability resulting from the self-adhesion of ENR-50 and reversible physical forces between the curing agent and the matrix. The impact of natural components on the crosslinking effect in uncured ENR-50 matrix was analyzed based on rheometric measurements, mechanical tests and crosslinking density. The partially crosslinked samples were next cut into two separate pieces, which were instantly contacted together under a small manual press, left at room temperature for a few days for the healing process to occur and finally retested. The healing efficiency was estimated by measuring mechanical properties before and after the healing process and was also confirmed by photos taken using optical and scanning electron microscope (SEM). According to the results, a combination of silica and quercetin is a totally safe, natural and effective crosslinking system dedicated to epoxidized natural rubber. The novel composites containing ingredients safe for human beings exhibit promising self-healing properties with a healing efficiency of up to 45% without any external stimuli and stand a chance of becoming innovative biomedical materials.
Revised Model of Abrasive Water Jet Cutting for Industrial Use
Authors: Hlaváč Libor M.
Published: July 2021

Research performed by the author in the last decade led him to a revision of his older analytical models used for a description and evaluation of abrasive water jet (AWJ) cutting. The review has shown that the power of 1.5 selected for the traverse speed thirty years ago was influenced by the precision of measuring devices. Therefore, the correlation of results calculated from a theoretical model with the results of experiments performed then led to an increasing of the traverse speed exponent above the value derived from the theoretical base. Contemporary measurements, with more precise devices, show that the power suitable for the traverse speed is essentially the same as the value derived in the theoretical description, i.e., it is equal to “one”. Simultaneously, the replacement of the diameter of the water nozzle (orifice) by the focusing (abrasive) tube diameter in the respective equations has been discussed, because this factor is very important for the AWJ machining. Some applications of the revised model are presented and discussed, particularly the reduced forms for a quick recalculation of the changed conditions. The correlation seems to be very good for the results calculated from the present model and those determined from experiments. The improved model shows potential to be a significant tool for preparation of the control software with higher precision in determination of results and higher calculation speed.
A Case of Incidental Schwannoma Mimicking Necrotic Metastatic Lymph Node from Bladder Cancer
Authors: Choi Jeong-Hyouk , Yoo Koo-Han , Lee Dong-Gi , Min Gyeong-Eun , Kim Gou-Young , Choi Tae-Soo
Published: July 2021

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.
Burn Injury: Mechanisms of Keratinocyte Cell Death
Authors: Rennekampff Hans-Oliver , Alharbi Ziyad
Published: July 2021

Cutaneous burn injury is associated with epidermal loss in the zone of coagulation zone and delayed tissue loss in the zone of stasis. Thus, thermal stress can trigger both necrosis and regulated cell death (RCD) or apoptosis. Experimental in vitro and in vivo work has clearly demonstrated apoptotic events of thermally injured keratinocytes that are accompanied by morphological and biochemical markers of regulated cell death. However, in vivo data for the different pathways of regulated cell death are sparse. In vitro experiments with heat-stressed human keratinocytes have demonstrated death receptor involvement (extrinsic apoptosis), calcium influx, and disruption of mitochondrial membrane potential (intrinsic apoptosis) in regulated cell death. In addition, caspase-independent pathways have been suggested in regulated cell death. Keratinocyte heat stress leads to reduced proliferation, possibly as a result of reduced keratinocyte adhesion (anoikis) or oncogene involvement. Understanding the underlying mechanisms of RCD and the skin’s responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma.
Doxycycline Interferes with Zika Virus Serine Protease and Inhibits Virus Replication in Human Skin Fibroblasts
Authors: Chong Teoh Teow , J. Al-Harbi Sawsam , Abdulrahman Ammar Yasir , Rothan Hussin A.
Published: July 2021

Zika virus (ZIKV) represents a re-emerging threat to global health due to its association with congenital birth defects. ZIKV NS2B-NS3 protease is crucial for virus replication by cleaving viral polyprotein at various junctions to release viral proteins and cause cytotoxic effects in ZIKV-infected cells. This study characterized the inhibitory effects of doxycycline against ZIKV NS2B-NS3 protease and viral replication in human skin cells. The in silico data showed that doxycycline binds to the active site of ZIKV protease at a low docking energy (−7.8 Kcal/mol) via four hydrogen bonds with the protease residues TYR1130, SER1135, GLY1151, and ASP83. Doxycycline efficiently inhibited viral NS2B-NS3 protease at average human temperature (37 °C) and human temperature with a high fever during virus infection (40 °C). Interestingly, doxycycline showed a higher inhibitory effect at 40 °C (IC50 = 5.3 µM) compared to 37 °C (9.9 µM). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 µM of doxycycline. Treatment with 20 µM of doxycycline reduced the cytopathic effects (CPE), and the 40 µM of doxycycline almost eliminated the CPE of human skin cells. This study showed that doxycycline binds to the ZIKV protease and inhibits its catalytic activity at a low micro-molecular concentration range. Treatment of human skin fibroblast with doxycycline eliminated ZIKV infection and protected the cells against the cytopathic effects of the infection.
Search for Novel Lead Inhibitors of Yeast Cytochrome bc1, from Drugbank and COCONUT
Authors: Jović Ozren , Šmuc Tomislav
Published: July 2021

In this work we introduce a novel filtering and molecular modeling pipeline based on a fingerprint and descriptor similarity procedure, coupled with molecular docking and molecular dynamics (MD), to select potential novel quoinone outside inhibitors (QoI) of cytochrome bc1 with the aim of determining the same or different chromophores to usual. The study was carried out using the yeast cytochrome bc1 complex with its docked ligand (stigmatellin), using all the fungicides from FRAC code C3 mode of action, 8617 Drugbank compounds and 401,624 COCONUT compounds. The introduced drug repurposing pipeline consists of compound similarity with C3 fungicides and molecular docking (MD) simulations with final QM/MM binding energy determination, while aiming for potential novel chromophores and perserving at least an amide (R1HN(C=O)R2) or ester functional group of almost all up to date C3 fungicides. 3D descriptors used for a similarity test were based on the 280 most stable Padel descriptors. Hit compounds that passed fingerprint and 3D descriptor similarity condition and had either an amide or an ester group were submitted to docking where they further had to satisfy both Chemscore fitness and specific conformation constraints. This rigorous selection resulted in a very limited number of candidates that were forwarded to MD simulations and QM/MM binding affinity estimations by the ORCA DFT program. In this final step, stringent criteria based on (a) sufficiently high frequency of H-bonds; (b) high interaction energy between protein and ligand through the whole MD trajectory; and (c) high enough QM/MM binding energy scores were applied to further filter candidate inhibitors. This elaborate search pipeline led finaly to four Drugbank synthetic lead compounds (DrugBank) and seven natural (COCONUT database) lead compounds—tentative new inhibitors of cytochrome bc1. These eleven lead compounds were additionally validated through a comparison of MM/PBSA free binding energy for new leads against those obtatined for 19 QoIs.
Plants Secondary Metabolites as Blood Glucose-Lowering Molecules
Authors: Shehadeh Mayadah Bashir , Suaifan Ghadeer A. R. Y. , Abu-Odeh Ala’ Mustafa
Published: July 2021

Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants’ secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics.
A Review of Ladybug Taint in Wine: Origins, Prevention, and Remediation
Authors: Pickering Gary J. , Botezatu Andreea
Published: July 2021

Ladybug taint (also known as ladybird taint) is a relatively recently recognized fault that has been identified in wines from a wide range of terroirs. Alkyl-methoxypyrazines—particularly 2-isopropyl-3-methoxypyrazine—have been determined as the causal compounds, and these are introduced into grape must during processing, when specific species of vineyard-dwelling Coccinellidae are incorporated into the harvested fruit. Coccinella septempunctata, and especially the invasive Harmonia axyridis, are the beetles implicated, and climate change is facilitating wider dispersal and survivability of H. axyridis in viticultural regions worldwide. Affected wines are typically characterized as possessing excessively green, bell pepper-, and peanut-like aroma and flavor. In this paper, we review a range of vineyard practices that seek to reduce Coccinellidae densities, as well as both “standard” and novel wine treatments aimed at reducing alkyl-methoxypyrazine load. We conclude that while prevention of ladybug taint is preferable, there are several winery interventions that can remediate the quality of wine affected by this taint, although they vary in their relative efficacy and specificity.
Bioguided Isolation of Active Compounds from Rhamnus alaternus against Methicillin-Resistant Staphylococcus aureus (MRSA) and Panton-Valentine Leucocidin Positive Strains (MSSA-PVL)
Authors: Zeouk Ikrame , Ouedrhiri Wessal , Sifaoui Ines , Bazzocchi Isabel L. , Piñero José E. , Jiménez Ignacio A. , Lorenzo-Morales Jacob , Bekhti Khadija
Published: July 2021

Despite intensified efforts to develop an effective antibiotic, S. aureus is still a major cause of mortality and morbidity worldwide. The multidrug resistance of bacteria has considerably increased the difficulties of scientific research and the concomitant emergence of resistance is to be expected. In this study we have investigated the in vitro activity of 15 ethanol extracts prepared from Moroccan medicinal plants traditionally used for treatment of skin infections. Among the tested species I. viscosa, C. oxyacantha, R. tinctorum, A. herba alba, and B. hispanica showed moderate anti-staphylococcal activity. However, R. alaternus showed promising growth-inhibitory effects against specific pathogenic bacteria especially methicillin-susceptible Staphylococcus aureus Panton-Valentine leucocidin positive (MSSA-PVL) and methicillin-resistant S. aureus (MRSA). The bioguided fractionation of this plant using successive chromatographic separations followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) including EIMS and HREIMS analysis yielded the emodin (1) and kaempferol (2). Emodin being the most active with MICs ranging between 15.62 and 1.95 µg/mL and showing higher activity against the tested strains in comparison with the crude extract, its mechanism of action and the structure-activity relationship were interestingly discussed. The active compound has not displayed toxicity toward murine macrophage cells. The results obtained in the current study support the traditional uses of R. alaternus and suggest that this species could be a good source for the development of new anti-staphylococcal agents.
Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family
Authors: Nonga Olivier E. , Lavogina Darja , Enkvist Erki , Kestav Katrin , Chaikuad Apirat , Dixon-Clarke Sarah E. , Bullock Alex N. , Kopanchuk Sergei , Ivan Taavi , Ekambaram Ramesh , Viht Kaido , Knapp Stefan , Uri Asko
Published: July 2021

We performed an X-ray crystallographic study of complexes of protein kinase PIM-1 with three inhibitors comprising an adenosine mimetic moiety, a linker, and a peptide-mimetic (d-Arg)6 fragment. Guided by the structural models, simplified chemical structures with a reduced number of polar groups and chiral centers were designed. The developed inhibitors retained low-nanomolar potency and possessed remarkable selectivity toward the PIM kinases. The new inhibitors were derivatized with biotin or fluorescent dye Cy5 and then applied for the detection of PIM kinases in biochemical solutions and in complex biological samples. The sandwich assay utilizing a PIM-2-selective detection antibody featured a low limit of quantification (44 pg of active recombinant PIM-2). Fluorescent probes were efficiently taken up by U2OS cells and showed a high extent of co-localization with PIM-1 fused with a fluorescent protein. Overall, the developed inhibitors and derivatives represent versatile chemical tools for studying PIM function in cellular systems in normal and disease physiology.
Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
Authors: Paul Alok K. , Gueven Nuri , Dietis Nikolas
Published: July 2021

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.