bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Wear Simulation Methodology for Predicting Nonlinear Wear Behavior of Tools in Sheet Metal Forming
Authors: Bang Junho , Kim Minki , Bae Gihyun , Kim Hong-Gee , Lee Myoung-Gyu , Song Junghan
Published: June 2022

In conventional wear simulation, the geometry must be updated for succeeding iterations to predict the accumulated wear. However, repeating this procedure up to the desired iteration is rather time consuming. Thus, a wear simulation process capable of reasonable quantitative wear prediction in reduced computational time is needed. This study aimed to develop an efficient wear simulation method to predict quantitative wear reasonably in reduced computational time without updating the geometry for succeeding iterations. The wear resistance of a stamping tool was quantitatively evaluated for different punch shapes (R3.0 and R5.5) and coating conditions (physical vapor deposition of CrN and AlTiCrN coatings) by using a progressive die set. To capture the nonlinear wear behavior with respect to strokes, a nonlinear equation from a modified form of Archard’s wear model was proposed. By utilizing the scale factor representing the changes in wear properties with respect to wear depth as input, the simulation can predict the behavior of rapidly increasing wear depth with respect to strokes after failure initiation. Furthermore, the proposed simulation method is efficient in terms of computational time because it does not need to perform geometry updates.
A Systematic Review of the Research Development on the Application of Machine Learning for Concrete
Authors: Khan Kaffayatullah , Ahmad Waqas , Amin Muhammad Nasir , Ahmad Ayaz
Published: June 2022

Research on the applications of new techniques such as machine learning is advancing rapidly. Machine learning methods are being employed to predict the characteristics of various kinds of concrete such as conventional concrete, recycled aggregate concrete, geopolymer concrete, fiber-reinforced concrete, etc. In this study, a scientometric-based review on machine learning applications for concrete was performed in order to evaluate the crucial characteristics of the literature. Typical review studies are limited in their capacity to link divergent portions of the literature systematically and precisely. Knowledge mapping, co-citation, and co-occurrence are among the most challenging aspects of innovative studies. The Scopus database was chosen for searching for and retrieving the data required to achieve the study’s aims. During the data analysis, the relevant sources of publications, relevant keywords, productive writers based on publications and citations, top articles based on citations received, and regions actively engaged in research into machine learning applications for concrete were identified. The citation, bibliographic, abstract, keyword, funding, and other data from 1367 relevant documents were retrieved and analyzed using the VOSviewer software tool. The application of machine learning in the construction sector will be advantageous in terms of economy, time-saving, and reduced requirement for effort. This study can aid researchers in building joint endeavors and exchanging innovative ideas and methods, due to the statistical and graphical portrayal of participating authors and countries.
Numerical Simulation and Process Optimization on Hot Twist-Stretch Straightening of Ti-6Al-4V Alloy Profile
Authors: Deng Xuwen , Hui Songxiao , Ye Wenjun , Liu Rui , Huang Liang
Published: June 2022

Ti-6Al-4V profiles prepared by hot extrusion are usually accompanied by bending and twisting. The hot twist-stretch straightening is an effective strategy such that the bending deflection and twisting angle can be simultaneously decreased by a single straightening process. In addition, utilizing stress relaxation effect, the residual stress and springback can be greatly reduced by holding the straightening temperature and strain constant for a period after twist-stretch straightening. In this study, the hot deformation behaviors of the Ti-6Al-4V profile were revealed by experiments. The tensile model was obtained by uniaxial tensile tests within ranges of temperatures (500–700 °C) and strain rates (5 × 10−5–1 × 10−3 s−1). The creep constitutive model was acquired with stress relaxation experiments in ranges of temperatures (500–700 °C) and pre-strain of 1.5%. Then, the coupled thermo-mechanical model of hot twist-stretch straightening was established. Based on orthogonal experiment strategy, the effects of straightening temperature, stretch strain, and holding time on the bending deflection and torsion angle of profile were investigated systematically and the process was optimized. The straightening accuracy is significantly affected by straightening temperature and holding time. By using optimized process parameters in practical straightening experiments, the deflection/length and angle/length after straightening does not exceed 2‰ and 2.5‰°/mm, respectively, which is basically consistent with the numerical simulation result.
Low-Density Particleboards Modified with Blowing Agents—Characteristic and Properties
Authors: Boruszewski Piotr , Borysiuk Piotr , Jankowska Agnieszka , Pazik Jolanta
Published: June 2022

Although lightweight particleboards have been commercially available for years, they still have a number of disadvantages, including difficulty to process, brittleness, low impact strength, and other mechanical resistance. The aim of the paper was to determine the possibility of producing particleboards of reduced density (dedicated for furniture industry) as a result of using blowing agents from the group of hydrazides, dicarboxamides, or tetrazoles, which were modifiers of the adhesive resin used for bonding the particles of the core layer of three-layer particleboards. The concept presents the possibility of producing low-density particleboards in a standard technological process by modifying the adhesive resin, which has not been practiced by others until now. Analysis of the results of testing the particleboards properties with various types of modifiers (blowing agents), glue content (high 10%/12% and low 8%/10%), differing in glue dosing method, and different particle sizes allowed concluding that the most satisfactory effect was found in particleboards made of the variant modified with p-toluenesulfonyl hydrazide. This variant was characterised by the highest mechanical properties (bending strength, modulus elasticity, and internal bond strength) with high dimensional stability. The presented technology proposal can be applied in the industry.
Multidisciplinary Approach to Agricultural Biomass Ash Usage for Earthworks in Road Construction
Authors: Barišić Ivana , Netinger Grubeša Ivanka , Hackenberger Davorka K. , Palijan Goran , Glavić Stella , Trkmić Marija
Published: June 2022

Agricultural biomass has great bioenergy potential due to its availability, and it is a carbon-free energy source. During biomass incineration, biomass ash is formed, which is still considered as a waste without proper disposal and management solutions. Various biomass ash utilization options were investigated, mainly concerning engineering issues (the mechanical characterization of newly produced building materials or products), and there is a lack of knowledge of environmental issues arising from this “waste” material utilization in civil engineering practice. The main aim of this research is discussion of a different agricultural biomass characteristics as a fuel, the impact of agricultural biomass ashes (ABA) on the mechanical properties of stabilized soil with a particular emphasis on the environmental impacts within this kind of waste management. The results of this study indicate improved geotechnical characteristics of low-plasticity clay stabilized by lime/ABA binder. In addition to mechanical characterization for materials embedded in road embankments and subgrades, appropriate environmental risk assessment needs to be performed, and the results of this study indicate that the amount of ABAs added to the soil for roadworks should not have adverse effects on the soil fauna in the surrounding environment.
Eco-Friendly Extraction, Structure, and Gel Properties of ι-Carrageenan Extracted Using Ca(OH)2
Authors: Jiang Feng , Liu Yao , Xiao Qiong , Chen Fuquan , Weng Huifen , Chen Jun , Zhang Yonghui , Xiao Anfeng
Published: June 2022

An eco-friendly method for ι-carrageenan extraction from seaweed Eucheuma denticulatum through boiling and using a low concentration of Ca(OH)2 is reported. Compared to the traditional method of ι-carrageenan extraction using NaOH, the reported method using Ca(OH)2 had the advantages of using 93.3% less alkali and 86.8% less water, having a 25.0% shorter total extraction time, a 17.6% higher yield, and a 43.3% higher gel strength of the product. In addition, we evaluated the gel properties and structures of ι-carrageenan products extracted by Ca(OH)2 (Ca-IC) and NaOH (Na-IC). The Fourier transform infrared spectroscopy results showed that the structures of Ca-IC and Na-IC did not change remarkably. The results of the thermogravimetric analysis and differential scanning calorimetry showed that Ca-IC had the same thermal stability as Na-IC. The results of the textural analysis showed that Ca-IC had a higher hardness and better chewiness compared to Na-IC. Rheological results indicated that Ca-IC and Na-IC exhibited shear-thinning and non-Newtonian fluid properties, whereas the viscosity of Ca-IC was less than that of Na-IC. In conclusion, this new method of ι-carrageenan extraction using Ca-IC is markedly better and yields higher quality carrageenan than the conventional method of using Na-IC.
A Review on Removal and Destruction of Per- and Polyfluoroalkyl Substances (PFAS) by Novel Membranes
Authors: Das Suman , Ronen Avner
Published: June 2022

Per- and Polyfluoroalkyl Substances (PFAS) are anthropogenic chemicals consisting of thousands of individual species. PFAS consists of a fully or partly fluorinated carbon–fluorine bond, which is hard to break and requires a high amount of energy (536 kJ/mole). Resulting from their unique hydrophobic/oleophobic nature and their chemical and mechanical stability, they are highly resistant to thermal, chemical, and biological degradation. PFAS have been used extensively worldwide since the 1940s in various products such as non-stick household items, food-packaging, cosmetics, electronics, and firefighting foams. Exposure to PFAS may lead to health issues such as hormonal imbalances, a compromised immune system, cancer, fertility disorders, and adverse effects on fetal growth and learning ability in children. To date, very few novel membrane approaches have been reported effective in removing and destroying PFAS. Therefore, this article provides a critical review of PFAS treatment and removal approaches by membrane separation systems. We discuss recently reported novel and effective membrane techniques for PFAS separation and include a detailed discussion of parameters affecting PFAS membrane separation and destruction. Moreover, an estimation of cost analysis is also included for each treatment technology. Additionally, since the PFAS treatment technology is still growing, we have incorporated several future directions for efficient PFAS treatment.
Sampling and Analysis of Low-Molecular-Weight Volatile Metabolites in Cellular Headspace and Mouse Breath
Authors: Issitt Theo , Sweeney Sean T. , Brackenbury William J. , Redeker Kelly R.
Published: June 2022

Volatile compounds, abundant in breath, can be used to accurately diagnose and monitor a range of medical conditions. This offers a noninvasive, low-cost approach with screening applications; however, the uptake of this diagnostic approach has been limited by conflicting published outcomes. Most published reports rely on large scale screening of the public, at single time points and without reference to ambient air. Here, we present a novel approach to volatile sampling from cellular headspace and mouse breath that incorporates multi-time-point analysis and ambient air subtraction revealing compound flux as an effective proxy of active metabolism. This approach to investigating breath volatiles offers a new avenue for disease biomarker discovery and diagnosis. Using gas chromatography mass spectrometry (GC/MS), we focus on low molecular weight, metabolic substrate/by-product compounds and demonstrate that this noninvasive technique is sensitive (reproducible at ~1 µg cellular protein, or ~500,000 cells) and capable of precisely determining cell type, status and treatment. Isolated cellular models represent components of larger mammalian systems, and we show that stress- and pathology-indicative compounds are detectable in mice, supporting further investigation using this methodology as a tool to identify volatile targets in human patients.
Analysis of Compliance and Kinetostatic of a Novel Class of n-4R Compliant Parallel Micro Pointing Mechanism
Authors: Ren Jun , Li Qiliang
Published: June 2022

A novel class of n-4R compliant parallel pointing mechanisms is proposed, and the compliance and kinetostatic model of the mechanism are established and analyzed successively. Firstly, the compliance model of a class of n-4R compliant parallel pointing mechanism is established based on the coordinate transformation. The model is verified by finite element analysis, and the influence of geometric parameter variations on the compliance performance of the mechanism is analyzed. Secondly, the mechanism is simplified to an equivalent spring system, and the governing equation of the equivalent spring system is constructed by utilizing the established compliance model. According to the governing equation, the mapping relationship between the input force and the output displacement of the mechanism is subsequently obtained, that is, the kinetostatic model. Then, the accuracy of the kinetostatic model is verified by two simulation examples: The spiral trajectory of the mobile platform center and the spatial pointing trajectory of the mechanism. The results of the two examples show that the deviations between the analytical results and the FE-results are within 0.038% and 0.857%, with the excellent consistency indicating the accuracy of the kinetostatic model. Finally, the influence of the geometric parameter values on the mapping matrix in the kinetostatic model is studied.
High Sensitivity Fiber Interferometric Strain Sensors Based on Elongated Fiber Abrupt Tapers
Authors: Zhou Haimiao , Peng Ya-Pei , Chen Nan-Kuang
Published: June 2022

We demonstrate high-sensitivity fiber strain sensors based on an elongated abrupt taper. The fiber abrupt taper, with a tapered diameter ranging from 40–60 μm, was made by using a hydrogen microflame to break the waveguide adiabaticity so as to convert the fundamental mode into cladding modes. The abrupt taper was further uniformly tapered by using a normal moving flame with a torch diameter of 7 mm to elongate the tapered region until the tapered diameter was down to 2.5–5 μm. The excited high-order modes were confined to propagate along the cladding and then recombined at the rear edge of the fiber taper to produce interferences with extinction ratios of up to 16 dB. The tapered region was pulled outwardly to change the optical path difference (OPD) between modes to measure the tensile strain with all the interfering wavelengths blue-shifted. The measured best strain sensitivity was 116.21 pm/με and the coefficient of determination R2 of linear fitting exhibits high linearity. This strain sensor based on elongated abrupt taper is several times higher than that of most of the fiber strain sensors ever reported.
Oscillator-Network-Based Ising Machine
Authors: Zhang Yi , Deng Yi , Lin Yinan , Jiang Yang , Dong Yujiao , Chen Xi , Wang Guangyi , Shang Dashan , Wang Qing , Yu Hongyu , Wang Zhongrui
Published: June 2022

With the slowdown of Moore’s law, many emerging electronic devices and computing architectures have been proposed to sustain the performance advancement of computing. Among them, the Ising machine is a non-von-Neumann solver that has received wide attention in recent years. It is capable of solving intractable combinatorial optimization (CO) problems, which are difficult to be solve using conventional digital computers. In fact, many CO problems can be mapped to finding the corresponding ground states of Ising model. At present, Ising machine prototypes based on different physical principles, such as emerging memristive oscillators, have been demonstrated, among which the Ising Hamiltonian solver based on the coupled oscillator network simultaneously holds the advantages of room-temperature operation, compact footprint, low power consumption, and fast speed to solution. This paper comprehensively surveys the recent developments in this important field, including the types of oscillators, the implementation principle of the Ising model, and the solver’s performance. Finally, methods to further improve the performance have also been suggested.
Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
Authors: Fobi Kwabena , Bunce Richard A.
Published: June 2022

The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl.
LncRNA MALAT1 Participates in Protection of High-Molecular-Weight Hyaluronan against Smoke-Induced Acute Lung Injury by Upregulation of SOCS-1
Authors: Li Shaoguang , Li Bin , Lang Ke , Gong Yubei , Cheng Xiang , Deng Shufen , Shi Qiwen , Zhao Hang
Published: June 2022

Smoke-induced acute lung injury (ALI) is a grievous disease with high mortality. Despite advances in medical intervention, no drug has yet been approved by the Food and Drug Administration (FDA) for ALI. In this study, we reported that pretreatment with high-molecular-weight hyaluronan (1600 kDa, HA1600) alleviated pulmonary inflammation and injury in mice exposed to smoke and also upregulated long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), as well as suppressor of cytokine signaling-1 (SOCS-1), in the lung tissues. Next, we overexpressed MALAT1 in the lungs by intratracheal administration of adenovirus cloned with MALAT1 cDNA and found that the survival of mice after smoke exposure was improved. Moreover, pulmonary overexpression of MALAT1 ameliorated smoke-induced ALI in mice and elevated the level of SOCS-1 in the lungs. In conclusion, the results pointed out that HA1600 exerted a protective effect against smoke-induced ALI through increasing the MALAT1 level and the subsequent SOCS-1 expression. Our study provides a potential therapeutic approach to smoke-induced ALI and a novel insight into the mechanism of action of HA1600.
Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS
Authors: Wang Taiyu , Yang Hailong , Yang Jie , Guo Ningjie , Wu Guodong , Xu Xueyu , An Ming
Published: June 2022

A novel method of ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of four potential genotoxic impurities (PGIs) in the active pharmaceutical ingredients of TSD-1, a novel P2Y12 receptor antagonist. Four PGIs were named, 4-nitrobenzenesulfonic acid, methyl 4-nitrobenzenesulfonate, ethyl 4-nitrobenzenesulfonate, and isopropyl 4-nitrobenzenesulfonate. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying four PGIs at 15.0 ppm in samples of 0.5 mg/mL concentration. This validated approach presented very low limits (0.1512–0.3897 ng/mL), excellent linearity (coefficients > 0.9900), and a satisfactory recovery range (94.9–115.5%). The method was sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity, and robustness and, thus, has high practicality in the pharmaceutical quality control of TSD-1.
Choline Chloride/Urea Deep Eutectic Solvents: A Promising Reaction Medium for the Synthesis of Bio-Based Poly(hydroxyurethane)s
Authors: Shen Guanfei , Andrioletti Bruno
Published: June 2022

The development of more sustainable and eco-friendly polymers has attracted much attention from researchers over the past decades. Among the different strategies that can be implemented towards this goal, the substitution of the toxic reagents/monomers often used in polyurethane chemistry has stimulated much innovation leading to the development of the hydroxylated version of PURs, namely, the poly(hydroxyurethane)s (PHURs). However, some PHURs remain far from being sustainable as their synthesis may involve monomers and/or solvents displaying poor environmental impacts. Herein, we report on the use of more sustainable conditions to synthesize the biobased polycarbonates involved in the aminolysis reaction. In addition, we demonstrate that the use of renewable deep eutectic solvents (DESs) can act both as excellent solvents and organocatalysts to promote the aminolysis reaction.
A Framework for Stakeholders’ Involvement in Digital Productions for Cultural Heritage Tourism
Authors: Calvi Licia , Weber-Sabil Jessika , Asmar Daniel , Socías Perez Xavi
Published: June 2022

This paper proposes a new framework for the production and development of immersive and playful technologies in cultural heritage in which different stakeholders such as users and local communities are involved early on in the product development chain. We believe that an early stage of co-creation in the design process produces a clear understanding of what users struggle with, facilitates the creation of community ownership and helps in better defining the design challenge at hand. We show that adopting such a framework has several direct and indirect benefits, including a deeper sense of site and product ownership as direct benefits to the individual, and the creation and growth of tangential economies to the community.
Self-Powered Resistance-Switching Properties of Pr0.7Ca0.3MnO3 Film Driven by Triboelectric Nanogenerator
Authors: Huang Yanzi , Wan Lingyu , Jiang Jiang , Li Liuyan , Zhai Junyi
Published: June 2022

As one of the promising non-volatile memories (NVMs), resistive random access memory (RRAM) has attracted extensive attention. Conventional RRAM is deeply dependent on external power to induce resistance-switching, which restricts its applications. In this work, we have developed a self-powered RRAM that consists of a Pr0.7Ca0.3MnO3 (PCMO) film and a triboelectric nanogenerator (TENG). With a traditional power supply, the resistance switch ratio achieves the highest switching ratio reported so far, 9 × 107. By converting the mechanical energy harvested by a TENG into electrical energy to power the PCMO film, we demonstrate self-powered resistance-switching induced by mechanical movement. The prepared PCMO shows excellent performance of resistance switching driven by the TENG, and the resistance switch ratio is up to 2 × 105, which is higher than the ones ever reported. In addition, it can monitor real-time mechanical changes and has a good response to the electrical signals of different waveforms. This self-powered resistance switching can be induced by random movements based on the TENG. It has potential applications in the fields of self-powered sensors and human-machine interaction.
Application of Micro/Nanoporous Fluoropolymers with Reduced Bioadhesion in Digital Microfluidics
Authors: Goralczyk Andreas , Bhagwat Sagar , Mayoussi Fadoua , Nekoonam Niloofar , Sachsenheimer Kai , Hou Peilong , Kotz-Helmer Frederik , Helmer Dorothea , Rapp Bastian E.
Published: June 2022

Digital microfluidics (DMF) is a versatile platform for conducting a variety of biological and chemical assays. The most commonly used set-up for the actuation of microliter droplets is electrowetting on dielectric (EWOD), where the liquid is moved by an electrostatic force on a dielectric layer. Superhydrophobic materials are promising materials for dielectric layers, especially since the minimum contact between droplet and surface is key for low adhesion of biomolecules, as it causes droplet pinning and cross contamination. However, superhydrophobic surfaces show limitations, such as full wetting transition between Cassie and Wenzel under applied voltage, expensive and complex fabrication and difficult integration into already existing devices. Here we present Fluoropor, a superhydrophobic fluorinated polymer foam with pores on the micro/nanoscale as a dielectric layer in DMF. Fluoropor shows stable wetting properties with no significant changes in the wetting behavior, or full wetting transition, until potentials of 400 V. Furthermore, Fluoropor shows low attachment of biomolecules to the surface upon droplet movement. Due to its simple fabrication process, its resistance to adhesion of biomolecules and the fact it is capable of being integrated and exchanged as thin films into commercial DMF devices, Fluoropor is a promising material for wide application in DMF.
Deformation of Copper Nanowire under Coupled Tension–Torsion Loading
Authors: Lu Hongquan , Dong Bin , Zhang Junqian , Lü Chaofeng , Zhan Haifei
Published: June 2022

Metallic nanowires (NWs) are essential building blocks for flexible electronics, and experience different deformation modes due to external mechanical loading. Using atomistic simulations, this work investigated the deformation behavior of copper nanowire under coupled tension–torsion loading. A transition in both yielding pattern and dislocation pattern were observed with varying torsion/tension strain ratios. Specifically, increasing the torsion/tension strain ratio (with larger torsional strain) triggered the nucleation of different partial dislocations in the slip system. At low torsion/tension strain ratios, plastic deformation of the nanowire was dominated by stacking faults with trailing partial dislocations pinned at the surface, shifting to two partial dislocations with stacking faults as the strain ratio increases. More interestingly, the NW under tension-dominated loading exhibited a stacking fault structure after yielding, whereas torsion-dominated loading resulted in a three-dimensional dislocation network within the structure. This work thus suggests that the deformation behavior of the NW varies depending on the coupled mechanical loading, which could be beneficial for various engineering applications.
Successful Consolidation/Maintenance Therapy with Single Agent Ibrutinib for Primary CNS Lymphoma after Initial Induction Therapy
Authors: Du Steven , Bota Daniela , Kong Xiao-Tang
Published: June 2022

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease that originates from lymphocytes and develops in the central nervous system. There is no standard consolidation/maintenance therapy for PCNSL. While there exists a variety of options, the high chance of inferior outcomes for elderly patients and the risk of neurotoxicity requires exploration of alternative options for consolidation/maintenance therapy for PCNSL in the elderly population with CNS lymphoma. We treated one 77-year-old patient with single agent ibrutinib, a Bruton’s tyrosine kinase inhibitor that crosses the blood-brain-barrier, as consolidation/maintenance therapy after induction therapy with high-dose methotrexate (HD-MTX) and rituximab plus temozolomide. This treatment resulted in good tolerance, further resolution of a small residue lymphoma, and sustained remission. The patient has completed one year of consolidation/maintenance therapy and is currently under clinical and imaging surveillance. She has survived 27 months without recurrence since diagnosis. This case shows the potential effectiveness of single agent ibrutinib as consolidation/maintenance therapy for PCNSL after induction therapy. More cases are needed to confirm the findings.
Comment on Brinkis et al. Nutrient Intake with Early Progressive Enteral Feeding and Growth of Very Low-Birth-Weight Newborns. Nutrients 2022, 14, 1181
Authors: Manzar Shabih
Published: June 2022

I read with great interest the article by Brinkis et al [...]
Dietary Plant Sterols and Phytosterol-Enriched Margarines and Their Relationship with Cardiovascular Disease among Polish Men and Women: The WOBASZ II Cross-Sectional Study
Authors: Witkowska Anna Maria , Waśkiewicz Anna , Zujko Małgorzata Elżbieta , Cicha-Mikołajczyk Alicja , Mirończuk-Chodakowska Iwona , Drygas Wojciech
Published: June 2022

Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD). Phytosterols, present in food or phytosterol-enriched products, can reduce cholesterol available for absorption. The present study aimed to investigate the association between habitual intake of total and individual plant sterols (β-sitosterol, campesterol, and stigmasterol) or a diet combined with phytosterol-enriched products and CVD in a cross-section of Polish adults, participants of the Multicenter National Health Survey II (WOBASZ II). Among men (n = 2554), median intakes of plant sterols in terciles ranged between 183–456 mg/d and among women (n = 3136), 146–350 mg/d in terciles. The intake of phytosterols, when consumed with food containing phytosterols, including margarine, ranged between 184–459 mg/d for men and 147–352 mg/d for women. Among both men and women, beta-sitosterol intake predominated. Plant sterol intake was lower among both men and women with CVD (p = 0.016) compared to those without CVD. Diet quality, as measured by the Healthy Diet Index (HDI), was significantly higher in the third tercile of plant sterol intake for both men and women and the entire study group (p < 0.0001). This study suggests that habitual dietary intake of plant sterols may be associated with a lower chance of developing CVD, particularly in men.
Mushrooms as a Resource for Mibyou-Care Functional Food; The Role of Basidiomycetes-X (Shirayukidake) and Its Major Components
Authors: Matsugo Seiichi , Sakamoto Toshio , Wakame Koji , Nakamura Yutaka , Watanabe Kenichi , Konishi Tetsuya
Published: June 2022

Mibyou has been defined in traditional oriental medicine as a certain physiological condition whereby an individual is not ill but not healthy; it is also often referred to as a sub-healthy condition. In a society focused on longevity, “Mibyou-care” becomes of primary importance for healthy lifespan expenditure. Functional foods can play crucial roles in Mibyou-care; thus, the search for novel resources of functional food is an important and attractive research field. Mushrooms are the target of such studies because of their wide variety of biological functions, such as immune modulation and anti-obesity and anticancer activities, in addition to their nutritional importance. Basidiomycetes-X (BDM-X; Shirayukidake in Japanese) is a mushroom which has several attractive beneficial health functions. A metabolome analysis revealed more than 470 components of both nutritional and functional interest in BDM-X. Further isolation and purification studies on its components using radical scavenging activity and UV absorbance identified ergosterol, (10E,12Z)-octadeca-10,12-dienoic acid (CLA), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), formyl pyrrole analogues (FPA), including 4-[2-foemyl-5-(hydroxymethyl)-1H-pyrrole-1-yl] butanamide (FPAII), adenosine and uridine as major components. Biological activities attributed to these components were related to the observed biological functions of BDM-X, which suggest that this novel mushroom is a useful resource for Mibyou-care functional foods and medicines.
Interrelation between Stress Management and Secretion Systems of Ralstonia solanacearum: An In Silico Assessment
Authors: Banerjee Goutam , Quan Fu-Shi , Mondal Amit , Sur Shantanu , Banerjee Pratik , Chattopadhyay Pritam
Published: June 2022

Ralstonia solanacearum (Rs), the causative agent of devastating wilt disease in several major and minor economic crops, is considered one of the most destructive bacterial plant pathogens. However, the mechanism(s) by which Rs counteracts host-associated environmental stress is still not clearly elucidated. To investigate possible stress management mechanisms, orthologs of stress-responsive genes in the Rs genome were searched using a reference set of known genes. The genome BLAST approach was used to find the distributions of these orthologs within different Rs strains. BLAST results were first confirmed from the KEGG Genome database and then reconfirmed at the protein level from the UniProt database. The distribution pattern of these stress-responsive factors was explored through multivariate analysis and STRING analysis. STRING analysis of stress-responsive genes in connection with different secretion systems of Rs was also performed. Initially, a total of 28 stress-responsive genes of Rs were confirmed in this study. STRING analysis revealed an additional 7 stress-responsive factors of Rs, leading to the discovery of a total of 35 stress-responsive genes. The segregation pattern of these 35 genes across 110 Rs genomes was found to be almost homogeneous. Increasing interactions of Rs stress factors were observed in six distinct clusters, suggesting six different types of stress responses: membrane stress response (MSR), osmotic stress response (OSR), oxidative stress response (OxSR), nitrosative stress response (NxSR), and DNA damage stress response (DdSR). Moreover, a strong network of these stress responses was observed with type 3 secretion system (T3SS), general secretory proteins (GSPs), and different types of pili (T4P, Tad, and Tat). To the best of our knowledge, this is the first report on overall stress response management by Rs and the potential connection with secretion systems.
Immunodominant B-Cell Linear Epitope on the VP1 P Domain of a Feline Norovirus Cat Model
Authors: Takano Tomomi , Ryu Mizuki , Doki Tomoyoshi , Kusuhara Hajime
Published: June 2022

Norovirus (NoV) infection remains a major public health concern worldwide. Appropriate animal models are essential for the development of effective NoV vaccines. We previously established the feline NoV (FNoV)-cat model as a surrogate animal model for human NoV infection. In the present study, we analyzed the B-cell linear epitope in the P domain of FNoV to confirm the basic immunological features of the FNoV-cat model. B-cell linear epitopes were present in the P2 subdomain. We compared antibody levels to peptides containing the B-cell linear epitope (P-10) in three FNoV-infected cats with time-course changes in viral load and symptom scoring. After FNoV infection, viral shedding and clinical symptoms were shown to improve by elevated levels of antibodies against P-10 in the plasma. This report provides important information for understanding NoV infections in humans and cats.
Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict PET Image Quality of Three Generations EGFR TKI in Advanced-Stage NSCLC Patients
Authors: Bartelink I. , van de Stadt E. , Leeuwerik A. , Thijssen V. , Hupsel J. , van den Nieuwendijk J. , Bahce I. , Yaqub M. , Hendrikse N.
Published: June 2022

Introduction: Epidermal growth factor receptor (EGFR) mutated NSCLC is best treated using an EGFR tyrosine kinase inhibitor (TKI). The presence and accessibility of EGFR overexpression and mutation in NSCLC can be determined using radiolabeled EGFR TKI PET/CT. However, recent research has shown a significant difference between image qualities (i.e., tumor-to-lung contrast) in three generation EGFR TKIs: 11C-erlotinib, 18F-afatinib and 11C-osimertinib. In this research we aim to develop a physiological pharmacokinetic (PBPK)-model to predict tumor-to-lung contrast and as a secondary outcome the uptake of healthy tissue of the three tracers. Methods: Relevant physicochemical and drug specific properties (e.g., pKa, lipophilicity, target binding) for each TKI were collected and applied in established base PBPK models. Key hallmarks of NSCLC include: immune tumor deprivation, unaltered tumor perfusion and an acidic tumor environment. Model accuracy was demonstrated by calculating the prediction error (PE) between predicted tissue-to-blood ratios (TBR) and measured PET-image-derived TBR. Sensitivity analysis was performed by excluding each key component and comparing the PE with the final mechanistical PBPK model predictions. Results: The developed PBPK models were able to predict tumor-to-lung contrast for all EGFR-TKIs within threefold of observed PET image ratios (PE tumor-to-lung ratio of −90%, +44% and −6.3% for erlotinib, afatinib and osimertinib, respectively). Furthermore, the models depicted agreeable whole-body distribution, showing high tissue distribution for osimertinib and afatinib and low tissue distribution at high blood concentrations for erlotinib (mean PE, of −10.5%, range −158%–+190%, for all tissues). Conclusion: The developed PBPK models adequately predicted the image quality of afatinib and osimertinib and erlotinib. Some deviations in predicted whole-body TBR lead to new hypotheses, such as increased affinity for mutated EGFR and active influx transport (erlotinib into excreting tissues) or active efflux (afatinib from brain), which is currently unaccounted for. In the future, PBPK models may be used to predict the image quality of new tracers.
Anti-Cytomegalovirus Therapy: Whether and When to Initiate, Those Are the Questions
Authors: Aoyama Yumi , Sugiyama Seiko , Yamamoto Takenobu
Published: June 2022

Cytomegalovirus (CMV) reactivation in patients with autoimmune bullous disease (AIBD) or severe drug eruption treated with immunosuppressive therapy was traditionally thought to be merely an epiphenomenon of the underlying immunosuppression. However, a detailed review of the clinical course of these patients revealed that CMV reactivation occurs upon rapid immune recovery, which is termed immune reconstitution inflammatory syndrome (IRIS), and that the timely initiation of anti-CMV therapy, when combined with maintenance doses of immunosuppressive agents, contributes to a rapid resolution of severe infectious complications thought to be refractory to conventional immunosuppressive therapies and unrelated to CMV reactivation. Thus, CMV reactivation resulting in fatal outcomes (CMV-IRIS) can be prevented by the timely detection of CMV DNA or antigens in the blood and by rapidly starting anti-CMV therapy while maintaining immunosuppressive therapy. Anti-CMV therapy is highly recommended for patients with CMV-IRIS or severe drug eruption who have risk factors for CMV reactivation resulting in fatal outcomes.
A Role for Neuropeptide S in Alcohol and Cocaine Seeking
Authors: Cannella Nazzareno , Borruto Anna Maria , Petrella Michele , Micioni Di Bonaventura Maria Vittoria , Soverchia Laura , Cifani Carlo , De Carlo Sara , Domi Esi , Ubaldi Massimo
Published: June 2022

The neuropeptide S (NPS) is the endogenous ligand of the NPS receptor (NPSR). The NPSR is widely expressed in brain regions that process emotional and affective behavior. NPS possesses a unique physio-pharmacological profile, being anxiolytic and promoting arousal at the same time. Intracerebroventricular NPS decreased alcohol consumption in alcohol-preferring rats with no effect in non-preferring control animals. This outcome is most probably linked to the anxiolytic properties of NPS, since alcohol preference is often associated with high levels of basal anxiety and intense stress-reactivity. In addition, NPSR mRNA was overexpressed during ethanol withdrawal and the anxiolytic-like effects of NPS were increased in rodents with a history of alcohol dependence. In line with these preclinical findings, a polymorphism of the NPSR gene was associated with anxiety traits contributing to alcohol use disorders in humans. NPS also potentiated the reinstatement of cocaine and ethanol seeking induced by drug-paired environmental stimuli and the blockade of NPSR reduced reinstatement of cocaine-seeking. Altogether, the work conducted so far indicates the NPS/NPSR system as a potential target to develop new treatments for alcohol and cocaine abuse. An NPSR agonist would be indicated to help individuals to quit alcohol consumption and to alleviate withdrawal syndrome, while NPSR antagonists would be indicated to prevent relapse to alcohol- and cocaine-seeking behavior.
Preclinical Drug Pharmacokinetic, Tissue Distribution and Excretion Profiles of the Novel Limonin Derivate HY-071085 as an Anti-Inflammatory and Analgesic Candidate in Rats and Beagle Dogs
Authors: Dong Liping , Liu Wenjuan , Zhao Xiaoyuan , Yu Feng , Xu Yungen , Su Mengxiang
Published: June 2022

Limonin is one of the research hotspots in natural drug development. However, its low solubility in water leads to poor oral bioavailability, discouraging the further study of its potential as a candidate compound. In order to overcome this limitation, and to enhance its biological activities, a novel limonin derivative—HY-071085—was synthesized by structural modification, and has exhibited strong anti-inflammatory and analgesic activity. In order to achieve a thorough understanding of the biological actions of HY-071085 in vivo, this study evaluated the pharmacokinetics and bioavailability of HY-071085 in rats and beagle dogs, and the distribution and excretion in rats. Using ultra-high-performance liquid chromatography-tandem mass spectrometry, the kinetic profiles of HY-071085 in the plasma of healthy rats and beagle dogs after a single gavage, repeated gavages and the intravenous injection of HY-071085 were studied. The tissue distribution (heart, liver, spleen, lung, kidney, gastric tissue, intestine, brain, skin, testis, ovary and womb) and excretion of HY-071085 were also studied. These results showed that HY-071085 has nonlinear dynamic characteristics in rat and beagle dog plasma. It was found that the plasma concentrations of HY-071085 in female rats were significantly higher than those in male rats after a single oral administration. There were gender differences in the kinetic behavior of HY-071085 in rats; however, there was no difference identified in dogs. HY-071085 was mainly eliminated as metabolites in rats, and was distributed in most of the tissues except the brain, with the highest content being in the gastric tissue and intestinal arease, followed by the liver, spleen, fat, lung, kidney, ovary and heart. The bioavailability of HY-071085 in male and female rats was 2.8% and 10.8%, respectively, and was about 13.1% in beagle dogs. The plasma protein binding rate of HY-071085 in rats, beagle dogs and humans ranged from 32.9% to 100%, with obvious species differences. In conclusion, our study provides useful information regarding the absorption, distribution and excretion of HY-071085, which will provide a good base for the study of the mechanism of its biological effects.
Photoprotective Agents Obtained from Aromatic Plants Grown in Colombia: Total Phenolic Content, Antioxidant Activity, and Assessment of Cytotoxic Potential in Cancer Cell Lines of Cymbopogon flexuosus L. and Tagetes lucida Cav. Essential Oils
Authors: Caballero-Gallardo Karina , Quintero-Rincón Patricia , Stashenko Elena E. , Olivero-Verbel Jesus
Published: June 2022

Photoprotective agents obtained from plants provide benefits for the health of the skin. The present study aims to assess the total phenolic content (TPC) and in vitro UV-protective properties of twelve essential oils (EOs) from plants grown in Colombia and to evaluate the antioxidant and cytotoxic potential of two species identified as photoprotective potentials: Cymbopogon flexuosus and Tagetes lucida. The composition of EOs was studied by GC/MS. The cytotoxicity of both EOs was examined using an MTT assay, and an H2-DCFDA probe was employed to estimate the intracellular production of ROS in HepG2 and Calu-1 cells. Major constituents (≥10%) were neral, geranial, geranyl acetate in C. flexuosus and estragole in T. lucida. The TPC for C. flexuosus and T. lucida EOs were ≥10 mg GAE/g of byproduct. Both EOs showed photoprotective properties (SPFin vitro: 13–14), and long-wavelength UVA protection (λc > 370 nm). HepG2 and Calu-1 cells exposed to C. flexuosus exhibited antiproliferative activity (˂50%) at 125 µg/mL, while T. lucida was at 250 and 500 µg/mL. The IC50 values for C. flexuosus were 75 and 100 µg/mL in HepG2 and Calu-1 cells, respectively, whereas those for T. lucida were >250 µg/mL. These EOs achieved significant inhibitory effects (between 15.6 and 40.4%) against H2O2-induced oxidative stress. The results showed that EO compounds recognized as antioxidants could counteract the effects elicited by H2O2.
Phylogeny and Taxonomic Synopsis of the Genus Bougainvillea (Nyctaginaceae)
Authors: Bautista Mary Ann C. , Zheng Yan , Boufford David E. , Hu Zhangli , Deng Yunfei , Chen Tao
Published: June 2022

Bougainvillea Comm. ex Juss. is one of the renowned genera in the Nyctaginaceae, but despite its recognized horticultural value, the taxonomy and phylogeny of the genus is not well-studied. Phylogenetic reconstructions based on plastid genomes showed that B. pachyphylla and B. peruviana are basal taxa, while B. spinosa is sister to two distinct clades: the predominantly cultivated Bougainvillea clade (B. spectabilis, B. glabra, B. arborea, B. cultivar, B. praecox) and the clade containing wild species of Bougainvillea (B. berberidifolia, B. campanulata, B. infesta, B. modesta, B. luteoalba, B. stipitata, and B. stipitata var. grisebachiana). Early divergence of B. peruviana, B. pachyphylla and B. spinosa is highly supported, thus the previously proposed division of Bougainvillea into two subgenera (Bougainvillea and Tricycla) was not reflected in this study. Morphological analysis also revealed that leaf arrangement, size, and indumentum together with the perianth tube and anthocarp shape and indumentum are important characteristics in differentiating the species of Bougainvillea. In the present study, 11 species and one variety are recognized in Bougainvillea. Six names are newly reduced to synonymy, and lectotypes are designated for 27 names. In addition, a revised identification key and illustrations of the distinguishing parts are also provided in the paper.