bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and Numerical Analysis of Mode I Fracture Process of Rock by Semi-Circular Bend Specimen
Authors: Xiao Peng , Li Diyuan , Zhao Guoyan , Liu Meng
Published: July 2021

The semi-circular bend (SCB) specimen is widely used to measure fracture toughness of brittle materials such as rock. In this work, the stress field, fracture process zone (FPZ), and crack propagation velocity of SCB specimen are analyzed during the fracture process of rock specimens. The FPZ of specimen is obtained by experimental and numerical methods under a three-point bend test. The stress concentration zones of specimen present a heart shape at peak load points. FPZ forms before macro fracture occurs. The macro fracture form inside FPZ in a post-peak region of a load–displacement curve. The crack propagation process of specimen include two stages, namely the rapid crack initial development stage, and the final crack splitting stage. The maximum crack propagation velocity of specimen is about 267 m/s, and the average crack propagation velocity is about 111 m/s.
Decision Support System for Evaluating Suitable Job Applicants
Authors: Walek Bogdan , Pektor Ondrej , Farana Radim
Published: July 2021

This paper describes a novel approach in the area of evaluating suitable job applicants for various job positions, and specifies typical areas of requirement and their usage. Requirements for this decision-support system are defined in order to be used in middle-size companies. Suitable tools chosen were fuzzy expert systems, primarily the inference system Takagi-Sugeno type, which were then supplied with implementation of methods of variant multi-criteria analysis. The resulting system is a variable tool with the possibility to simply set the importance of individual selection criteria so that it can be used in various situations, primarily in repeated selection procedures for similar job positions. A strong emphasis is devoted to the explanatory module, which enables the results of the expert system to be used easily. Verification of the system on real data in cooperation with a collaborating company has proved that the system is easily usable.
Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice
Authors: Martínez-García Gemma G. , Pérez Raúl F. , Fernández Álvaro F. , Durand Sylvere , Kroemer Guido , Mariño Guillermo
Published: July 2021

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.
Ultrasonic Particle Manipulation in Glass Capillaries: A Concise Review
Authors: Liu Guotian , Lei Junjun , Cheng Feng , Li Kemin , Ji Xuanrong , Huang Zhigang , Guo Zhongning
Published: July 2021

Ultrasonic particle manipulation (UPM), a non-contact and label-free method that uses ultrasonic waves to manipulate micro- or nano-scale particles, has recently gained significant attention in the microfluidics community. Moreover, glass is optically transparent and has dimensional stability, distinct acoustic impedance to water and a high acoustic quality factor, making it an excellent material for constructing chambers for ultrasonic resonators. Over the past several decades, glass capillaries are increasingly designed for a variety of UPMs, e.g., patterning, focusing, trapping and transporting of micron or submicron particles. Herein, we review established and emerging glass capillary-transducer devices, describing their underlying mechanisms of operation, with special emphasis on the application of glass capillaries with fluid channels of various cross-sections (i.e., rectangular, square and circular) on UPM. We believe that this review will provide a superior guidance for the design of glass capillary-based UPM devices for acoustic tweezers-based research.
Liquid Flow and Mass Transfer Behaviors in a Butterfly-Shaped Microreactor
Authors: Lv Haicheng , Yang Zhirong , Zhang Jing , Qian Gang , Duan Xuezhi , Shu Zhongming , Zhou Xinggui
Published: July 2021

Based on the split-and-recombine principle, a millimeter-scale butterfly-shaped microreactor was designed and fabricated through femtosecond laser micromachining. The velocity fields, streamlines and pressure fields of the single-phase flow in the microreactor were obtained by a computational fluid dynamics simulation, and the influence of flow rates on the homogeneous mixing efficiency was quantified by the mixing index. The flow behaviors in the microreactor were investigated using water and n-butanol, from which schematic diagrams of various flow patterns were given and a flow pattern map was established for regulating the flow behavior via controlling the flow rates of the two-phase flow. Furthermore, effects of the two-phase flow rates on the droplet flow behavior (droplet number, droplet size and standard deviation) in the microreactor were investigated. In addition, the interfacial mass transfer behaviors of liquid–liquid flow were evaluated using the standard low interfacial tension system of “n-butanol/succinic acid/water”, where the dependence between the flow pattern and mass transfer was discussed. The empirical relationship between the volumetric mass transfer coefficient and Reynold number was established with prediction error less than 20%.
Gate-Stack Engineering to Improve the Performance of 28 nm Low-Power High-K/Metal-Gate Device
Authors: Park Jeewon , Jang Wansu , Shin Changhwan
Published: July 2021

In this study, a gate-stack engineering technique is proposed as a means of improving the performance of a 28 nm low-power (LP) high-k/metal-gate (HK/MG) device. In detail, it was experimentally verified that HfSiO thin films can replace HfSiON congeners, where the latter are known to have a good thermal budget and/or electrical characteristics, to boost the device performance under a limited thermal budget. TiN engineering for the gate-stack in the 28 nm LP HK/MG device was used to suppress the gate leakage current. Using the proposed fabrication method, the on/off current ratio (Ion/Ioff) was improved for a given target Ion, and the gate leakage current was appropriately suppressed. Comparing the process-of-record device against the 28 nm LP HK/MG device, the thickness of the electrical oxide layer in the new device was reduced by 3.1% in the case of n-type field effect transistors and by 10% for p-type field effect transistors. In addition, the reliability (e.g., bias temperature instability, hot carrier injury, and time-dependent dielectric breakdown) of the new device was evaluated, and it was observed that there was no conspicuous risk. Therefore, the HfSiO film can afford reliable performance enhancement when employed in the 28 nm LP HK/MG device with a limited thermal budget.
Molecular Phylogeny of Unicellular Marine Coccoid Green Algae Revealed New Insights into the Systematics of the Ulvophyceae (Chlorophyta)
Authors: Darienko Tatyana , Rad-Menéndez Cecilia , Campbell Christine N. , Pröschold Thomas
Published: July 2021

Most marine coccoid and sarcinoid green algal species have traditionally been placed within genera dominated by species from freshwater or soil habitats. For example, the genera Chlorocystis and Halochlorococcum contain exclusively marine species; however, their familial and ordinal affinities are unclear. They are characterized by a vegetative cell with lobated or reticulated chloroplast, formation of quadriflagellated zoospores and living epi- or endophytically within benthic macroalgae. They were integrated into the family Chlorochytriaceae which embraces all coccoid green algae with epi- or endophytic life phases. Later, they were excluded from the family of Chlorococcales based on studies of their life histories in culture, and transferred to their newly described order, Chlorocystidales of the Ulvophyceae. Both genera form a “Codiolum”-stage that serves as the unicellular sporophyte in their life cycles. Phylogenetic analyses of SSU and ITS rDNA sequences confirmed that these coccoid taxa belong to the Chlorocystidales, together with the sarcinoid genus Desmochloris. The biflagellated coccoid strains were members of the genus Sykidion, which represented its own order, Sykidiales, among the Ulvophyceae. Considering these results and the usage of the ITS-2/CBC approach revealed three species of Desmochloris, six of Chlorocystis, and three of Sykidion. Three new species and several new combinations were proposed.
Glucosidase Inhibitors Screening in Microalgae and Cyanobacteria Isolated from the Amazon and Proteomic Analysis of Inhibitor Producing Synechococcus sp. GFB01
Authors: Gradíssimo Diana Gomes , Oliveira da Silva Vivian Cássia , Xavier Luciana Pereira , do Nascimento Sidney Vasconcelos , Valadares Rafael Borges da Silva , Faustino Silvia Maria Mathes , Schneider Maria Paula Cruz , Santos Agenor Valadares
Published: July 2021

Microalgae and cyanobacteria are good sources for prospecting metabolites of biotechnological interest, including glucosidase inhibitors. These inhibitors act on enzymes related to various biochemical processes; they are involved in metabolic diseases, such as diabetes and Gaucher disease, tumors and viral infections, thus, they are interesting hubs for the development of new drugs and therapies. In this work, the screening of 63 environmental samples collected in the Brazilian Amazon found activity against β-glucosidase, of at least 60 min, in 13.85% of the tested extracts, with Synechococcus sp. GFB01 showing inhibitory activity of 90.2% for α-glucosidase and 96.9% against β-glucosidase. It was found that the nutritional limitation due to a reduction in the concentration of sodium nitrate, despite not being sufficient to cause changes in cell growth and photosynthetic apparatus, resulted in reduced production of α and β-glucosidase inhibitors and differential protein expression. The proteomic analysis of cyanobacteria isolated from the Amazon is unprecedented, with this being the first work to evaluate the protein expression of Synechococcus sp. GFB01 subjected to nutritional stress. This evaluation helps to better understand the metabolic responses of this organism, especially related to the production of inhibitors, adding knowledge to the industrial potential of these cyanobacterial compounds.
Surface Waters and Urban Brown Rats as Potential Sources of Human-Infective Cryptosporidium and Giardia in Vienna, Austria
Authors: Cervero-Aragó Silvia , Desvars-Larrive Amélie , Lindner Gerhard , Sommer Regina , Häfeli Iveta , Walochnik Julia
Published: July 2021

Cryptosporidium and Giardia are waterborne protozoa that cause intestinal infections in a wide range of warm-blooded animals. Human infections vary from asymptomatic to life-threatening in immunocompromised people, and can cause growth retardation in children. The aim of our study was to assess the prevalence and diversity of Cryptosporidium and Giardia in urban surface water and in brown rats trapped in the center of Vienna, Austria, using molecular methods, and to subsequently identify their source and potential transmission pathways. Out of 15 water samples taken from a side arm of the River Danube, Cryptosporidium and Giardia (oo)cysts were detected in 60% and 73% of them, with concentrations ranging between 0.3–4 oocysts/L and 0.6–96 cysts/L, respectively. Cryptosporidium and Giardia were identified in 13 and 16 out of 50 rats, respectively. Eimeria, a parasite of high veterinary importance, was also identified in seven rats. Parasite co-ocurrence was detected in nine rats. Rat-associated genotypes did not match those found in water, but matched Giardia previously isolated from patients with diarrhea in Austria, bringing up a potential role of rats as sources or reservoirs of zoonotic pathogenic Giardia. Following a One Health approach, molecular typing across potential animal and environmental reservoirs and human cases gives an insight into environmental transmission pathways and therefore helps design efficient surveillance strategies and relevant outbreak responses.
Monazite as an Exploration Tool for Iron Oxide-Copper-Gold Mineralisation in the Gawler Craton, South Australia
Authors: Tiddy Caroline , Zivak Diana , Hill June , Giles David , Hodgkison Jim , Neumann Mitchell , Brotodewo Adrienne
Published: July 2021

The chemistry of hydrothermal monazite from the Carrapateena and Prominent Hill iron oxide-copper-gold (IOCG) deposits in the IOCG-rich Gawler Craton, South Australia, is used here to define geochemical criteria for IOCG exploration in the Gawler Craton as follows: Monazite associated with IOCG mineralisation: La + Ce > 63 wt% (where La > 22.5 wt% and Ce > 37 wt%), Y and/or Th < 1 wt% and Nd < 12.5 wt%; Intermediate composition monazite (between background and ore-related compositions): 45 wt% < La + Ce < 63 wt%, Y and/or Th < 1 wt%. Intermediate monazite compositions preserving Nd > 12.5 wt% are considered indicative of Carrapateena-style mineralisation; Background compositions: La + Ce < 45 wt% or Y or Th > 1 wt%. Mineralisation-related monazite compositions are recognised within monazite hosted within cover sequence materials that directly overly IOCG mineralisation at Carrapateena. Similar observations have been made at Prominent Hill. Recognition of these signatures within cover sequence materials demonstrates that the geochemical signatures can survive processes of weathering, erosion, transport and redeposition into younger cover sequence materials that overlie older, mineralised basement rocks. The monazite geochemical signatures therefore have the potential to be dispersed within the cover sequence, effectively increasing the geochemical footprint of mineralisation.
Recovery of Chlorogenic Acids from Agri-Food Wastes: Updates on Green Extraction Techniques
Authors: Frosi Ilaria , Montagna Irene , Colombo Raffaella , Milanese Chiara , Papetti Adele
Published: July 2021

The agri-food sector produces a huge amount of agri-food wastes and by-products, with a consequent great impact on environmental, economic, social, and health aspects. The reuse and recycling of by-products represents a very important issue: for this reason, the development of innovative recovery and extraction methodologies must be mandatory. In this context of a circular economy, the study of green extraction techniques also becomes a priority in substitution of traditional extraction approaches. This review is focused on the recovery of chlorogenic acids from agri-food wastes, as these compounds have an important impact on human health, exhibiting several different and important healthy properties. Novel extraction methodologies, namely microwave and ultrasound-assisted extractions, supercritical fluid extraction, and pressurized-liquid extraction, are discussed here, in comparison with conventional techniques. The great potentialities of these new innovative green and sustainable approaches are pointed out. Further investigations and optimization are mandatory before their application in industrial processes.
Quantifying Conformational Isomerism in Chain Molecules by Linear Raman Spectroscopy: The Case of Methyl Esters
Authors: Gawrilow Maxim , Suhm Martin A.
Published: July 2021

The conformational preferences of the ester group have the potential to facilitate the large amplitude folding of long alkyl chains in the gas phase. They are monitored by Raman spectroscopy in supersonic jet expansions for the model system methyl butanoate, after establishing a quantitative relationship with quantum–chemical predictions for methyl methanoate. This requires a careful analysis of experimental details, and a simulation of the rovibrational contours for near-symmetric top molecules. The technique is shown to be complementary to microwave spectroscopy in quantifying coexisting conformations. It confirms that a C−O−C(=O)–C–C chain segment can be collapsed into a single all-trans conformation by collisional cooling, whereas alkyl chain isomerism beyond this five-membered chain largely survives the jet expansion. This sets the stage for the investigation of linear alkyl alkanoates in terms of dispersion-induced stretched-chain to hairpin transitions by Raman spectroscopy.
Assessment of Immune Response and Efficacy of Essential Oils Application on Controlling Necrotic Enteritis Induced by Clostridium perfringens in Broiler Chickens
Authors: Gharaibeh Mohammad H. , Khalifeh Mohammad S. , Nawasreh Adi N. , Hananeh Wael M. , Awawdeh Mofleh S.
Published: July 2021

Necrotic enteritis (NE) caused by Clostridium perfringens is one of the most important enteric diseases in poultry. The antibacterial activity of two different essential oil (EO) blends against C. perfringens was investigated both in vitro and in vivo. Additionally, the immunological response to EO treatment was assessed. In the in vitro study, the antibacterial activity of EO formulas and commonly used antibiotics was evaluated against C. perfringens using disk diffusion assay, minimum inhibitory concentration (MIC) assay, and minimum bactericidal concentration (MBC) assay. In the in vivo study, NE experimental infection was performed on 440 Ross broiler chicks at 19 days of age for 4 continuous days. The chicks were treated with either EOs or amoxicillin at 22 days of age for 5 continuous days. One day after the end of treatment, the birds’ performance was evaluated by calculating the feed conversion ratio. Serum samples from 120 birds were collected to measure the levels of IL-1β, IFN-γ, IL-8, IL-10, and IL-17. After that, all birds were slaughtered, and their small intestines were subjected to gross and histopathological evaluation. In addition, bacterial counts in the small intestines were evaluated. In the in vitro study, EOs showed higher antimicrobial activities in comparison with antibiotics against C. perfringens. In the in vivo study, birds treated with EOs showed a significant decrease in bacterial counts, a significant decrease in intestinal lesions, and a significant improvement in performance compared with untreated birds (p < 0.05). Moreover, treating birds with EOs directed the immune system toward an anti-inflammatory pathway. None of the treated birds died due to NE compared with the 10% mortality rate in untreated birds. In conclusion, EOs might be an effective and safe alternative to antibiotics in the treatment of chicken NE.
Phenolic Constituents from Platycodon grandiflorum Root and Their Anti-Inflammatory Activity
Authors: Li Wei , Yang Hye Jin
Published: July 2021

Six lignols (1–6), including two new compounds (+)-(7R,8R)-palmitoyl alatusol D (1) and (+)-(7R,8R)-linoleyl alatusol D (2), along with four phenolics (7–10), a neolignan (11), three alkyl aryl ether-type lignans (12–14), two furofuran-type lignans (15–16), three benzofuran-type lignans (17–19), a tetrahydrofuran-type lignan (20), and a dibenzylbutane-type lignan (21) were isolated from the ethyl acetate-soluble fraction of the methanol extract of Platycodon grandiflorum (Jacq.) A. DC. root. The chemical structures of the obtained compounds were elucidated via high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy analyses. The obtained spectroscopic data agreed well with literature. Among the isolated compounds, eighteen (1–7 and 11–21) were isolated from P. grandiflorum and the Campanulaceae family for the first time. This is the first report on lignol and lignan components of P. grandiflorum. The anti-inflammatory effects of the isolated compounds were examined in terms of their ability to inhibit the production of pro-inflammatory cytokines IL-6, IL-12 p40, and TNF-α in lipopolysaccharide-stimulated murine RAW264.7 macrophage cells. Nine compounds (4–6, 12, and 15–19) exhibited inhibitory effects on IL-12 p40 production, eleven compounds (1–6, 12, 15–17, and 19) exhibited inhibitory activity on IL-6 production, and eleven compounds (1–6 and 15–19) exhibited inhibitory effects against TNF-α. These results warrant further investigation into the potential anti-inflammatory activity and general benefits of the phenolic constituents of P. grandiflorum root.
2D Slab Models of Nanotubes Based on Tetragonal TiO2 Structures: Validation over a Diameter Range
Authors: Lisovski Oleg , Piskunov Sergei , Bocharov Dmitry , Kenmoe Stephane
Published: July 2021

One-dimensional nanomaterials receive much attention thanks to their advantageous properties compared to simple, bulk materials. A particular application of 1D nanomaterials is photocatalytic hydrogen generation from water. Such materials are studied not only experimentally, but also computationally. The bottleneck in computations is insufficient computational power to access realistic systems, especially with water or another adsorbed species, using computationally expensive methods, such as ab initio MD. Still, such calculations are necessary for an in-depth understanding of many processes, while the available approximations and simplifications are either not precise or system-dependent. Two-dimensional models as an approximation for TiO2 nanotubes with (101) and (001) structures were proposed by our group for the first time in Comput. Condens. Matter journal in 2018. They were developed at the inexpensive DFT theory level. The principle was to adopt lattice constants from an NT with a specific diameter and keep them fixed in the 2D model optimization, with geometry modifications for one of the models. Our previous work was limited to studying one configuration of a nanotube per 2D model. In this article one of the models was chosen and tested for four different configurations of TiO2 nanotubes: (101) (n,0), (101) (0,n), (001) (n,0), and (001) (0,n). All of them are 6-layered and have rectangular unit cells of tetragonal anatase form. Results of the current study show that the proposed 2D model is indeed universally applicable for different nanotube configurations so that it can be useful in facilitating computationally costly calculations of large systems with adsorbates.
Nanostructured Gas Sensors: From Air Quality and Environmental Monitoring to Healthcare and Medical Applications
Authors: Chen Xiaohu , Leishman Michelle , Bagnall Darren , Nasiri Noushin
Published: July 2021

In the last decades, nanomaterials have emerged as multifunctional building blocks for the development of next generation sensing technologies for a wide range of industrial sectors including the food industry, environment monitoring, public security, and agricultural production. The use of advanced nanosensing technologies, particularly nanostructured metal-oxide gas sensors, is a promising technique for monitoring low concentrations of gases in complex gas mixtures. However, their poor conductivity and lack of selectivity at room temperature are key barriers to their practical implementation in real world applications. Here, we provide a review of the fundamental mechanisms that have been successfully implemented for reducing the operating temperature of nanostructured materials for low and room temperature gas sensing. The latest advances in the design of efficient architecture for the fabrication of highly performing nanostructured gas sensing technologies for environmental and health monitoring is reviewed in detail. This review is concluded by summarizing achievements and standing challenges with the aim to provide directions for future research in the design and development of low and room temperature nanostructured gas sensing technologies.
Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage
Authors: Valdiglesias Vanessa , Fernández-Bertólez Natalia , Lema-Arranz Carlota , Rodríguez-Fernández Raquel , Pásaro Eduardo , Reis Ana Teresa , Teixeira João Paulo , Costa Carla , Laffon Blanca
Published: July 2021

Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.
Revisiting the Vital Drivers and Mechanisms of β-Glucan Masking in Human Fungal Pathogen, Candida albicans
Authors: Hameed Saif , Hans Sandeep , Singh Shweta , Dhiman Ruby , Monasky Ross , Pandey Ramendra Pati , Thangamani Shankar , Fatima Zeeshan
Published: July 2021

Among the several human fungal pathogens, Candida genus represents one of the most implicated in the clinical scenario. There exist several distinctive features that govern the establishment of Candida infections in addition to their capacity to adapt to multiple stress conditions inside humans which also include evasion of host immune responses. The complex fungal cell wall of the prevalent pathogen, Candida albicans, is one of the main targets of antifungal drugs and recognized by host immune cells. The wall consists of tiered arrangement of an outer thin but dense covering of mannan and inner buried layers of β-glucan and chitin. However, the pathogenic fungi adopt strategies to evade immune recognition by masking these molecules. This capacity to camouflage the immunogenic polysaccharide β-glucan from the host is a key virulence factor of C. albicans. The present review is an attempt to collate various underlying factors and mechanisms involved in Candida β-glucan masking from the available pool of knowledge and provide a comprehensive understanding. This will further improve therapeutic approaches to candidiasis by identifying new antifungal targets that blocks fungal immune evasion.
Enhanced Bioavailability of AC1497, a Novel Anticancer Drug Candidate, via a Self-Nanoemulsifying Drug Delivery System
Authors: Baral Kshitis Chandra , Song Jae-Geun , Lee Sang Hoon , Bajracharya Rajiv , Sreenivasulu Godesi , Kim Minkyoung , Lee Kyeong , Han Hyo-Kyung
Published: July 2021

AC1497 is an effective dual inhibitor of malate dehydrogenase 1 and 2 targeting cancer metabolism. However, its poor aqueous solubility results in low bioavailability, limiting its clinical development. This study was conducted to develop an effective self-nanoemulsifying drug delivery system (SNEDDS) of AC1497 to improve its oral absorption. Based on the solubility of AC1497 in various oils, surfactants, and cosurfactants, Capryol 90, Kolliphor RH40, and Transcutol HP were selected as the components of SNEDDS. After testing various weight ratios of Capryol 90 (20–30%), Kolliphor RH40 (35–70%), and Transcutol HP (10–35%), SNEDDS-F4 containing 20% Capryol 90, 45% Kolliphor RH40, and 35% Transcutol HP was identified as an optimal SNEDDS with a narrow size distribution (17.8 ± 0.36 nm) and high encapsulation efficiency (93.6 ± 2.28%). Drug release from SNEDDS-F4 was rapid, with approximately 80% of AC1497 release in 10 min while the dissolution of the drug powder was minimal (<2%). Furthermore, SNEDDS-F4 significantly improved the oral absorption of AC1497 in rats. The maximum plasma concentration and area under the plasma concentration–time curve of AC1497 were, respectively 6.82- and 3.14-fold higher for SNEDDS-F4 than for the drug powder. In conclusion, SNEDDS-F4 with Capryol 90, Kolliphor RH40, and Transcutol HP (20:45:35, w/w) effectively improves the solubility and oral absorption of AC1497.
Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
Authors: Botti Giada , Dalpiaz Alessandro , Pavan Barbara
Published: July 2021

About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejection from the brain after permeation across the blood brain barrier (BBB). Currently, the prodrug approach has greatly evolved in comparison to lipidization. This review describes the evolution of the prodrug approach for brain targeting considering the design of prodrugs as active influx substrates or molecules able to inhibit or elude AETs. Moreover, the prodrug approach appears strategic in optimization of the encapsulation of neuroactive drugs in nanoparticulate systems that can be designed to induce their receptor-mediated transport (RMT) across the BBB by appropriate decorations on their surface. Nasal administration is described as a valuable alternative to obtain the brain targeting of drugs, evidencing that the prodrug approach can allow the optimization of micro or nanoparticulate nasal formulations of neuroactive agents in order to obtain this goal. Furthermore, nasal administration is also proposed for prodrugs characterized by peripheral instability but potentially able to induce their targeting inside cells of the brain.
Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery
Authors: Tang Lu , Li Jing , Zhao Qingqing , Pan Ting , Zhong Hui , Wang Wei
Published: July 2021

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.
Overexpression of Douglas-Fir LEAFY COTYLEDON1 (PmLEC1) in Arabidopsis Induces Embryonic Programs and Embryo-like Structures in the lec1-1 Mutant but Not in Wild Type Plants
Authors: Vetrici Mariana A. , Yevtushenko Dmytro P. , Misra Santosh
Published: July 2021

Somatic embryogenesis (SE) is the most promising method for the quick propagation of desirable plant genotypes. However, application of SE to conifers remains challenging due to our limited knowledge about the genes involved in embryogenesis and the processes that lead to somatic embryo formation. Douglas-fir, an economically important lumber species, possesses a homolog of the angiosperm embryo-regulatory LEC1 gene. In the present study, we analyzed the potential of Douglas-fir PmLEC1 to induce embryonic programs in the vegetative cells of a heterologous host, Arabidopsis thaliana. PmLEC1 complemented the Arabidopsis lec1-1 null mutant and led to a variety of phenotypes ranging from normal morphology to developmental arrest at various stages in the T1 generation. PmLEC1 did not affect the morphology of wild type Arabidopsis T1 plants. More profound results occurred in T2 generations. PmLEC1 expression induced formation of recurrent somatic embryo-like structures in vegetative tissues of the rescued lec1-1 mutant but loss of apical dominance (bushy phenotype) in wild type plants. The activation of embryonic programs in the lec1-1PmLEC1 T2 plants was confirmed by the presence of the embryo-specific transcripts, OLEOSIN and CRUCIFERIN. In contrast, no embryo-like structures, and no OLEOSIN or CRUCIFERIN were observed in PmLEC1-expressing bushy wild type T2 plants.
Activity of Anthracenediones and Flavoring Phenols in Hydromethanolic Extracts of Rubia tinctorum against Grapevine Phytopathogenic Fungi
Authors: Langa-Lomba Natalia , Sánchez-Hernández Eva , Buzón-Durán Laura , González-García Vicente , Casanova-Gascón José , Martín-Gil Jesús , Martín-Ramos Pablo
Published: July 2021

In this work, the chemical composition of Rubia tinctorum root hydromethanolic extract was analyzed by GC–MS, and over 50 constituents were identified. The main phytochemicals were alizarin-related anthraquinones and flavoring phenol compounds. The antifungal activity of this extract, alone and in combination with chitosan oligomers (COS) or with stevioside, was evaluated against the pathogenic taxa Diplodia seriata, Dothiorella viticola and Neofusicoccum parvum, responsible for the so-called Botryosphaeria dieback of grapevine. In vitro mycelial growth inhibition tests showed remarkable activity for the pure extract, with EC50 and EC90 values as low as 66 and 88 μg·mL−1, respectively. Nonetheless, enhanced activity was attained upon the formation of conjugate complexes with COS or with stevioside, with synergy factors of up to 5.4 and 3.3, respectively, resulting in EC50 and EC90 values as low as 22 and 56 μg·mL−1, respectively. The conjugate with the best performance (COS-R. tinctorum extract) was then assayed ex situ on autoclaved grapevine wood against D. seriata, confirming its antifungal behavior on this plant material. Finally, the same conjugate was evaluated in greenhouse assays on grafted grapevine plants artificially inoculated with the three aforementioned fungal species, resulting in a significant reduction in the infection rate in all cases. This natural antifungal compound represents a promising alternative for developing sustainable control methods against grapevine trunk diseases.
Metabolomic Evaluation of Tissue-Specific Defense Responses in Tomato Plants Modulated by PGPR-Priming against Phytophthora capsici Infection
Authors: Mhlongo Msizi I. , Piater Lizelle A. , Steenkamp Paul A. , Labuschagne Nico , Dubery Ian A.
Published: July 2021

Plant growth-promoting rhizobacteria (PGPR) can stimulate disease suppression through the induction of an enhanced state of defense readiness. Here, untargeted ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS) and targeted ultra-high performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC–QqQ-MS) were used to investigate metabolic reprogramming in tomato plant tissues in response to priming by Pseudomonas fluorescens N04 and Paenibacillus alvei T22 against Phytophthora capsici. Roots were treated with the two PGPR strains prior to stem inoculation with Ph. capsici. Metabolites were methanol-extracted from roots, stems and leaves at two–eight days post-inoculation. Targeted analysis by UHPLC–QqQ-MS allowed quantification of aromatic amino acids and phytohormones. For untargeted analysis, UHPLC–MS data were chemometrically processed to determine signatory biomarkers related to priming against Ph. capsici. The aromatic amino acid content was differentially reprogrammed in Ps. fluorescens and Pa. alvei primed plants responding to Ph. capsici. Furthermore, abscisic acid and methyl salicylic acid were found to be major signaling molecules in the tripartite interaction. LC–MS metabolomics analysis showed time-dependent metabolic changes in the primed-unchallenged vs. primed-challenged tissues. The annotated metabolites included phenylpropanoids, benzoic acids, glycoalkaloids, flavonoids, amino acids, organic acids, as well as oxygenated fatty acids. Tissue-specific reprogramming across diverse metabolic networks in roots, stems and leaves was also observed, which demonstrated that PGPR priming resulted in modulation of the defense response to Ph. capsici infection.
Microbial Biostimulants as Response to Modern Agriculture Needs: Composition, Role and Application of These Innovative Products
Authors: Castiglione Adele M. , Mannino Giuseppe , Contartese Valeria , Bertea Cinzia M. , Ertani Andrea
Published: July 2021

An increasing need for a more sustainable agriculturally-productive system is required in order to preserve soil fertility and reduce soil biodiversity loss. Microbial biostimulants are innovative technologies able to ensure agricultural yield with high nutritional values, overcoming the negative effects derived from environmental changes. The aim of this review was to provide an overview on the research related to plant growth promoting microorganisms (PGPMs) used alone, in consortium, or in combination with organic matrices such as plant biostimulants (PBs). Moreover, the effectiveness and the role of microbial biostimulants as a biological tool to improve fruit quality and limit soil degradation is discussed. Finally, the increased use of these products requires the achievement of an accurate selection of beneficial microorganisms and consortia, and the ability to prepare for future agriculture challenges. Hence, the implementation of the microorganism positive list provided by EU (2019/1009), is desirable.
Selenium Fortification Alters the Growth, Antioxidant Characteristics and Secondary Metabolite Profiles of Cauliflower (Brassica oleracea var. botrytis) Cultivars in Hydroponic Culture
Authors: Saeedi Mahboobeh , Soltani Forouzandeh , Babalar Mesbah , Izadpanah Fatemeh , Wiesner-Reinhold Melanie , Baldermann Susanne
Published: July 2021

Nowadays the importance of selenium for human health is widely known, but most of the plants are poor in terms of selenium storage and accumulation because of the low selenium mineralization potential of the soil. For this purpose, foliar application of different sodium selenate concentrations (0, 5, 10, 15, 20 mg/L) was used to treat the cauliflower cultivars “Clapton” and “Graffiti”. Higher yields and other related vegetative attributes were improved at 10 and 15 mg/L sodium selenate application. At a concentration of 10 mg/L sodium selenate, photosynthetic pigments, total phenolic compounds and antioxidant capacity were enhanced in both cultivars, but the “Graffiti” cultivar responded stronger than the “Clapton” cultivar. The glucosinolates were accumulated in response to selenium fortification and the highest amounts were found in the “Graffiti” cultivar at 10 mg/L. Selenium accumulated concentration-dependently and rose with higher fertilization levels. In general, foliar application of selenium at 10 mg/L led to an accumulation of secondary metabolites and also positively affected the growth and yield of florets.
Micellar Assembly and Disassembly of Organoselenium Block Copolymers through Alkylation and Dealkylation Processes
Authors: Eom Taejun , Khan Anzar
Published: July 2021

The aim of this work is to demonstrate that the alkylation and dealkylation of selenium atoms is an effective tool in controlling polymer amphiphilicity and, hence, its assembly and disassembly process in water. To establish this concept, poly(ethylene glycol)-block-poly(glycidyl methacrylate) was prepared. A post-synthesis modification with phenyl selenolate through a base-catalyzed selenium-epoxy ‘click’ reaction then gave rise to the side-chain selenium-containing block copolymer with an amphiphilic character. This polymer assembled into micellar structures in water. However, silver tetrafluoroborate-promoted alkylation of the selenium atoms resulted in the formation of hydrophilic selenonium tetrafluoroborate salts. This enhancement in the chemical polarity of the second polymer block removed the amphiphilic character from the polymer chain and led to the disassembly of the micellar structures. This process could be reversed by restoring the original amphiphilic polymer character through the dealkylation of the cations.
Investigating Physio-Thermo-Mechanical Properties of Polyurethane and Thermoplastics Nanocomposite in Various Applications
Authors: Allami Tyser , Alamiery Ahmed , Nassir Mohamed H. , Kadhum Amir H.
Published: July 2021

The effect of the soft and hard polyurethane (PU) segments caused by the hydrogen link in phase-separation kinetics was studied to investigate the morphological annealing of PU and thermoplastic polyurethane (TPU). The significance of the segmented PUs is to achieve enough stability for further applications in biomedical and environmental fields. In addition, other research focuses on widening the plastic features and adjusting the PU–polyimide ratio to create elastomer of the poly(urethane-imide). Regarding TPU- and PU-nanocomposite, numerous studies investigated the incorporation of inorganic nanofillers such as carbon or clay to incorporating TPU-nanocomposite in several applications. Additionally, the complete exfoliation was observed up to 5% and 3% of TPU–clay modified with 12 amino lauric acid and benzidine, respectively. PU-nanocomposite of 5 wt.% Cloisite®30B showed an increase in modulus and tensile strength by 110% and 160%, respectively. However, the nanocomposite PU-0.5 wt.% Carbone Nanotubes (CNTs) show an increase in the tensile modulus by 30% to 90% for blown and flat films, respectively. Coating PU influences stress-strain behavior because of the interaction between the soft segment and physical crosslinkers. The thermophysical properties of the TPU matrix have shown two glass transition temperatures (Tg’s) corresponding to the soft and the hard segment. Adding a small amount of tethered clay shifts Tg for both segments by 44 °C and 13 °C, respectively, while adding clay from 1 to 5 wt.% results in increasing the thermal stability of TPU composite from 12 to 34 °C, respectively. The differential scanning calorimetry (DSC) was used to investigate the phase structure of PU dispersion, showing an increase in thermal stability, solubility, and flexibility. Regarding the electrical properties, the maximum piezoresistivity (10 S/m) of 7.4 wt.% MWCNT was enhanced by 92.92%. The chemical structure of the PU–CNT composite has shown a degree of agglomeration under disruption of the sp2 carbon structure. However, with extended graphene loading to 5.7 wt.%, piezoresistivity could hit 10−1 S/m, less than 100 times that of PU. In addition to electrical properties, the acoustic behavior of MWCNT (0.35 wt.%)/SiO2 (0.2 wt.%)/PU has shown sound absorption of 80 dB compared to the PU foam sample. Other nanofillers, such as SiO2, TiO2, ZnO, Al2O3, were studied showing an improvement in the thermal stability of the polymer and enhancing scratch and abrasion resistance.
A Bacteria and Cell Repellent Zwitterionic Polymer Coating on Titanium Base Substrates towards Smart Implant Devices
Authors: Es-Souni Mona , Es-Souni Martha , Bakhti Hamzah , Gülses Aydin , Fischer-Brandies Helge , Açil Yahya , Wiltfang Jörg , Flörke Christian
Published: July 2021

Biofouling and biofilm formation on implant surfaces are serious issues that more than often lead to inflammatory reactions and the necessity of lengthy post-operation treatments or the removal of the implant, thus entailing a protracted healing process. This issue may be tackled with a biocompatible polymeric coating that at the same time prevents biofouling. In this work, oxygen plasma-activated silanized titanium substrates are coated with poly(sulfobetaine methacrylate), a zwitterionic antibiofouling polymer, using photopolymerization. The characterization of polymer films includes FT-IR, AFM, and adhesion strength measurements, where adhesion strength is analyzed using a cylindrical flat punch indenter and water contact angle (WCA) measurements. Both cytotoxicity analysis with primary human fibroblasts and fluorescence microscopy with fibroblasts and plaque bacteria are also performed is this work, with each procedure including seeding on coated and control surfaces. The film morphology obtained by the AFM shows a fine structure akin to nanoropes. The coatings can resist ultrasonic and sterilization treatments. The adhesion strength properties substantially increase when the films are soaked in 0.51 M of NaCl prior to testing when compared to deionized water. The coatings are superhydrophilic with a WCA of 10° that increases to 15° after dry aging. The viability of fibroblasts in the presence of coated substrates is comparable to that of bare titanium. When in direct contact with fibroblasts or bacteria, marginal adhesion for both species occurs on coating imperfections. Because photopolymerization can easily be adapted to surface patterning, smart devices that promote both osseointegration (in non-coated areas) and prevent cell overgrowth and biofilm formation (in coated areas) demonstrate practical potential.
Improved Mechanical, Thermal, and Hydrophobic Properties of PLA Modified with Alkoxysilanes by Reactive Extrusion Process
Authors: Torres Elena , Gaona Aide , García-Bosch Nadia , Muñoz Miguel , Fombuena Vicent , Moriana Rosana , Vallés-Lluch Ana
Published: July 2021

An eco-friendly strategy for the modification of polylactic acid (PLA) surface properties, using a solvent-free process, is reported. Reactive extrusion (REX) allowed the formation of new covalent bonds between functional molecules and the PLA polymeric matrix, enhancing its mechanical properties and modifying surface hydrophobicity. To this end, the PLA backbone was modified using two alkoxysilanes, phenyltriethoxysilane and N-octyltriethoxysilane. The reactive extrusion process was carried out under mild conditions, using melting temperatures between 150 and 180 °C, 300 rpm as screw speed, and a feeding rate of 3 kg·h−1. To complete the study, flat tapes of neat and functionalized PLA were obtained through monofilament melt extrusion to quantify the enhancement of mechanical properties and hydrophobicity. The results verified that PLA modified with 3 wt% of N-octyltriethoxysilane improves mechanical and thermal properties, reaching Young’s modulus values of 4.8 GPa, and PLA hydrophobic behavior, with values of water contact angle shifting from 68.6° to 82.2°.