bluuebunny/crossref_metadata_2025 huggingface dataset:
Implant-Prosthetic Restoration of a Patient with Osteogenesis Imperfecta: A Case Report
Authors: Hanisch Marcel , Maus Melanie , Kleinheinz Johannes
Published: April 2021

Osteogenesis imperfecta describes a group of genetic disorders that result from a defect in collagen type I and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Osteogenesis imperfecta is mostly caused by mutations in the COL1A1 (17q21.33) and COL1A2 (7q21.3) genes. There have only been a few case reports of implant-prosthetic treatment for patients with osteogenesis imperfecta. These reports indicated that implants and augmentation procedures can be implemented in such patients. However, for patients receiving additional antiresorptive therapy, cautious approaches should be chosen and the risk of drug-associated osteonecrosis should be considered. The aim of this article is to report on the implant-prosthetic treatment of a patient with type I osteogenesis imperfecta.
Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment
Authors: Ting Hui-Kung , Chen Chin-Li , Meng En , Cherng Juin-Hong , Chang Shu-Jen , Kao Chien-Chang , Yang Ming-Hsin , Leung Fang-Shiuan , Wu Sheng-Tang
Published: April 2021

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.
TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts
Authors: Kádár Kristóf , Juhász Viktória , Földes Anna , Rácz Róbert , Zhang Yan , Löchli Heike , Kató Erzsébet , Köles László , Steward Martin C. , DenBesten Pamela , Varga Gábor , Zsembery Ákos
Published: April 2021

TRPM7 plays an important role in cellular Ca2+, Zn2+ and Mg2+ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca2+ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg2+ ([Mg2+]i), were reduced by elevated [Mg2+]i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg2+]i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca2+ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca2+ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca2+ uptake and as an independent Ca2+ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca2+ transport in amelogenesis.
Splice Variants of Superoxide Dismutases in Rice and Their Expression Profiles under Abiotic Stresses
Authors: Saini Ajay , Rohila Jai S. , Govindan Ganesan , Li Yong-Fang , Sunkar Ramanjulu
Published: April 2021

The superoxide dismutases (SODs) play vital roles in controlling cellular reactive oxygen species (ROS) that are generated both under optimal as well as stress conditions in plants. The rice genome harbors seven SOD genes (CSD1, CSD2, CSD3, CSD4, FSD1, FSD2, and MSD) that encode seven constitutive transcripts. Of these, five (CSD2, CSD3, CSD4, FSD1, and MSD) utilizes an alternative splicing (AS) strategy and generate seven additional splice variants (SVs) or mRNA variants, i.e., three for CSD3, and one each for CSD2, CSD4, FSD1, and MSD. The exon-intron organization of these SVs revealed variations in the number and length of exons and/or untranslated regions (UTRs). We determined the expression patterns of SVs along with their constitutive forms of SODs in rice seedlings exposed to salt, osmotic, cold, heavy metal (Cu+2) stresses, as well as copper-deprivation. The results revealed that all seven SVs were transcriptionally active in both roots and shoots. When compared to their corresponding constitutive transcripts, the profiles of five SVs were almost similar, while two specific SVs (CSD3-SV4 and MSD-SV2) differed significantly, and the differences were also apparent between shoots and roots suggesting that the specific SVs are likely to play important roles in a tissue-specific and stress-specific manner. Overall, the present study has provided a comprehensive analysis of the SVs of SODs and their responses to stress conditions in shoots and roots of rice seedlings.
Pathophysiological In Vitro Profile of Neuronal Differentiated Cells Derived from Niemann-Pick Disease Type C2 Patient-Specific iPSCs Carrying the NPC2 Mutations c.58G>T/c.140G>T
Authors: Liedtke Maik , Völkner Christin , Jürs Alexandra V. , Peter Franziska , Rabenstein Michael , Hermann Andreas , Frech Moritz J.
Published: April 2021

Niemann-Pick type C2 (NP-C2) disease is a rare hereditary disease caused by mutations in the NPC2 gene. NPC2 is a small, soluble protein consisting of 151 amino acids, primarily expressed in late endosomes and lysosomes (LE/LY). Together with NPC1, a transmembrane protein found in these organelles, NPC2 accomplishes the exclusion of cholesterol; thus, both proteins are essential to maintain cellular cholesterol homeostasis. Consequently, mutations in the NPC2 or NPC1 gene result in pathophysiological accumulation of cholesterol and sphingolipids in LE/LY. The vast majority of Niemann-Pick type C disease patients, 95%, suffer from a mutation of NPC1, and only 5% display a mutation of NPC2. The biochemical phenotype of NP-C1 and NP-C2 appears to be indistinguishable, and both diseases share several commonalities in the clinical manifestation. Studies of the pathological mechanisms underlying NP-C2 are mostly based on NP-C2 animal models and NP-C2 patient-derived fibroblasts. Recently, we established induced pluripotent stem cells (iPSCs), derived from a donor carrying the NPC2 mutations c.58G>T/c.140G>T. Here, we present a profile of pathophysiological in vitro features, shared by NP-C1 and NP-C2, of neural differentiated cells obtained from the patient specific iPSCs. Profiling comprised a determination of the NPC2 protein level, detection of cholesterol accumulation by filipin staining, analysis of oxidative stress, and determination of autophagy. As expected, the NPC2-deficient cells displayed a significantly reduced amount of NPC2 protein, and, accordingly, we observed a significantly increased amount of cholesterol. Most notably, NPC2-deficient cells displayed only a slight increase of reactive oxygen species (ROS), suggesting that they do not suffer from oxidative stress and express catalase at a high level. As a site note, comparable NPC1-deficient cells suffer from a lack of catalase and display an increased level of ROS. In summary, this cell line provides a valuable tool to gain deeper understanding, not only of the pathogenic mechanism of NP-C2, but also of NP-C1.
Disulfiram Abrogates Morphine Tolerance—A Possible Role of µ-Opioid Receptor-Related G-Protein Activation in the Striatum
Authors: de Corde-Skurska Anna , Krzascik Pawel , Lesniak Anna , Sacharczuk Mariusz , Nagraba Lukasz , Bujalska-Zadrozny Magdalena
Published: April 2021

One of the key strategies for effective pain management involves delaying analgesic tolerance. Early clinical reports indicate an extraordinary effectiveness of off-label disulfiram—an agent designed for alcohol use disorder—in potentiating opioid analgesia and abrogation of tolerance. Our study aimed to determine whether sustained µ-opioid signaling upon disulfiram exposure contributes to these phenomena. Wistar rats were exposed to acute and chronic disulfiram and morphine cotreatment. Nociceptive thresholds were assessed with the mechanical Randal-Selitto and thermal tail-flick tests. µ-opioid receptor activation in brain structures important for pain processing was carried out with the [35S]GTPγS assay. The results suggest that disulfiram (12.5–50 mg/kg i.g.) augmented morphine antinociception and diminished morphine (25 mg/kg, i.g.) tolerance in a supraspinal, opioid-dependent manner. Disulfiram (25 mg/kg, i.g.) induced a transient enhancement of µ-opioid receptor activation in the periaqueductal gray matter (PAG), rostral ventromedial medulla (RVM), hypothalamus, prefrontal cortex and the dorsal striatum at day 1 of morphine treatment. Disulfiram rescued µ-opioid receptor signaling in the nucleus accumbens and caudate-putamen 14 days following morphine and disulfiram cotreatment. The results of this study suggest that striatal µ-opioid receptors may contribute to the abolition of morphine tolerance following concomitant treatment with disulfiram.
Ligand-Receptor Interactions and Machine Learning in GCGR and GLP-1R Drug Discovery
Authors: Mizera Mikołaj , Latek Dorota
Published: April 2021

The large amount of data that has been collected so far for G protein-coupled receptors requires machine learning (ML) approaches to fully exploit its potential. Our previous ML model based on gradient boosting used for prediction of drug affinity and selectivity for a receptor subtype was compared with explicit information on ligand-receptor interactions from induced-fit docking. Both methods have proved their usefulness in drug response predictions. Yet, their successful combination still requires allosteric/orthosteric assignment of ligands from datasets. Our ligand datasets included activities of two members of the secretin receptor family: GCGR and GLP-1R. Simultaneous activation of two or three receptors of this family by dual or triple agonists is not a typical kind of information included in compound databases. A precise allosteric/orthosteric ligand assignment requires a continuous update based on new structural and biological data. This data incompleteness remains the main obstacle for current ML methods applied to class B GPCR drug discovery. Even so, for these two class B receptors, our ligand-based ML model demonstrated high accuracy (5-fold cross-validation Q2 > 0.63 and Q2 > 0.67 for GLP-1R and GCGR, respectively). In addition, we performed a ligand annotation using recent cryogenic-electron microscopy (cryo-EM) and X-ray crystallographic data on small-molecule complexes of GCGR and GLP-1R. As a result, we assigned GLP-1R and GCGR actives deposited in ChEMBL to four small-molecule binding sites occupied by positive and negative allosteric modulators and a full agonist. Annotated compounds were added to our recently released repository of GPCR data.
Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7
Authors: Marchese Patrizia , Lombardi Maria , Mantione Maria Elena , Baccellieri Domenico , Ferrara David , Chiesa Roberto , Alfieri Ottavio , Foglieni Chiara
Published: April 2021

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.
MicroRNAs and Long Noncoding RNAs as Novel Therapeutic Targets in Estrogen Receptor-Positive Breast and Ovarian Cancers
Authors: Barwal Tushar Singh , Sharma Uttam , Bazala Sonali , Singh Ipsa , Jain Manju , Prakash Hridayesh , Shekhar Shashank , Sandberg Elise N. , Bishayee Anupam , Jain Aklank
Published: April 2021

Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, β-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment–delivery mechanisms.
Drusenoid Pigment Epithelial Detachment: Genetic and Clinical Characteristics
Authors: Shijo Taiyo , Sakurada Yoichi , Tanaka Koji , Miki Akiko , Yoneyama Seigo , Machida Yumiko , Chubachi Aya , Wakatsuki Yu , Sugiyama Atsushi , Onoe Hajime , Kikushima Wataru , Mori Ryusaburo , Kashiwagi Kenji
Published: April 2021

Few studies report drusenoid pigment epithelial detachment (DPED) in Asians. In this multicenter study, we report the clinical and genetic characteristics of 76 patients with DPED, and, for comparison, 861 patients with exudative age-related macular degeneration (AMD) were included. On the initial presentation, the mean best-corrected visual acuity was 0.087 ± 0.17 (logMAR unit), and mean DPED height and width were 210 ± 132 and 1633 ± 1114 µm, respectively. Fifty-one (67%) patients showed macular neovascularization in the contralateral eye. The risk allele frequency of both ARMS2 A69S and CFH I62V was significantly higher in DPED than in typical AMD and polypoidal choroidal vasculopathy (PCV) (ARMS2 A69S risk allele frequency: DPED 77% vs. typical AMD 66% vs. PCV 57%, CFH I62V risk allele frequency: DPED 87% vs. typical AMD 73% vs. PCV 73%), although the risk allele frequency of both genes was similar between the DPED group and retinal angiomatous proliferation (RAP) group (ARMS2 A69S: p = 0.32, CFH I62V, p = 0.11). The prevalence of reticular pseudodrusen (RPD) was highest in RAP (60%), followed by DPED (22%), typical AMD (20%), and PCV (2%). Although the prevalence of RPD differs between DPED and RAP, these entities share a similar genetic background in terms of ARMS2 and CFH genes.
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine
Authors: Ismail Aram , Lewis Elizabeth , Sjödin Birgitta , Mannervik Bengt
Published: April 2021

Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis lupus familiaris, has merits as a marker for tumors and as a target for enzyme-activated prodrugs. We produced the canine enzyme CluGST P1-1 by heterologous bacterial expression and verified its cross-reactivity with antihuman-GST P1-1 antibodies. The catalytic activity with alternative substrates of biological significance was determined, and the most active substrate found was benzyl isothiocyanate. Among established GST inhibitors, Cibacron Blue showed positive cooperativity with an IC50 value of 43 nM. Dog GST P1-1 catalyzes activation of the prodrug Telcyta, but the activity is significantly lower than that of the human homolog.
Structural Biology for the Molecular Insight between Aptamers and Target Proteins
Authors: Zhang Ning , Chen Zihao , Liu Dingdong , Jiang Hewen , Zhang Zong-Kang , Lu Aiping , Zhang Bao-Ting , Yu Yuanyuan , Zhang Ge
Published: April 2021

Aptamers are promising therapeutic and diagnostic agents for various diseases due to their high affinity and specificity against target proteins. Structural determination in combination with multiple biochemical and biophysical methods could help to explore the interacting mechanism between aptamers and their targets. Regrettably, structural studies for aptamer–target interactions are still the bottleneck in this field, which are facing various difficulties. In this review, we first reviewed the methods for resolving structures of aptamer–protein complexes and for analyzing the interactions between aptamers and target proteins. We summarized the general features of the interacting nucleotides and residues involved in the interactions between aptamers and proteins. Challenges and perspectives in current methodologies were discussed. Approaches for determining the binding affinity between aptamers and target proteins as well as modification strategies for stabilizing the binding affinity of aptamers to target proteins were also reviewed. The review could help to understand how aptamers interact with their targets and how alterations such as chemical modifications in the structures affect the affinity and function of aptamers, which could facilitate the optimization and translation of aptamers-based theranostics.
Putrescine Depletion Affects Arabidopsis Root Meristem Size by Modulating Auxin and Cytokinin Signaling and ROS Accumulation
Authors: Hashem Ahmed M. , Moore Simon , Chen Shangjian , Hu Chenchen , Zhao Qing , Elesawi Ibrahim Eid , Feng Yanni , Topping Jennifer F. , Liu Junli , Lindsey Keith , Chen Chunli
Published: April 2021

Polyamines (PAs) dramatically affect root architecture and development, mainly by unknown mechanisms; however, accumulating evidence points to hormone signaling and reactive oxygen species (ROS) as candidate mechanisms. To test this hypothesis, PA levels were modified by progressively reducing ADC1/2 activity and Put levels, and then changes in root meristematic zone (MZ) size, ROS, and auxin and cytokinin (CK) signaling were investigated. Decreasing putrescine resulted in an interesting inverted-U-trend in primary root growth and a similar trend in MZ size, and differential changes in putrescine (Put), spermidine (Spd), and combined spermine (Spm) plus thermospermine (Tspm) levels. At low Put concentrations, ROS accumulation increased coincidently with decreasing MZ size, and treatment with ROS scavenger KI partially rescued this phenotype. Analysis of double AtrbohD/F loss-of-function mutants indicated that NADPH oxidases were not involved in H2O2 accumulation and that elevated ROS levels were due to changes in PA back-conversion, terminal catabolism, PA ROS scavenging, or another pathway. Decreasing Put resulted in a non-linear trend in auxin signaling, whereas CK signaling decreased, re-balancing auxin and CK signaling. Different levels of Put modulated the expression of PIN1 and PIN2 auxin transporters, indicating changes to auxin distribution. These data strongly suggest that PAs modulate MZ size through both hormone signaling and ROS accumulation in Arabidopsis.
Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases
Authors: Yu Zhongjie , Wang Yashuo , Liu Lili , Zhang Xianjuan , Jiang Shasha , Wang Bin
Published: April 2021

Human cytomegalovirus (HCMV) belongs to the β-herpesvirus family, which is transmitted in almost every part of the world and is carried by more than 90% of the general population. Increasing evidence indicates that HCMV infection triggers numerous diseases by disrupting the normal physiological activity of host cells, particularly apoptosis. Apoptosis disorder plays a key role in the initiation and development of multiple diseases. However, the relationship and molecular mechanism of HCMV-related diseases and apoptosis have not yet been systematically summarized. This review aims to summarize the role of apoptosis in HCMV-related diseases and provide an insight into the molecular mechanism of apoptosis induced by HCMV infection. We summarize the literature on HCMV-related diseases and suggest novel strategies for HCMV treatment by regulating apoptosis.
Consumers’ Adoption and Use of E-Currencies in Virtual Markets in the Context of an Online Game
Authors: Gawron Magdalena , Strzelecki Artur
Published: April 2021

Virtual worlds have created unique economies whose outcome is e-currencies, which link the electronic universe and reality. This article aims to examine how perceived usefulness, perceived ease of use, perceived risks, and perceived trust significantly impact consumers’ virtual currencies’ behaviour. The study tested and used an adapted TAM model in the context of virtual currencies using structural equation modelling. The partial least square method of structural equation modelling is employed to test the proposed research model. The study utilises an online survey to obtain data from 205 virtual currency consumers. The data set was analysed using SmartPLS 3 software. The results showed that the best predictor of consumers’ intention to use virtual currencies is perceived usefulness, followed by perceived ease of use. Perceived trust predicts consumers’ perceived usefulness and perceived ease of use. These findings reveal that virtual currencies are seen as useful and easy to use. Consumers trust them enough but notice the risks they carry. They can also accept problems associated with them when it comes to their intention to use them.
The Emergence of Determiners in French L2 from the Point of View of L1/L2 Comparison
Authors: Watorek Marzena , Trévisiol Pascale , Rast Rebekah
Published: April 2021

The acquisition of determiners in French presents a significant challenge for both children in L1 and adults in L2. Research in L1 acquisition has found that French determiners, which are highly constrained, appear quite early relative to other languages. Using the conversational data of two beginning learners of French—a native speaker of Spanish and a native speaker of Arabic—in a natural setting (comparable to the L1 data), the present study seeks to understand how these constraints affect the acquisition of the determiner system in L2 French. Analyses reveal the following: (1) Unlike French children who produce “fillers” without clear functional distinctions, adults produce idiosyncratic pre-nominal monosyllables that not only fulfil the obligatory position of “determiner” but are also characterized by identifiable functions in terms of definiteness or indefiniteness. (2) Adult learners’ L1s (Spanish and Arabic) influence the acquisition of NP in French L2, as observed in the emergence of determination in the two learners’ productions. (3) Adult learners’ productions provide evidence of shared “language-neutral” processes attested in initial acquisition in a natural setting; these are independent of the L1 and L2 input properties.
Homopiperazine (Hexahydro-1,4-diazepine)
Authors: Aitken R. Alan , Sonecha Dheirya K. , Slawin Alexandra M. Z.
Published: April 2021

The X-ray structure of the title compound has been determined for the first time. Data on its 1H–13C-NMR coupling constants and 15N-NMR spectrum are also given.
Propyl Gallate
Authors: Nguyen Van Hai , Le Minh Ngoc , Nguyen Hoa Binh , Ha Kieu Oanh , Pham Thai Ha Van , Nguyen Thi Hong , Dao Nguyet Suong Huyen , Nguyen Van Giang , Nguyen Dinh Luyen , Trinh Nguyen Trieu
Published: April 2021

The title compound, propyl gallate (III), is an important substance popularly used in the food, cosmetic and pharmaceutical industries. Current chemical syntheses of this compound are based on the acylation supported by thionyl chloride, DIC/DMAP or Fischer esterification using a range of homogenous and heterogenous catalysts. In this paper, an efficient, green, straightforward, and economical method for synthesizing propyl gallate using potassium hydrogen sulfate, KHSO4, as the heterogenous acidic catalyst has been developed for the first time. In addition, this paper provides a comprehensive spectral dataset for the title compound, especially the new data on DEPT and 2D NMR (HSQC and HMBC) spectra which are not currently available in the literature.
A Review of Impact of Textile Research on Protective Face Masks
Authors: Militky Jiri , Novak Ondrej , Kremenakova Dana , Wiener Jakub , Venkataraman Mohanapriya , Zhu Guocheng , Yao Juming , Aneja Arun
Published: April 2021

COVID-19, classified as SARS-CoV-2, is causing an ongoing global pandemic. The pandemic has resulted in the loss of lives and has caused economic hardships. Most of the devices used to protect against the transmission of the novel COVID-19 disease are related to textile structures. Hence, the challenge for textile professionals is to design and develop suitable textile structures with multiple functionalities for capturing viruses, passivating them, and, at the same time, having no adverse effects on humans during the complete period of use. In addition to manufacturing efficient, biocompatible, and cost-effective protective face masks, it is also necessary to inform the public about the benefits and risks of protective face mask materials. The purpose of this article is to address the concerns of efficiency and efficacy of face masks by primarily reviewing the literature of research conducted at the Technical University of Liberec. The main focus is on the presentation of problems related to the specification of aims of face mask applications, mechanisms of capture, durability, and modes of sterilization. The recommendations, instead of conclusions, are addressed to the whole textile society because they should be leading players in the design, creation, and proper treatment of face masks due to their familiarity with the complex behavior of textile structures and targeted changes of structural hierarchy starting from polymeric chains (nano-level) and ending in planar textile structures (millimeter level) due to action by mechanical, physical and chemical fields. This becomes extremely critical to saving hundreds of thousands of lives from COVID-19.
Color-Tunable White LEDs with Single Chip Realized through Phosphor Pattern and Thermal-Modulating Optical Film
Authors: Su Zhenpeng , Zhao Bo , Gong Zheng , Peng Yang , Bai Fan , Zheng Huai , Joo Sang
Published: April 2021

In this paper, a new method to regulate the correlated color temperature (CCT) of white light-emitting diodes (LEDs) is proposed for the single-chip packaging structure, in which the blue light distribution emitted from the chip in the red/yellow phosphor layer was modulated through changing the paraffin-polydimethylsiloxane (PDMS) film transparence and haze. The results show that the transmittance of the paraffin-PDMS film can be modulated from 49.76% to 97.64%, while the haze of that ranges from 88.19% to 63.10%. When the thickness of paraffin-PDMS film is 0.6 mm, and the paraffin-PDMS film concentration is 30 wt%, the CCT of white LED decreases from 15177 K to 3615 K with the increase of thermal load in the paraffin-PDMS film. The modulating range of its CCT reaches 11562 K. The maximum CCT variation at the same test condition is only 536 K in the repeated experiments within one week.
A Literature Review of Hybrid System Dynamics and Agent-Based Modeling in a Produced Water Management Context
Authors: Langarudi Saeed P. , Sabie Robert P. , Bahaddin Babak , Fernald Alexander G.
Published: April 2021

This paper explores the possibility and plausibility of developing a hybrid simulation method combining agent-based (AB) and system dynamics (SD) modeling to address the case study of produced water management (PWM). In southeastern New Mexico, the oil and gas industry generates large volumes of produced water, while at the same time, freshwater resources are scarce. Single-method models are unable to capture the dynamic impacts of PWM on the water budget at both the local and regional levels, hence the need for a more complex hybrid approach. We used the literature, information characterizing produced water in New Mexico, and our preliminary interviews with subject matter experts to develop this framework. We then conducted a systematic literature review to summarize state-of-the-art of hybrid modeling methodologies and techniques. Our research revealed that there is a small but growing volume of hybrid modeling research that could provide some foundational support for modelers interested in hybrid modeling approaches for complex natural resource management issues. We categorized these efforts into four classes based on their approaches to hybrid modeling. It appears that, among these classes, PWM requires the most sophisticated approach, indicating that PWM modelers will need to face serious challenges and break new ground in this realm.
Study of Beryllium, Magnesium, and Spodium Bonds to Carbenes and Carbodiphosphoranes
Authors: Jabłoński Mirosław
Published: April 2021

The aim of this article is to present results of theoretical study on the properties of C⋯M bonds, where C is either a carbene or carbodiphosphorane carbon atom and M is an acidic center of MX2 (M = Be, Mg, Zn). Due to the rarity of theoretical data regarding the C⋯Zn bond (i.e., the zinc bond), the main focus is placed on comparing the characteristics of this interaction with C⋯Be (beryllium bond) and C⋯Mg (magnesium bond). For this purpose, theoretical studies (ωB97X-D/6-311++G(2df,2p)) have been performed for a large group of dimers formed by MX2 (X = H, F, Cl, Br, Me) and either a carbene ((NH2)2C, imidazol-2-ylidene, imidazolidin-2-ylidene, tetrahydropyrymid-2-ylidene, cyclopropenylidene) or carbodiphosphorane ((PH3)2C, (NH3)2C) molecule. The investigated dimers are characterized by a very strong charge transfer effect from either the carbene or carbodiphosphorane molecule to the MX2 one. This may even be over six times as strong as in the water dimer. According to the QTAIM and NCI method, the zinc bond is not very different than the beryllium bond, with both featuring a significant covalent contribution. However, the zinc bond should be definitely stronger if delocalization index is considered.
Design, Synthesis, and Antimicrobial Activity of Certain New Indole-1,2,4 Triazole Conjugates
Authors: Al-Wabli Reem I. , Alsulami Mona A. , Bukhari Sarah I. , Moubayed Nadine M. S. , Al-Mutairi Maha S. , Attia Mohamed I.
Published: April 2021

The increasing prevalence of microbial infections and the emergence of resistance to the currently available antimicrobial drugs urged the development of potent new chemical entities with eminent pharmacokinetic and/or pharmacodynamic profiles. Thus, a series of new indole-triazole conjugates 6a-u was designed and synthesized to be assessed as new antimicrobial candidates using the diameter of the inhibition zone and minimum inhibitory concentration assays against certain microbial strains. Their in vitro antibacterial evaluation revealed good to moderate activity against most of the tested Gram-negative strains with diameter of the inhibition zone (DIZ) values in the range of 11–15 mm and minimum inhibition concentration (MIC) values around 250 µg/mL. Meanwhile, their in vitro antifungal evaluation demonstrated a potent activity against Candida tropicalis with MIC value as low as 2 µg/mL for most of the tested compounds. Moreover, compound 6f is the most potent congener with an MIC value of 2 µg/mL against Candida albicans.
Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness
Authors: Rudzinska Magdalena , Czarnecka-Chrebelska Karolina H. , Kuznetsova Ekaterina B. , Maryanchik Sofya V. , Parodi Alessandro , Korolev Dmitry O. , Potoldykova Nataliya , Svetikova Yulia , Vinarov Andrey Z. , Nemtsova Marina V. , Zamyatnin Andrey A.
Published: April 2021

Long non-coding RNAs (lncRNAs) can be specifically expressed in different tissues and cancers. By controlling the gene expression at the transcriptional and translational levels, lncRNAs have been reported to be involved in tumor growth and metastasis. Recent data demonstrated that multiple lncRNAs have a crucial role in renal cell carcinoma (RCC) progression—the most common malignant urogenital tumor. In the present study, we found a trend towards increased PROX1 antisense RNA 1 (PROX1-AS1) expression in RCC specimens compared to non-tumoral margins. Next, we found a positive correlation between PROX1-AS1 expression and the occurrence of distant and lymph node metastasis, higher tumor stage (pT1 vs. pT2 vs. pT3–T4) and high-grade (G1/G2 vs. G3/G4) clear RCC. Furthermore, global demethylation in RCC-derived cell lines (769-P and A498) and human embryonic kidney 293 (HEK293) cells induced a significant increase of PROX1-AS1 expression level, with the most remarkable change in HEK293 cells. In line with this evidence, bisulfite sequencing analysis confirmed the specific demethylation of bioinformatically selected CpG islands on the PROX1-AS1 promoter sequence in the HEK293 cell line but not in the tumor cells. Additionally, the human specimen analysis showed the hemimethylated state of CG dinucleotides in non-tumor kidney tissues, whereas the tumor samples presented the complete, partial, or no demethylation of CpG-islands. In conclusion, our study indicated that PROX1-AS1 could be associated with RCC progression, and further investigations may define its role as a new diagnostic marker and therapeutic target.
Association of Gut Microbiome and Vitamin D Deficiency in Knee Osteoarthritis Patients: A Pilot Study
Authors: Ramasamy Boopalan , Magne Fabien , Tripathy Sujit Kumar , Venugopal Giriprasad , Mukherjee Diptasree , Balamurugan Ramadass
Published: April 2021

Background: Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/mL). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified, and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined comorbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups was observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD, while Parabacteroides, Butyricimonas and Gordonibacter were abundant in the KOA_VDD group, and Peptococcus, Intestimonas, Delftia and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labelled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D and knee osteoarthritis.
Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial
Authors: Neumer Franka , Urraca Orenci , Alonso Joaquin , Palencia Jesús , Varea Vicente , Theis Stephan , Rodriguez-Palmero Maria , Moreno-Muñoz José Antonio , Guarner Francisco , Veereman Gigi , Vandenplas Yvan , Campoy Cristina
Published: April 2021

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.
Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial
Authors: Mieszkowski Jan , Borkowska Andżelika , Stankiewicz Błażej , Kochanowicz Andrzej , Niespodziński Bartłomiej , Surmiak Marcin , Waldziński Tomasz , Rola Rafał , Petr Miroslav , Antosiewicz Jędrzej
Published: April 2021

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.
In Silico Prediction of Drug–Drug Interactions Mediated by Cytochrome P450 Isoforms
Authors: Dmitriev Alexander V. , Rudik Anastassia V. , Karasev Dmitry A. , Pogodin Pavel V. , Lagunin Alexey A. , Filimonov Dmitry A. , Poroikov Vladimir V.
Published: April 2021

Drug–drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and include an assessment of the DDIs potential mediated by inhibition or induction of the most important drug-metabolizing cytochrome P450 isoforms. Our study was dedicated to creating a computer model for prediction of the DDIs mediated by the seven most important P450 cytochromes: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. For the creation of structure–activity relationship (SAR) models that predict metabolism-mediated DDIs for pairs of molecules, we applied the Prediction of Activity Spectra for Substances (PASS) software and Pairs of Substances Multilevel Neighborhoods of Atoms (PoSMNA) descriptors calculated based on structural formulas. About 2500 records on DDIs mediated by these cytochromes were used as a training set. Prediction can be carried out both for known drugs and for new, not-yet-synthesized substances. The average accuracy of the prediction of DDIs mediated by various isoforms of cytochrome P450 estimated by leave-one-out cross-validation (LOO CV) procedures was about 0.92. The SAR models created are publicly available as a web resource and provide predictions of DDIs mediated by the most important cytochromes P450.
Supercritical Fluid Technology for the Development of 3D Printed Controlled Drug Release Dosage Forms
Authors: Schmid Johannes , Wahl Martin A. , Daniels Rolf
Published: April 2021

Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from polylactic acid (PLA) using a fused deposition modelling (FDM) 3D printer. The 3D printed drug carriers were then loaded with Ibuprofen as a model drug, employing the controlled particle deposition (CPD) process from supercritical CO2. Carriers with varying pore sizes (0.027–0.125 mm) were constructed and loaded with Ibuprofen to yield drug-loaded carriers with a total amount of 0.83–2.67 mg API (0.32–1.41% w/w). Dissolution studies of the carriers show a significantly decreasing dissolution rate with decreasing pore sizes with a mean dissolution time (MDT) of 8.7 min for the largest pore size and 128.2 min for the smallest pore size. The API dissolution mechanism from the carriers was determined to be Fickian diffusion from the non-soluble, non-swelling carriers. Using 3D printing in combination with the CPD process, we were able to develop dosage forms with individually tailored controlled drug release. The dissolution rate of our dosage forms can be easily adjusted to the individual needs by modifying the pore sizes of the 3D printed carriers.
Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material
Authors: Tanaka Hiroki , Takata Nae , Sakurai Yu , Yoshida Tokuyuki , Inoue Takao , Tamagawa Shinya , Nakai Yuta , Tange Kota , Yoshioka Hiroki , Maeki Masatoshi , Tokeshi Manabu , Akita Hidetaka
Published: April 2021

The world-first success of lipid nanoparticle (LNP)-based siRNA therapeutics (ONPATTRO®) promises to accelerate developments in siRNA therapeutics/gene therapy using LNP-type drug delivery systems (DDS). In this study, we explore the optimal composition of an LNP containing a self-degradable material (ssPalmO-Phe) for the delivery of oligonucleotides. siRNA or antisense oligonucleotides (ASO) were encapsulated in LNP with different lipid compositions. The hepatic knockdown efficiency of the target genes and liver toxicity were evaluated. The optimal compositions for the siRNA were different from those for ASO, and different from those for mRNA that were reported in a previous study. Extracellular stability, endosomal escape and cellular uptake appear to be the key processes for the successful delivery of mRNA, siRNA and ASO, respectively. Moreover, the compositions of the LNPs likely contribute to their toxicity. The lipid composition of the LNP needs to be optimized depending on the type of nucleic acids under consideration if the applications of LNPs are to be further expanded.
Techniques for Background Identification in the Search for Rare Processes with Crystal Scintillators
Authors: Cappella Fabio , Incicchitti Antonella
Published: April 2021

In astroparticle, nuclear and subnuclear physics, low-counting experiments play an increasingly important role in the investigation of rare processes such as dark matter, double beta decay, some neutrino processes and low-background spectrometry. Extremely low-background features are more and more required to produce detectors and apparata of suitable sensitivity. Over time, a great deal of interest and attention in developing experimental techniques suitable to improve, verify and maintain the radiopurity of these detectors has arisen. In this paper, the characterization of inorganic crystal scintillators (such as, e.g., NaI(Tl), ZnWO4 and CdWO4) using α, β and γ radioactive sources and the main experimental techniques applied in the field to quantitatively identify the radioactive contaminants are highlighted; in particular, we focus on inorganic crystal scintillators, widely used in rare processes investigation, considering their applications at noncryogenic temperatures in the framework of the DAMA experiment activities at the Gran Sasso National Laboratory of the INFN (National Institute for Nuclear Physics, INFN).