bluuebunny/crossref_metadata_2025 huggingface dataset:
Dielectrophoresis-Based Positioning of Carbon Nanotubes for Wafer-Scale Fabrication of Carbon Nanotube Devices
Authors: Kimbrough Joevonte , Williams Lauren , Yuan Qunying , Xiao Zhigang
Published: December 2020

In this paper, we report the wafer-scale fabrication of carbon nanotube field-effect transistors (CNTFETs) with the dielectrophoresis (DEP) method. Semiconducting carbon nanotubes (CNTs) were positioned as the active channel material in the fabrication of carbon nanotube field-effect transistors (CNTFETs) with dielectrophoresis (DEP). The drain-source current (IDS) was measured as a function of the drain-source voltage (VDS) and gate-source voltage (VGS) from each CNTFET on the fabricated wafer. The IDS on/off ratio was derived for each CNTFET. It was found that 87% of the fabricated CNTFETs was functional, and that among the functional CNTFETs, 30% of the CNTFETs had an IDS on/off ratio larger than 20 while 70% of the CNTFETs had an IDS on/off ratio lower than 20. The highest IDS on/off ratio was about 490. The DEP-based positioning of carbon nanotubes is simple and effective, and the DEP-based device fabrication steps are compatible with Si technology processes and could lead to the wafer-scale fabrication of CNT electronic devices.
Removal of Pharmaceutical Micropollutants with Integrated Biochar and Marine Microalgae
Authors: Mojiri Amin , Baharlooeian Maedeh , Kazeroon Reza Andasht , Farraji Hossein , Lou Ziyang
Published: December 2020

Using microalgae to remove pharmaceuticals and personal care products (PPCPs) micropollutants (MPs) have attracted considerable interest. However, high concentrations of persistent PPCPs can reduce the performance of microalgae in remediating PPCPs. Three persistent PPCPs, namely, carbamazepine (CBZ), sulfamethazine (SMT) and tramadol (TRA), were treated with a combination of Chaetoceros muelleri and biochar in a photobioreactor during this study. Two reactors were run. The first reactor comprised Chaetoceros muelleri, as the control, and the second reactor comprised Chaetoceros muelleri and biochar. The second reactor showed a better performance in removing PPCPs. Through the response surface methodology, 68.9% (0.330 mg L−1) of CBZ, 64.8% (0.311 mg L−1) of SMT and 69.3% (0.332 mg L−1) of TRA were removed at the initial concentrations of MPs (0.48 mg L−1) and contact time of 8.1 days. An artificial neural network was used in optimising elimination efficiency for each MP. The rational mean squared errors and high R2 values showed that the removal of PPCPs was optimised. Moreover, the effects of PPCPs concentration (0–100 mg L−1) on Chaetoceros muelleri were studied. Low PPCP concentrations (<40 mg L−1) increased the amounts of chlorophyll and proteins in the microalgae. However, cell viability, chlorophyll and protein contents dramatically decreased with increasing PPCPs concentrations (>40 mg L−1).
Effects of Thermal Stress on the Gut Microbiome of Juvenile Milkfish (Chanos chanos)
Authors: Hassenrück Christiane , Reinwald Hannes , Kunzmann Andreas , Tiedemann Inken , Gärdes Astrid
Published: December 2020

Milkfish, an important aquaculture species in Asian countries, are traditionally cultured in outdoor-based systems. There, they experience potentially stressful fluctuations in environmental conditions, such as temperature, eliciting changes in fish physiology. While the importance of the gut microbiome for the welfare and performance of fish has been recognized, little is known about the effects of thermal stress on the gut microbiome of milkfish and its interactions with the host’s metabolism. We investigated the gut microbiome of juvenile milkfish in a thermal stress experiment, comparing control (26 °C) and elevated temperature (33 °C) treatments over three weeks, analyzing physiological biomarkers, gut microbiome composition, and tank water microbial communities using 16S amplicon sequencing. The gut microbiome was distinct from the tank water and dominated by Cetobacterium, Enterovibrio, and Vibrio. We observed a parallel succession in both temperature treatments, with microbial communities at 33 °C differing more strongly from the control after the initial temperature increase and becoming more similar towards the end of the experiment. As proxy for the fish’s energy status, HSI (hepatosomatic index) was correlated with gut microbiome composition. Our study showed that thermal stress induced changes in the milkfish gut microbiome, which may contribute to the host’s habituation to elevated temperatures over time.
Diversity and Colonization Strategies of Endolithic Cyanobacteria in the Cold Mountain Desert of Pamir
Authors: Khomutovska Nataliia , de los Ríos Asunción , Jasser Iwona
Published: December 2020

Microorganisms can survive in extreme environments and oligotrophic habitats thanks to their specific adaptive capacity. Due to its severe and contrasting climate conditions, the cold mountain desert in Eastern Pamir provides a unique environment for analyzing microbial adaptation mechanisms occurring within colonization of endolithic habitats. This study aims to investigate the composition and structure of endolithic microbial communities and analyze the interactions between microorganisms and colonized lithic substrates. Endolithic biofilms were examined using scanning electron microscopy in backscattered electron mode (SEM-BSE) and next-generation sequencing (NGS) applying amplicon sequence variants (ASVs) approach. The investigation of the V3–V4 region of 16S rRNA gene revealed that endolithic communities are dominated by Actinobacteria (26%), Proteobacteria (23%), and Cyanobacteria (11.4%). Cyanobacteria were represented by Oxyphotobacteria with a predominance of subclasses of Oscillatoriophycidae, Synechococcophycideae, and Nostocophycidae as well as the rarely occurring Sericytochromatia. The positive correlation between the contribution of the orders Synechococcales and Rhizobiales to community structure suggests that some functionally closed taxa of Cyanobacteria and Proteobacteria can complement each other, for example, in nitrogen fixation in endolithic communities. The endolithic communities occurring in Eastern Pamir were identified as complex systems whose composition and structure seem to be influenced by the architecture of microhabitats and related microenvironmental conditions.
Phylogenetic Relationships within the Nematode Subfamily Phascolostrongylinae (Nematoda: Strongyloidea) from Australian Macropodid and Vombatid Marsupials
Authors: Sukee Tanapan , Beveridge Ian , Sabir Ahmad Jawad , Jabbar Abdul
Published: December 2020

The strongyloid nematode subfamily Phascolostrongylinae comprises parasites of the large intestine and stomach of Australian macropods and wombats. In this study, we tested the phylogenetic relationships among the genera of the Phascolostrongylinae using the first and second internal transcribed spacers of the nuclear ribosomal DNA. Monophyly was encountered in the tribe Phascolostrongylinea comprising two genera, Phascolostrongylus and Oesophagostomoides, found exclusively in the large intestine of wombats. The tribe Hypodontinea, represented by the genera Hypodontus and Macropicola from the ileum and large intestine of macropods, was also found to be monophyletic. The tribe Macropostrongyloidinea, comprising the genera Macropostrongyloides and Paramacropostrongylus, was paraphyletic with the species occurring in the stomach grouping separately from those found in the large intestines of their hosts. However, Macropostrongyloidesdissimilis from the stomach of the swamp wallaby and Paramacropostrongylus toraliformis from the large intestine of the eastern grey kangaroo were distinct from their respective congeners. This study provided strong support for the generic composition of the tribe Phascolostrongylinea. The unexpected finding of M. dissimilis and P. toraliformis being distantly related to their respective congeners suggests a requirement for future taxonomic revision that may warrant separation of these species at the generic level.
Escherichia coli HS and Enterotoxigenic Escherichia coli Hinder Stress Granule Assembly
Authors: Velásquez Felipe , Marín-Rojas Josefina , Soto-Rifo Ricardo , Torres Alexia , Del Canto Felipe , Valiente-Echeverría Fernando
Published: December 2020

Escherichia coli, one of the most abundant bacterial species in the human gut microbiota, has developed a mutualistic relationship with its host, regulating immunological responses. In contrast, enterotoxigenic E. coli (ETEC), one of the main etiologic agents of diarrheal morbidity and mortality in children under the age of five in developing countries, has developed mechanisms to reduce the immune-activator effect to carry out a successful infection. Following infection, the host cell initiates the shutting-off of protein synthesis and stress granule (SG) assembly. This is mostly mediated by the phosphorylation of translation initiator factor 2α (eIF2α). We therefore evaluated the ability of a non-pathogenic E. coli strain (E. coli HS) and an ETEC strain (ETEC 1766a) to induce stress granule assembly, even in response to exogenous stresses. In this work, we found that infection with E. coli HS or ETEC 1766a prevents SG assembly in Caco-2 cells treated with sodium arsenite (Ars) after infection. We also show that this effect occurs through an eIF2α phosphorylation (eIF2α-P)-dependent mechanism. Understanding how bacteria counters host stress responses will lay the groundwork for new therapeutic strategies to bolster host cell immune defenses against these pathogens.
Targeted Next-Generation Sequencing and Informatics as an Effective Tool to Establish the Composition of Bovine Piroplasm Populations in Endemic Regions
Authors: Ghafar Abdul , Koehler Anson V. , Hall Ross S. , Gauci Charles G. , Gasser Robin B. , Jabbar Abdul
Published: December 2020

Protists of the genera Babesia and Theileria (piroplasms) cause some of the most prevalent and debilitating diseases for bovines worldwide. In this study, we established and used a next-generation sequencing-informatic approach to explore the composition of Babesia and Theileria populations in cattle and water buffalo in a country (Pakistan) endemic for these pathogens. We collected individual blood samples from cattle (n = 212) and water buffalo (n = 154), extracted genomic DNAs, PCR-amplified the V4 hypervariable region of 18S small subunit rRNA gene from piroplasms, sequenced amplicons using Illumina technology, and then analysed data using bioinformatic platforms. The results revealed piroplasms in 68.9% (252/366) samples, with overall occurrence being markedly higher in cattle (85.8%) than in water buffaloes (45.5%). Babesia (B.) occultans and Theileria (T.) lestoquardi-like species were recorded for the first time in Pakistan, and, overall, T. annulata was most commonly detected (65.8%) followed by B. bovis (7.1%), B. bigemina (4.4%), and T. orientalis (0.5%), with the genetic variability within B. bovis being pronounced. The occurrence and composition of piroplasm species varied markedly across different agro-ecological zones. The high detection of T. annulata in asymptomatic animals suggested a relatively high level of endemic stability of tropical theileriosis in the bovine population.
Tennantite–Tetrahedrite-Series Minerals and Related Pyrite in the Nibao Carlin-Type Gold Deposit, Guizhou, SW China
Authors: Wei Dongtian , Xia Yong , Steadman Jeffrey A. , Xie Zhuojun , Liu Xijun , Tan Qinping , Bai Ling’an
Published: December 2020

A number of sediment-hosted, Carlin-type/-like gold deposits are distributed in the Youjiang basin of SW China. The gold ores are characterized by high As, Hg, and Sb contents but with low base metal contents (Cu+Pb+Zn < 500–1000 ppm). The Nibao deposit is unique among these gold deposits by having tennantite–tetrahedrite-series minerals in its ores. The deposit is also unique in being primarily hosted in the relatively unreactive siliceous pyroclastic rocks, unlike classic Carlin-type gold deposits that are hosted in carbonates or calcareous clastic rocks. In this study, we have identified tennantite-(Zn), tennantite-(Hg), and tetrahedrite-(Zn) from the tennantite–tetrahedrite-series mineral assemblage. The tennantite-(Zn) can be further divided into two sub-types of Tn-(Zn)-I; and Tn-(Zn)-II;. Tn-(Zn)-I; usually occurs in the core of a Tennantite–tetrahedrite composite and appears the darkest under the SEM image, whereas Tn-(Zn)-II overgrows on Tn-(Zn)-I and is overgrown by tetrahedrite-(Zn). Tennantite-(Hg) occasionally occurs as inclusions near the uneven boundary between Tn-(Zn)-I and Tn-(Zn)-II. An appreciable amount of Au (up to 3540 ppm) resides in the tennantite–tetrahedrite-series minerals, indicating that the latter is a major Au host at Nibao. The coexistence of tennantite–tetrahedrite-series minerals and Au-bearing pyrite indicates the Nibao ore fluids were more oxidized than the Carlin-type ore fluids. The tennantite–tetrahedrite series at Nibao evolved from Tn-(Zn)-I through Tn-(Zn)-II to tetrahedrite-(Zn), which is likely caused by Sb accumulation in the ore fluids. This indicates that the Nibao ore fluids may have become more reduced and less acidic during Au precipitation.
Chitosan with Bentonite and Biochar in Ni-Affected Soil Reduces Grain Ni Concentrations, Improves Soil Enzymes and Grain Quality in Lentil
Authors: Tanzeem-ul-Haq Hafiz Syed , Rasool Bilal , Ehtisham-ul-Haque Syed , Saif Sadia , Zafar Sadia , Younis Tahira , Akhtar Imran , Jafri Laila , Iqbal Naeem , Masood Nasir , Lewińska Karolina , Iqbal Muhammad
Published: December 2020

Ecological and human health risks associated with Ni-affected soils are one of the major attention seeking issues nowadays. The current investigation is based on the usage of biochar (BR), chitosan (CN), bentonite (BE), and their mixture to immobilize Ni in a Ni-polluted soil and accordingly contracted Ni distribution in lentil plant parts, improved grain nutritional quality, antioxidant defense system, and soil enzymatic activities. The soil was initially amended with CN, BE, and BR and later lentil was grown in this soil in pots. Results depicted the highest significance of BE+CN treatment in terms of reducing the Ni distribution in the roots, shoots, grain, and DTPA-extractable fractions, relative to control treatment. Contrarily, the BR+CN treatment displayed the minimum oxidative stress and the utmost plant growth, chlorophyll contents in the leaves, relative water content (RWC), micronutrient concentrations, and grain biochemistry. The BR+CN indicated the highest activities of soil enzymes. Based on the results, we recommend BE+CN treatment to reduce the Ni distribution in the lentil plant. Although, improvement in plant growth, grain quality, soil enzymes, and a significant reduction in plant oxidative stress can only be gained with BR+CN.
Identification of Dipeptidyl Peptidase-4 and α-Amylase Inhibitors from Melicope glabra (Blume) T. G. Hartley (Rutaceae) Using Liquid Chromatography Tandem Mass Spectrometry, In Vitro and In Silico Methods
Authors: Quek Alexandra , Kassim Nur Kartinee , Ismail Amin , Latif Muhammad Alif Mohammad , Shaari Khozirah , Tan Dai Chuan , Lim Pei Cee
Published: December 2020

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC50 of 169.40 μg/mL and 303.64 μg/mL, respectively. Bioassay-guided fractionation of the leaves’ chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC50: 128.35 μg/mL; α-Amylase IC50: 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4′,5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4′-dimethyl ether (7), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (−8.6 kcal/mol) was better than acarbose (−6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.
Predictive Modeling of Critical Temperatures in Superconducting Materials
Authors: Sizochenko Natalia , Hofmann Markus
Published: December 2020

In this study, we have investigated quantitative relationships between critical temperatures of superconductive inorganic materials and the basic physicochemical attributes of these materials (also called quantitative structure-property relationships). We demonstrated that one of the most recent studies (titled "A data-driven statistical model for predicting the critical temperature of a superconductor” and published in Computational Materials Science by K. Hamidieh in 2018) reports on models that were based on the dataset that contains 27% of duplicate entries. We aimed to deliver stable models for a properly cleaned dataset using the same modeling techniques (multiple linear regression, MLR, and gradient boosting decision trees, XGBoost). The predictive ability of our best XGBoost model (R2 = 0.924, RMSE = 9.336 using 10-fold cross-validation) is comparable to the XGBoost model by the author of the initial dataset (R2 = 0.920 and RMSE = 9.5 K in ten-fold cross-validation). At the same time, our best model is based on less sophisticated parameters, which allows one to make more accurate interpretations while maintaining a generalizable model. In particular, we found that the highest relative influence is attributed to variables that represent the thermal conductivity of materials. In addition to MLR and XGBoost, we explored the potential of other machine learning techniques (NN, neural networks and RF, random forests).
Crystalline Peroxosolvates: Nature of the Coformer, Hydrogen-Bonded Networks and Clusters, Intermolecular Interactions
Authors: Medvedev Alexander G. , Churakov Andrei V. , Prikhodchenko Petr V. , Lev Ovadia , Vener Mikhail V.
Published: December 2020

Despite the technological importance of urea perhydrate (percarbamide) and sodium percarbonate, and the growing technological attention to solid forms of peroxide, fewer than 45 peroxosolvates were known by 2000. However, recent advances in X-ray diffractometers more than tripled the number of structurally characterized peroxosolvates over the last 20 years, and even more so, allowed energetic interpretation and gleaning deeper insight into peroxosolvate stability. To date, 134 crystalline peroxosolvates have been structurally resolved providing sufficient insight to justify a first review article on the subject. In the first chapter of the review, a comprehensive analysis of the structural databases is carried out revealing the nature of the co-former in crystalline peroxosolvates. In the majority of cases, the coformers can be classified into three groups: (1) salts of inorganic and carboxylic acids; (2) amino acids, peptides, and related zwitterions; and (3) molecular compounds with a lone electron pair on nitrogen and/or oxygen atoms. The second chapter of the review is devoted to H-bonding in peroxosolvates. The database search and energy statistics revealed the importance of intermolecular hydrogen bonds (H-bonds) which play a structure-directing role in the considered crystals. H2O2 always forms two H-bonds as a proton donor, the energy of which is higher than the energy of analogous H-bonds existing in isostructural crystalline hydrates. This phenomenon is due to the higher acidity of H2O2 compared to water and the conformational mobility of H2O2. The dihedral angle H-O-O-H varies from 20 to 180° in crystalline peroxosolvates. As a result, infinite H-bonded 1D chain clusters are formed, consisting of H2O2 molecules, H2O2 and water molecules, and H2O2 and halogen anions. H2O2 can form up to four H-bonds as a proton acceptor. The third chapter of the review is devoted to energetic computations and in particular density functional theory with periodic boundary conditions. The approaches are considered in detail, allowing one to obtain the H-bond energies in crystals. DFT computations provide deeper insight into the stability of peroxosolvates and explain why percarbamide and sodium percarbonate are stable to H2O2/H2O isomorphic transformations. The review ends with a description of the main modern trends in the synthesis of crystalline peroxosolvates, in particular, the production of peroxosolvates of high-energy compounds and mixed pharmaceutical forms with antiseptic and analgesic effects.
Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis
Authors: Weinberg Samuel E. , Sun Le Yu , Yang Allison L. , Liao Jie , Yang Guang Yu
Published: December 2020

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.
Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer Conjugates
Authors: Soe Tet Htut , Watanabe Kazunori , Ohtsuki Takashi
Published: December 2020

Endosomal escape in cell-penetrating peptide (CPP)-based drug/macromolecule delivery systems is frequently insufficient. The CPP-fused molecules tend to remain trapped inside endosomes and end up being degraded rather than delivered into the cytosol. One of the methods for endosomal escape of CPP-fused molecules is photochemical internalization (PCI), which is based on the use of light and a photosensitizer and relies on photoinduced endosomal membrane destabilization to release the cargo molecule. Currently, it remains unclear how this delivery strategy behaves after photostimulation. Recent findings, including our studies using CPP-cargo-photosensitizer conjugates, have shed light on the photoinduced endosomal escape mechanism. In this review, we discuss the structural design of CPP-photosensitizer and CPP-cargo-photosensitizer conjugates, and the PCI mechanism underlying their application.
Importance of the C12 Carbon Chain in the Biological Activity of Rhamnolipids Conferring Protection in Wheat against Zymoseptoria tritici
Authors: Platel Rémi , Chaveriat Ludovic , Le Guenic Sarah , Pipeleers Rutger , Magnin-Robert Maryline , Randoux Béatrice , Trapet Pauline , Lequart Vincent , Joly Nicolas , Halama Patrice , Martin Patrick , Höfte Monica , Reignault Philippe , Siah Ali
Published: December 2020

The hemibiotrophic fungus Zymoseptoria tritici, responsible for Septoria tritici blotch, is currently the most devastating foliar disease on wheat crops worldwide. Here, we explored, for the first time, the ability of rhamnolipids (RLs) to control this pathogen, using a total of 19 RLs, including a natural RL mixture produced by Pseudomonas aeruginosa and 18 bioinspired RLs synthesized using green chemistry, as well as two related compounds (lauric acid and dodecanol). These compounds were assessed for in vitro antifungal effect, in planta defence elicitation (peroxidase and catalase enzyme activities), and protection efficacy on the wheat-Z. tritici pathosystem. Interestingly, a structure-activity relationship analysis revealed that synthetic RLs with a 12 carbon fatty acid tail were the most effective for all examined biological activities. This highlights the importance of the C12 chain in the bioactivity of RLs, likely by acting on the plasma membranes of both wheat and Z. tritici cells. The efficacy of the most active compound Rh-Est-C12 was 20-fold lower in planta than in vitro; an optimization of the formulation is thus required to increase its effectiveness. No Z. tritici strain-dependent activity was scored for Rh-Est-C12 that exhibited similar antifungal activity levels towards strains differing in their resistance patterns to demethylation inhibitor fungicides, including multi-drug resistance strains. This study reports new insights into the use of bio-inspired RLs to control Z. tritici.
Two New Aristolochic Acid Analogues from the Roots of Aristolochia contorta with Significant Cytotoxic Activity
Authors: Ji Hong-Jian , Li Jia-Yuan , Wu Shi-Fei , Wu Wen-Yong , Yao Chang-Liang , Yao Shuai , Zhang Jian-Qing , Guo De-An
Published: December 2020

Twelve compounds, including two new aristolochic acid analogues with a formyloxy moiety (9–10) and 10 known aristolochic acid derivates (1–8 and 11–12), were obtained from the roots of Aristolochiacontorta. Their structures were elucidated using extensive spectroscopic methods. Their cytotoxic activity in human proximal tubular cells HK-2 was evaluated by the MTT method, which has been widely used to assess cell viability. Among these molecules, compounds 3 and 9 were found to be more cytotoxic. Furthermore, molecular modeling was used to evaluate, for the first time, the interactions of compounds 3 and 9 with the target protein organic anionic transporter 1 (OAT1) that plays a key role in mediating aristolochic acid nephropathy. Structure–activity relationships are briefly discussed.
Modeling and Epitaxial Growth of Homogeneous Long-InGaN Nanowire Structures
Authors: Kim Sung-Un , Ra Yong-Ho
Published: December 2020

One-dimensional nanowires based on Group III-nitride materials are emerging as one of the most promising structures for applications of light-emitting diodes (LEDs), laser diodes (LDs), solar cells, and photocatalysts. However, leading to the so-called “green gap” in photonics, the fabrication of high concentration indium gallium nitride (InGaN) and long-InGaN structures remains still challenging. In this study, we performed simulations for structural modeling of uniform temperature distribution in a nanowire epitaxy, and have successfully developed high-concentration InGaN and long-InGaN nanowire heterostructures on silicon (Si) substrate using molecular beam epitaxy (MBE) system. From scanning electron microscope (SEM) and transmission electron microscope (TEM) results, it was confirmed that the various doped-InGaN nanowire structures show much higher crystal quality compared to conventional nanowire structures. By introducing a new three-step modulated growth technique, the n-/p-InGaN active regions were greatly increased and the optical properties were also dramatically improved due to reduced phase separation. In addition, a multi-band p-InGaN/GaN heterostructure was successfully fabricated with the core–shell nanowire structures, which enable the emission of light in the entire visible spectral range, and protect the InGaN surface from surface recombination. This paper offers important insight into the design and epitaxial growth of InGaN nanowire heterostructures.
Road Map to Understanding SARS-CoV-2 Clinico-Immunopathology and COVID-19 Disease Severity
Authors: Karmakar Deepmala , Lahiri Basudev , Ranjan Piyush , Chatterjee Jyotirmoy , Lahiri Pooja , Sengupta Sanghamitra
Published: December 2020

SARS-CoV-2, a novel coronavirus, was first identified in Wuhan, China in December 2019. The rapid spread of the virus worldwide prompted the World Health Organization (WHO) to declare COVID-19 a pandemic in March 2020. COVID-19 discontinuing’s a global health crisis. Approximately 80% of the patients infected with SARS-CoV-2 display undetectable to mild inflammation confined in the upper respiratory tract. In remaining patients, the disease turns into a severe form affecting almost all major organs predominantly due to an imbalance of innate and adaptive arms of host immunity. The purpose of the present review is to narrate the virus’s invasion through the system and the host’s reaction. A thorough discussion on disease severity is also presented regarding the behavior of the host’s immune system, which gives rise to the cytokine storm particularly in elderly patients and those with comorbidities. A multifaceted yet concise description of molecular aspects of disease progression and its repercussion on biochemical and immunological features in infected patients is tabulated. The summary of pathological, clinical, immunological, and molecular accounts discussed in this review is of theranostic importance to clinicians for early diagnosis of COVID-19 and its management.
Poxviral Strategies to Overcome Host Cell Apoptosis
Authors: Suraweera Chathura D. , Hinds Mark G. , Kvansakul Marc
Published: December 2020

Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections.
Preclinical Evaluation of Oral Urolithin-A for the Treatment of Acute Campylobacteriosis in Campylobacter jejuni Infected Microbiota-Depleted IL-10−/− Mice
Authors: Mousavi Soraya , Weschka Dennis , Bereswill Stefan , Heimesaat Markus M.
Published: December 2020

Human campylobacteriosis represents an infectious enteritis syndrome caused by Campylobacter species, mostly Campylobacter jejuni. Given that C. jejuni infections are rising worldwide and antibiotic treatment is usually not indicated, novel treatment options for campylobacteriosis are needed. Urolithin-A constitutes a metabolite produced by the human gut microbiota from ellagitannins and ellagic acids in berries and nuts which have been known for their health-beneficial including anti-inflammatory effects since centuries. Therefore, we investigated potential pathogen-lowering and immunomodulatory effects following oral application of synthetic urolithin-A during acute campylobacteriosis applying perorally C. jejuni infected, microbiota-depleted IL-10−/− mice as preclinical inflammation model. On day 6 post infection, urolithin-A treated mice harbored slightly lower pathogen loads in their ileum, but not colon as compared to placebo counterparts. Importantly, urolithin-A treatment resulted in an improved clinical outcome and less pronounced macroscopic and microscopic inflammatory sequelae of infection that were paralleled by less pronounced intestinal pro-inflammatory immune responses which could even be observed systemically. In conclusion, this preclinical murine intervention study provides first evidence that oral urolithin-A application is a promising treatment option for acute C. jejuni infection and paves the way for future clinical studies in human campylobacteriosis.
Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation
Authors: Pandey Manisha , Choudhury Hira , Abdul-Aziz Azila , Bhattamisra Subrat Kumar , Gorain Bapi , Su Jocelyn Sziou Ting , Tan Choo Leey , Chin Woon Yee , Yip Khar Yee
Published: December 2020

The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs’ poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended.
Effect of Diphenyleneiodonium Chloride on Intracellular Reactive Oxygen Species Metabolism with Emphasis on NADPH Oxidase and Mitochondria in Two Therapeutically Relevant Human Cell Types
Authors: Zavadskis Sergejs , Weidinger Adelheid , Hanetseder Dominik , Banerjee Asmita , Schneider Cornelia , Wolbank Susanne , Marolt Presen Darja , Kozlov Andrey V.
Published: December 2020

Reactive oxygen species (ROS) have recently been recognized as important signal transducers, particularly regulating proliferation and differentiation of cells. Diphenyleneiodonium (DPI) is known as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) and is also affecting mitochondrial function. The aim of this study was to investigate the effect of DPI on ROS metabolism and mitochondrial function in human amniotic membrane mesenchymal stromal cells (hAMSCs), human bone marrow mesenchymal stromal cells (hBMSCs), hBMSCs induced into osteoblast-like cells, and osteosarcoma cell line MG-63. Our data suggested a combination of a membrane potential sensitive fluorescent dye, tetramethylrhodamine methyl ester (TMRM), and a ROS-sensitive dye, CM-H2DCFDA, combined with a pretreatment with mitochondria-targeted ROS scavenger MitoTEMPO as a good tool to examine effects of DPI. We observed critical differences in ROS metabolism between hAMSCs, hBMSCs, osteoblast-like cells, and MG-63 cells, which were linked to energy metabolism. In cell types using predominantly glycolysis as the energy source, such as hAMSCs, DPI predominantly interacted with NOX, and it was not toxic for the cells. In hBMSCs, the ROS turnover was influenced by NOX activity rather than by the mitochondria. In cells with aerobic metabolism, such as MG 63, the mitochondria became an additional target for DPI, and these cells were prone to the toxic effects of DPI. In summary, our data suggest that undifferentiated cells rather than differentiated parenchymal cells should be considered as potential targets for DPI.
Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice
Authors: Michael Johanna , Bessa de Sousa Diana , Conway Justin , Gonzalez-Labrada Erick , Obeid Rodolphe , Tevini Julia , Felder Thomas , Hutter-Paier Birgit , Zerbe Horst , Paiement Nadine , Aigner Ludwig
Published: December 2020

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.
3D Printed Microfluidic Devices for Drug Release Assays
Authors: Amoyav Benzion , Goldstein Yoel , Steinberg Eliana , Benny Ofra
Published: December 2020

Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on a 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional “batch” or microfluidic method, based on an optimized solid-in-oil-in-water protocol. Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the “V” shape barrier was similar to that of the dialysis sac test and differed from the “basket” barrier design. Importantly, a cytotoxicity test confirmed biocompatibility of the printed resin. Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication.
Biodegradable Microcapsules Loaded with Nerve Growth Factor Enable Neurite Guidance and Synapse Formation
Authors: Kopach Olga , Pavlov Anton M. , Sindeeva Olga A. , Sukhorukov Gleb B. , Rusakov Dmitri A.
Published: December 2020

Neurological disorders and traumas often involve loss of specific neuronal connections, which would require intervention with high spatial precision. We have previously demonstrated the biocompatibility and therapeutic potential of the layer-by-layer (LbL)-fabricated microcapsules aimed at the localized delivery of specific channel blockers to peripheral nerves. Here, we explore the potential of LbL-microcapsules to enable site-specific, directional action of neurotrophins to stimulate neuronal morphogenesis and synaptic circuit formation. We find that nanoengineered biodegradable microcapsules loaded with nerve growth factor (NGF) can guide the morphological development of hippocampal neurons in vitro. The presence of NGF-loaded microcapsules or their clusters increases the neurite outgrowth rate while boosting neurite branching. Microcapsule clusters appear to guide the trajectory of developing individual axons leading to the formation of functional synapses. Our observations highlight the potential of NGF-loaded, biodegradable LbL-microcapsules to help guide axonal development and possibly circuit regeneration in neuropathology.
Nano-Fertilization as an Emerging Fertilization Technique: Why Can Modern Agriculture Benefit from Its Use?
Authors: Seleiman Mahmoud F. , Almutairi Khalid F. , Alotaibi Majed , Shami Ashwag , Alhammad Bushra Ahmed , Battaglia Martin Leonardo
Published: December 2020

There is a need for a more innovative fertilizer approach that can increase the productivity of agricultural systems and be more environmentally friendly than synthetic fertilizers. In this article, we reviewed the recent development and potential benefits derived from the use of nanofertilizers (NFs) in modern agriculture. NFs have the potential to promote sustainable agriculture and increase overall crop productivity, mainly by increasing the nutrient use efficiency (NUE) of field and greenhouse crops. NFs can release their nutrients at a slow and steady pace, either when applied alone or in combination with synthetic or organic fertilizers. They can release their nutrients in 40–50 days, while synthetic fertilizers do the same in 4–10 days. Moreover, NFs can increase the tolerance of plants against biotic and abiotic stresses. Here, the advantages of NFs over synthetic fertilizers, as well as the different types of macro and micro NFs, are discussed in detail. Furthermore, the application of NFs in smart sustainable agriculture and the role of NFs in the mitigation of biotic and abiotic stress on plants is presented. Though NF applications may have many benefits for sustainable agriculture, there are some concerns related to the release of nanoparticles (NPs) from NFs into the environment, with the subsequent detrimental effects that this could have on both human and animal health. Future research should explore green synthesized and biosynthesized NFs, their safe use, bioavailability, and toxicity concerns.
Global Distribution of the Reniform Nematode Genus Rotylenchulus with the Synonymy of Rotylenchulus macrosoma with Rotylenchulus borealis
Authors: Palomares-Rius Juan E. , Clavero-Camacho Ilenia , Archidona-Yuste Antonio , Cantalapiedra-Navarrete Carolina , León-Ropero Guillermo , Braun Miyara Sigal , Karssen Gerrit , Castillo Pablo
Published: December 2020

Reniform nematodes of the genus Rotylenchulus are semi-endoparasites of numerous herbaceous and woody plant roots that occur largely in regions with temperate, subtropical, and tropical climates. In this study, we compared 12 populations of Rotylenchulusborealis and 16 populations of Rotylenchulusmacrosoma, including paratypes deposited in nematode collections, confirming that morphological characters between both nematode species do not support their separation. In addition, analysis of molecular markers using nuclear ribosomal DNA (28S, ITS1) and mitochondrial DNA (coxI) genes, as well as phylogenetic approaches, confirmed the synonymy of R. macrosoma with R. borealis. This study also demonstrated that R. borealis (= macrosoma) from Israel has two distinct rRNA gene types in the genome, specifically the two types of D2-D3 (A and B). We provide a global geographical distribution of the genus Rotylenchulus. The two major pathogenic species (Rotylenchulusreniformis and Rotylenchulusparvus) showed their close relationship with warmer areas with high annual mean temperature, maximum temperature of the warmest month, and minimum temperature of the coldest month. The present study confirms the extraordinary morphological and molecular diversity of R. borealis in Europe, Africa, and the Middle East and comprises a paradigmatic example of remarkable flexibility of ecological requirements within reniform nematodes.
Evaluation of Anionic Eco-Friendly Flocculants Prepared from Eucalyptus Pulps with Diverse Lignin Contents for Application in Effluent Treatment
Authors: Grenda Kinga , Gamelas José A. F. , Arnold Julien , Pellizzer Lorenzo , Cayre Olivier J. , Rasteiro Maria G.
Published: December 2020

Modification of cellulosic-rich materials for the production of cellulose-based polyelectrolytes (PELs) can bring several benefits, such as high biodegradability and low or no toxicity, for numerous applications, when compared with the use of traditional, synthetic PELs. Moreover, cellulose-based PELs originating from wood wastes, contribute to the valorisation of such wastes. In this work, Eucalyptus pulps with diverse lignin contents, extracted from Eucalyptus wood wastes, were anionized by a two–step reaction procedure (periodate oxidation followed by sulfonation). Applying different reaction times (24–144 h) in the sulfonation step allowed for producing a range of cellulose-based anionic PELs with different characteristics. PELs obtained after 24 and 72 h of sulfonation were thoroughly characterized (Fourier transform infrared and 1H nuclear magnetic resonance spectroscopies, anionic group content (elemental analysis), zeta potential and hydrodynamic diameter (dynamic light scattering)) and subsequently evaluated as flocculants in decolouration processes of model effluents (Methylene Blue and Crystal Violet) and an industrial effluent from a textile industry. Furthermore, possible flocculation mechanisms induced by the use of the various PELs are discussed. Results are compared with those obtained with a commonly applied, synthetic flocculant (polyacrylamide). It is demonstrated that it was possible to obtain water-soluble lignocellulosic PELs starting from raw materials with different degrees of purity and that those PELs are promising eco-friendly alternative flocculation agents for the decolouration of effluents.