bluuebunny/crossref_metadata_2025 huggingface dataset:
The Residual Spaces of Developmental Urbanism as Opportunity for Green Cities and Improvement of Human Wellbeing
Authors: Latasa Itxaro , Laurenz Angela
Published: March 2023

City densification and greening are two priority urban-policy objectives, for the coming years, aimed at making cities more resilient to climate change, slowing the spread of urbanization and improving the quality of life in cities. These are sometimes contradictory objectives that require fine and deep analysis to create approaches and methods that combine them. The most recent research has presented so-called small urban green spaces (SUGSs) as a viable alternative to achieve this double objective. This was the starting point of this research, which used GIS digital analysis and microscale fieldwork to study the possibilities of greening an excessively dense and low-quality urban space in the city of Pamplona (Spain). The results thereof showed that the urban structure of this neighbourhood contains a large number of small spaces with no specific use or function—residual, surface and vertical spaces—and that are simply undefined remnants between buildings and streets, or party walls that were never built. Only these surface spaces occupy a total area that is twice the size of the existing green spaces. Based on these results, this work explores the possibility of increasing the green areas of the neighbourhood through new SUGSs and the creation of a green corridor that increases environmental and social connectivity and the quality of life in the studied space.
Crocus sativus Extract as a Biological Agent for Disease-Modifying Therapy of Collagenase-Induced Mouse Model of Osteoarthritis
Authors: Boneva Blagovesta , Marchev Andrey , Amirova Kristiana , Ganova Petya , Georgiev Milen , Tchorbanov Andrey , Mihaylova Nikolina
Published: March 2023

Objectives: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to be common to all forms of the disease. Currently used therapies for control of the disease are mainly nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid medications. The aim of this study was to investigate the extract from Crocus sativus as a biological disease-suppressing therapy agent. Methods: Balb/c mice were injected intra-articularly with Clostridium histolyticum type IA for induction of osteoarthritis. The mice were randomized to five groups: control group, I group (CIOA untreated), II group (CIOA + 100 mg/kg/daily saffron), III group (CIOA + 50 mg/kg/daily saffron), IV group (CIOA + 25 mg/kg/daily saffron). Flow-cytometry analysis was used to study the splenocytes’ phenotype isolated from the treated animals. The serum levels of inflammatory and anti-inflammatory cytokines were analyzed with ELISA. The histological assessment was used to analyze the saffron extract effect on histopathological alterations. Results: Saffron treatment significantly decreased osteoarthritis-associated joint histological manifestations and decreased serum TNFα levels. The flow-cytometry analysis showed a decrease in pro-inflammatory immune cell subtypes in the spleen. Conclusions: The results obtained suggest that saffron affected the disease progression and could be a potential therapeutic approach in osteoarthritic patients’ therapy.
The Bacterial Nucleoid: From Electron Microscopy to Polymer Physics—A Personal Recollection
Authors: Woldringh Conrad L.
Published: March 2023

In the 1960s, electron microscopy did not provide a clear answer regarding the compact or dispersed organization of the bacterial nucleoid. This was due to the necessary preparation steps of fixation and dehydration (for embedding) and freezing (for freeze-fracturing). Nevertheless, it was possible to measure the lengths of nucleoids in thin sections of slow-growing Escherichia coli cells, showing their gradual increase along with cell elongation. Later, through application of the so-called agar filtration method for electron microscopy, we were able to perform accurate measurements of cell size and shape. The introduction of confocal and fluorescence light microscopy enabled measurements of size and position of the bacterial nucleoid in living cells, inducing the concepts of “nucleoid occlusion” for localizing cell division and of “transertion” for the final step of nucleoid segregation. The question of why the DNA does not spread throughout the cytoplasm was approached by applying polymer-physical concepts of interactions between DNA and proteins. This gave a mechanistic insight in the depletion of proteins from the nucleoid, in accordance with its low refractive index observed by phase-contrast microscopy. Although in most bacterial species, the widely conserved proteins of the ParABS-system play a role in directing the segregation of newly replicated DNA strands, the basis for the separation and opposing movement of the chromosome arms was proposed to lie in preventing intermingling of nascent daughter strands already in the early replication bubble. E. coli, lacking the ParABS system, may be suitable for investigating this basic mechanism of DNA strand separation and segregation.
3-Cyclohexyl-6-phenyl-1-(p-tolyl)pyrimidine-2,4(1H,3H)-dione
Authors: Messa Francesco , Perrone Serena , Salomone Antonio
Published: March 2023

The synthesis of a novel uracil derivative, 3-cyclohexyl-6-phenyl-1-(p-tolyl)pyrimidine-2,4(1H,3H)-dione (4), is reported via a four-component reaction involving an α-chloroketone (1), an aliphatic isocyanate (2), a primary aromatic amine (3) and carbon monoxide. The proposed reaction mechanism involves a Pd-catalyzed carbonylation of 2-chloro-1-phenylethan-1-one (1), leading to a β-ketoacylpalladium key intermediate, and, at the same time, in situ formation of non-symmetrical urea deriving from cyclohexyl isocyanate (2) and p-toluidine (3). After a chemo-selective acylation of the non-symmetrical urea and the subsequent cyclization of the acylated intermediate, 3-cyclohexyl-6-phenyl-1-(p-tolyl)pyrimidine-2,4(1H,3H)-dione (4) is formed. Uracil derivative 4 was isolated in good yield (73%) and fully characterized by 1H, 13C, 2D 1H-13C HSQC and 2D 1H-13C HMBC NMR, FT-IR spectroscopy and GC-MS spectrometry.
High-Cycle Fatigue Behaviour of the Aluminium Alloy 5083-H111
Authors: Nečemer Branko , Zupanič Franc , Vuherer Tomaž , Glodež Srečko
Published: March 2023

This study presents a comprehensive experimental investigation of the high-cycle fatigue (HCF) behaviour of the ductile aluminium alloy AA 5083-H111. The analysed specimens were fabricated in the rolling direction (RD) and transverse direction (TD). The HCF tests were performed in a load control (load ratio R = 0.1) at different loading levels under the loading frequency of 66 Hz up to the final failure of the specimen. The experimental results have shown that the S–N curves of the analysed Al-alloy consist of two linear curves with different slopes. Furthermore, RD-specimens demonstrated longer fatigue life if compared to TD-specimens. This difference was about 25% at the amplitude stress 65 MPa, where the average fatigue lives 276,551 cycles for RD-specimens, and 206,727 cycles for TD-specimens were obtained. Similar behaviour was also found for the lower amplitude stresses and fatigue lives between 106 and 108 cycles. The difference can be caused by large Al6(Mn,Fe) particles which are elongated in the rolling direction and cause higher stress concentrations in the case of TD-specimens. The micrography of the fractured surfaces has shown that the fracture characteristics were typical for the ductile materials and were similar for both specimen orientations.
Mg2+ and Cu2+ Charging Agents Improving Electrophoretic Deposition Efficiency and Coating Adhesion of Nano-TbF3 on Sintered Nd-Fe-B Magnets
Authors: Zhang Weitao , Luo Yang , Sun Xiaojun , Zhang Ze , Peng Haijun , Yang Yuanfei , Yan Wenlong , Wang Zilong , Yu Dunbo
Published: March 2023

In order to prepare nano-TbF3 coating with high quality on the surface of Nd-Fe-B magnets by electrophoretic deposition (EPD) more efficiently, Mg2+ and Cu2+ charging agents are introduced into the electrophoretic suspension and the influence on the electrophoretic deposition is systematically investigated. The results show that the addition of Mg2+ and Cu2+ charging agents can improve the electrophoretic deposition efficiency and coating adhesion of nano-TbF3 powders on sintered Nd-Fe-B magnets. The EPD efficiency increases by 116% with a relative content of Mg2+ as 3%, while it increases by 109% with a relative content of Cu2+ as 5%. Combining the Hamaker equation and diffusion electric double layer theory, the addition of Mg2+ and Cu2+ can change the zeta potential of charged particles, resulting in the improvement of EPD efficiency. The relative content of Mg2+ below 3% and Cu2+ below 5% can increase the thickness of the diffusion electric double layer, the excessive addition of a charging agent will compress the diffusion electric double layer, and thicker diffusion layer represents higher zeta potential. Furthermore, the addition of Mg2+ and Cu2+ charging agents greatly improves the coating adhesion, and the critical load for the cracking of the coating increases to 146.4 mN and 40.2 mN from 17.9 mN, respectively.
Synthesis of Natural-Inspired Materials by Irradiation: Data Mining from the Perspective of Their Functional Properties in Wastewater Treatment
Authors: Braşoveanu Mirela , Sabbaghi Hassan , Nemţanu Monica R.
Published: March 2023

The present study is focused on assessing the interrelation of variables involved in the synthesis of natural-inspired copolymers by electron beam grafting while taking the functionality of the resulting materials into account. In this respect, copolymers of starch-graft-polyacrylamide (St-g-PAM) were synthesized by irradiation, and their flocculation efficiency regarding the total suspended solids (TSS), chemical oxygen demand (COD), and fatty matters (FM) was tested in coagulation–flocculation experiments at laboratory scale on wastewater from the oil industry. Data mining involved approaches related to the association (correlation and dimensionality reduction with principal component analysis (PCA)), clustering by agglomerative hierarchical clustering (AHC), classifying by classification and regression tree (CART), and prediction (decision tree prediction, multiple linear regression (MLR), and principal component regression (PCR)) of treatments applied with the variation of the monomer concentration, irradiation dose, and dose rate. The relationship mining proved that the level of COD was significantly affected by the irradiation dose and monomer concentration, and FM was mainly affected by the dose rate (significance level = 0.05). TSS showed the highest negative correlation with the tested variables. Moreover, the consequences of MLR demonstrated an acceptable accuracy (mean absolute percentage error < 5%) for COD and FM; meanwhile, linear modeling together with the consequences of PCA in the structure of PCR could help to simplify and improve the prediction accuracy of equations.
Multiscale Study of the Effect of Fiber Twist Angle and Interface on the Viscoelasticity of 2D Woven Composites
Authors: Li Beibei , Liu Cheng , Zhao Xiaoyu , Ye Jinrui , Guo Fei
Published: March 2023

Time and temperature affect the viscoelasticity of woven composites, and thus affect their long-term mechanical properties. We develop a multiscale method considering fiber twist angle and interfaces to predict viscoelasticity. The multiscale approach is based on homogenization theory and the time–temperature superposition principle (TTSP). It is carried out in two steps. Firstly, the effective viscoelasticity properties of yarn are calculated using microscale homogenization; yarn comprises elastic fibers, interface, and a viscoelastic matrix. Subsequently, the effective viscoelasticity properties of woven composites are computed by mesoscale homogenization; it consists of homogenized viscoelastic yarns and matrix. Moreover, the multiscale method is verified using the Mechanics of Structure genome (MSG) consequence. Finally, the effect of temperature, fiber twist angle, fiber array, and coating on either the yarn’s effective relaxation stiffness or the relaxation moduli of the woven composite is investigated. The results show that increased temperature shortens the relaxation time of viscoelastic woven composites, and fiber twist angle affects tensors in the relaxation stiffness matrix of the yarn; the coating affects the overall mechanical properties of woven composites as well.
Modification of Poly(vinyl chloride) with Bio-Based Cassia Oil to Improve Thermo-Mechanical and Antimicrobial Properties
Authors: Skórczewska Katarzyna , Szulc Joanna , Lewandowski Krzysztof , Ligocka Anna , Wilczewski Sławomir
Published: March 2023

The purpose of this study was to modify plasticised PVC to obtain a material with antimicrobial properties and selected mechanical properties. Natural cassia oil (CO) was used to modify plasticised PVC materials. The modified material was produced by extrusion. The introduced modifier had a maximum concentration of 20 phr. Rheological and mechanical properties were evaluated, and the glass transition temperature was determined. The antioxidant and antimicrobial activity of the agar diffusion method was investigated by analysing the growth inhibition zones against Enterococcus faecalis and Listeria monocytogenes. A favourable effect of the cassia oil content on the increase in antioxidant activity of the developed polymeric materials was found with an increase in the modifier content and the duration of action (30 days). The largest growth restriction zones were observed for L. monocytogenes, i.e., they showed the highest sensitivity to the modified material. The simultaneous decrease in modulus of elasticity, increase in elongation at break, and decrease in Tg indicate that the modifier has a plasticising effect on PVC. The developed material may find application as an active and/or functional material, especially as an emitter of antimicrobial agents, in the packaging used to store minimally processed food.
Conical Grinding Wheel Ultrasonic-Assisted Grinding Micro-Texture Surface Formation Mechanism
Authors: Han Jiaying , Jiang Yiqi , Li Xinrui , Li Qing
Published: March 2023

The rotating ultrasonic-assisted grinding (RUAG) experiment of the conical grinding wheel generated the intermittent pit-shaped micro-texture on the surface of the workpiece, reducing thermal damage and improving the lubrication characteristics compared with conventional grinding (CG). To further optimize the surface properties, this paper studied the formation mechanism of micro-texture. This study used as basis the theory that micro-debris volume equals the macroscopic material removal one to establish the mathematical equation of grinding depth. Thereafter, formulas of micro-texture feature parameters, including pit length, pit depth, and texture spacing were deduced. The solved microscopic grinding depth was alternatingly positive and negative, indicating that the alternating separation between the grinding grain and workpiece caused intermittent pits in the grinding. Through response surface analysis (RSA), this paper analyzed the relationships among macroscopic grinding depth, micro-texture feature parameters, and machining parameters (i.e., amplitude, feed rate, and rotational speed). Single-factor experiments of machining parameters, with finite element simulation and experiment methods, were performed to verify the theoretical micro-texture features. The simulated program formed three-dimensional surfaces with micro-textures. Their measurement results were consistent with the theoretical ones. Experimental results proved that the range of pit length covers the theoretical ones, further verifying the accuracy of the grinding depth model. For this grinding wheel, the 8–10 μm amplitude was optimal for better roughness, lubrication, and thermal damage. Roughness was improved when increasing the rotational speed or reducing the feed rate based on the experiment. If the rotational speed and feed rate exceed the limiting values, then continuous grinding will break down the abrasive grains and even damage the cubic boron nitride (CBN) coating. Experimental results likewise showed that the pit shape was closely related to the surface properties, which deserves further investigation.
Modeling of the Magnetic Turbulence Level and Source Function of Particle Injection from Multiple SEP Events
Authors: Lian Lele , Qin Gang , Wu Shuangshuang , Wang Yang , Cui Shuwang
Published: March 2023

Solar energetic particles (SEPs) are produced by solar eruptions and are harmful to spacecraft and astronauts. The four source function parameters of particle injection for SEP events and the magnetic turbulence level can be collectively referred to as key parameters. We reproduce the electron intensity-time profiles with simulations for five SEP events observed by multispacecraft such as ACE, STEREO-A, and STEREO-B, so we can obtain the five fitted key parameters for each of the events. We analyze the relationship among the five fitted key parameters, and also the relationship between these parameters and the observed event features. Thus, the model of key parameters are established. Next, we simulate another 12 SEP events with the key parameters model. Though the predicted electron intensity-time profiles do not fit the observed ones well, the peak flux and event-integrated fluence can be predicted accurately. Therefore, the model can be used to estimate the radiation hazards.
A Mathematical Tool to Investigate the Stability Analysis of Structured Uncertain Dynamical Systems with M-Matrices
Authors: Rehman Mutti-Ur , Alzabut Jehad , Fatima Nahid , Khan Sajid
Published: March 2023

The μ-value or structured singular value is a prominent mathematical tool to analyze and synthesize both the robustness and performance of time-invariant systems. We establish and analyze new results concerning structured singular values for the Hadamard product of real square M-matrices. The new results are obtained for structured singular values while considering a set of block diagonal uncertainties. The targeted uncertainties are of two types, that is, pure real scalar block uncertainties and real full-block uncertainties. The eigenvalue perturbation result is utilized in order to determine the behavior of the spectrum of perturbed matrices (A∘B)Δ(t) and ((A∘B)TΔ(t)+Δ(t)(A∘B)).
Microelongated Thermo-Elastodiffusive Waves of Excited Semiconductor Material under Laser Pulses Impact
Authors: Tayel Ismail M. , Lotfy Kh. , El-Bary Alaa A. , Alebraheem Jawdat , Mohammed Mogtaba A. Y.
Published: March 2023

The current study focuses on one-dimensional (1D) deformation in an excited microelongated semiconductor medium impacted by optoelectronics with exponential laser-pulsed heat. Diffusion effect is considered in a photothermal problem of a semiconducting media. Microelongated optoelectronics and a broad variety of concepts have been introduced. Appropriate solutions to a set of microelongated photothermal diffusion differential equations have been found. The homogeneous (thermal and mechanical) and isotropic characteristics of the medium are thought to be in the x-direction, including coupled diffusion equations. The linear photo-thermoelasticity (PTE) theory of semiconductors is used to describe thermo-elastodiffusive waves. As a case study, the developed theoretical framework may be used to explore the microelongation-photo-thermoelastic problem in a semiconductor medium caused by the laser pulse. The analytical linear solutions for the main quantities during thermoelastic (TD) and electronic (ED) deformation are obtained using Laplace transforms for dimensionless quantities. To obtain exact expressions of the important physical variables according to certain boundary surface conditions, numerical approximations solutions of the fundamental relevant relations are performed in the Laplace inverse time domain. To describe the wave propagation of the physical fields graphically, the computational results for silicon (Si) semiconductor material are derived using several cases of thermal memory and microelongation factors.
Random Forest and Whale Optimization Algorithm to Predict the Invalidation Risk of Backfilling Pipeline
Authors: Liu Weijun , Liu Zhixiang , Liu Zida , Xiong Shuai , Zhang Shuangxia
Published: March 2023

The problem of backfilling pipeline invalidation has become a bottleneck restricting the application and development of backfilling technology. This study applied the whale optimization algorithm and random forest (WOA–RF) to predict the invalidation risk of backfilling pipelines based on 59 datasets from actual mines. Eight influencing factors of backfilling pipeline invalidation risk were chosen as the input parameters of the WOA–RF model, and the risk level was selected as the output parameters of the WOA–RF model. Furthermore, random forest, decision tree, artificial neural network, k-nearest neighbor, and support vector machine models were also established according to the collected datasets. The prediction performance of the six classification models was compared. The evaluated results showed that the established WOA–RF hybrid model has the best prediction performance and the highest accuracy (0.917) compared to other models, with the highest kappa value (0.8846) and MCC value (0.8932). In addition, the performed sensitivity analysis showed that the deviation rate is the most important influencing factor, followed by the internal diameter of the pipeline. Eventually, the WOA–RF hybrid model was used to predict the failure risk level of the backfilling pipelines of nine actual mines in Sichuan, China. The field datasets were collected through field investigation, and engineering verification was carried out. The research results show that the WOA–RF hybrid model is reasonable and effective for backfilling pipeline invalidation risk, and it can provide a novel solution for backfilling pipeline invalidation, with good engineering practicability.
Correction: Back et al. A New Micromonospora Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge. Mar. Drugs 2021, 19, 105
Authors: Back Catherine R. , Stennett Henry L. , Williams Sam E. , Wang Luoyi , Ojeda Gomez Jorge , Abdulle Omar M. , Duffy Thomas , Neal Christopher , Mantell Judith , Jepson Mark A. , Hendry Katharine R. , Powell David , Stach James E. M. , Essex-Lopresti Angela E. , Willis Christine L. , Curnow Paul , Race Paul R.
Published: March 2023

After publication of this article [...]
Analysis of Uneven Wear Mechanism of Narrow-Face Copper Wall of Funnel Mold
Authors: Liu Zengxun , Yang Yaosen , Xiao Pengcheng , Zhu Liguang , Zhang Luping
Published: March 2023

In thin-slab continuous casting, due to the influence of the special shape of the funnel mold, cracks at the corner of the slab shell are more likely to occur than those in conventional slab shells, and a serious wear phenomenon also appears on the narrow face of the copper wall of the mold. Aimed at the corner cracks of thin slabs and the wear phenomenon of the copper wall, a new 3D stress analysis model in a funnel mold has been developed to simulate the stress-–train behavior of the slab shell under high-speed continuous casting. The results show that at the position 600 mm below the meniscus, the gap begins to appear at the corner of the slab; the maximum value of the first principal stress appears at the corner. The shell is squeezed by the copper wall during the downward movement in the funnel mold, and the slab shell in the funnel area moves towards the narrow face. The displacement causes the deformation of the slab shell to extend to the corners, the deformed shell is pressed against the corner of the copper wall. A new type of copper wall was designed for production, and it was found that the cracks at the corner of the slab shell were greatly reduced.
Prevalence of Oral Pathogen Slackia exigua among Clinical Orthodontic and Non-Orthodontic Saliva Samples
Authors: Shen Ching , Simpson Justin , Clawson James Brigham , Lam Steven , Kingsley Karl
Published: March 2023

Slackia exigua (SE) is a recently identified intestinal microbe, which recent oral surveys suggest may be associated with oral diseases including caries and periodontal disease. Based upon the lack of information regarding this organism, the primary objective of this study was to determine the oral prevalence of this microbe and any potential associations with patient characteristics such as age, sex, or the presence of orthodontic appliances. This retrospective study involved the screening of an existing saliva repository composed of previously collected unstimulated clinical saliva samples. More specifically, N = 266 were identified and screened using a spectrophotometer at absorbances of A260 and A280 nm to determine their DNA purity and concentration. qPCR screening of these samples revealed a higher prevalence of Slackia exigua positive samples among pediatric patients (63.1%) compared with adults (36.9%) in this clinic population, p = 0.0007. In addition, higher percentages of Slackia exigua were observed among orthodontic patients (71.2%) compared with non-orthodontic patients (28.8%), p = 0.0001. These results did not vary by sex with nearly equal percentages of Slackia exigua positive males and females among adult and pediatric patients, as well as orthodontic and non-orthodontic samples. These results suggest a strong potential for association between the prevalence of this organism with age as well as orthodontic status, given that younger patients and those with orthodontic brackets (regardless of age) were most likely to harbor this pathogen in sufficient levels to be detected in saliva. More research will be needed to determine any associations with specific outcomes, such as caries or periodontal disease, among Slackia exigua positive patients within these specific populations.
Accelerated Synthesis of Borophane (HB) Sheets through HCl-Assisted Ion-Exchange Reaction with YCrB4
Authors: Zhang Xiaoni , Hikichi Miwa , Iimori Takushi , Tsujikawa Yuki , Yuan Mei , Horio Masafumi , Yubuta Kunio , Komori Fumio , Miyauchi Masahiro , Kondo Takahiro , Matsuda Iwao
Published: March 2023

We present an enhanced method for synthesizing sheets of borophane. Despite the challenges associated with low efficiency, we discovered that incorporating hydrochloric acid into the ion-exchange reaction significantly improved the production yield from 20% to over 50%. After a thorough examination of the reaction, we gained insight into the underlying mechanisms and found that the use of hydrochloric acid provides two key benefits: accelerated production of borophene and isolation of high-purity products. This method has the potential to pave the way for the production of novel topological 2D materials with potential industrial applications.
Polyhedral Dicobaltadithiaboranes and Dicobaltdiselenaboranes as Examples of Bimetallic Nido Structures without Bridging Hydrogens
Authors: Attia Amr A. A. , Lupan Alexandru , King Robert Bruce
Published: March 2023

The geometries and energetics of the n-vertex polyhedral dicobaltadithiaboranes and dicobaltadiselenaboranes Cp2Co2E2Bn−4Hn−4 (E = S, Se; n = 8 to 12) have been investigated via the density functional theory. Most of the lowest-energy structures in these systems are generated from the (n + 1)-vertex most spherical closo deltahedra by removal of a single vertex, leading to a tetragonal, pentagonal, or hexagonal face depending on the degree of the vertex removed. In all of these low-energy structures, the chalcogen atoms are located at the vertices of the non-triangular face. Alternatively, the central polyhedron in most of the 12-vertex structures can be derived from a Co2E2B8 icosahedron with adjacent chalcogen (E) vertices by breaking the E–E edge and 1 or more E–B edges to create a hexagonal face. Examples of the arachno polyhedra with two tetragonal and/or pentagonal faces derived from the removal of two vertices from isocloso deltahedra were found among the set of lowest-energy Cp2Co2E2Bn−4Hn−4 (E = S, Se; n = 8 and 12) structures.
Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19: A Computational Molecular Docking and Dynamic Simulation Approach
Authors: Naz Aliza , Asif Sumbul , Alwutayd Khairiah Mubarak , Sarfaraz Sara , Abbasi Sumra Wajid , Abbasi Asim , Alenazi Abdulkareem M. , Hasan Mohamed E.
Published: March 2023

Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit acid sphingomyelinase activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 into the cells. To achieve our objective, a drug library containing 257 functional inhibitors of ASM was constructed. Computational molecular docking was applied to dock the library against the target protein (PDB: 5I81). The potential binding site of the target protein was identified through structural alignment with the known binding pocket of a protein with a similar function. AutoDock Vina was used to carry out the docking steps. The docking results were analyzed and the inhibitors were screened based on their binding affinity scores and ADME properties. Among the 257 functional inhibitors, Dutasteride, Cepharanthine, and Zafirlukast presented the lowest binding affinity scores of −9.7, −9.6, and −9.5 kcal/mol, respectively. Furthermore, computational ADME analysis of these results revealed Cepharanthine and Zafirlukast to have non-toxic properties. To further validate these findings, the top two inhibitors in complex with the target protein were subjected to molecular dynamic simulations at 100 ns. The molecular interactions and stability of these compounds revealed that these inhibitors could be a promising tool for inhibiting SARS-CoV-2 infection.
Recent Advances of N-2,2,2-Trifluoroethylisatin Ketimines in Organic Synthesis
Authors: Liu Yuting , Wang Lijie , Ma Donglai , Song Yongxing
Published: March 2023

The special properties of fluorine atoms and fluorine-containing groups have led to an increasing number of applications for fluorine-containing organic compounds, which are also extremely widely used in the field of new drug development. Unfortunately, naturally fluorinated organics are rare in nature, so the selective introduction of fluorine atoms or fluorine-containing groups into organic molecules is very important for pharmaceutical/synthetic chemists. N-2,2,2-trifluoroethylisatin ketimines have received the attention of many chemists since they were first developed as fluorine-containing synthons in 2015. This paper reviews the organic synthesis reactions in which trifluoroethyl isatin ketimine has been involved in recent years, focusing on the types of reactions and the stereoselectivity of products, and also provides a prospect of its application in this field.
Preliminary Study on Insecticidal Potential and Chemical Composition of Five Rutaceae Essential Oils against Thrips flavus (Thysanoptera: Thripidae)
Authors: Pei Tian-Hao , Zhao Yi-Jin , Wang Sheng-Yuan , Li Xiao-Feng , Sun Chen-Qi , Shi Shu-Sen , Xu Meng-Lei , Gao Yu
Published: March 2023

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm−2, 97.22 ± 1.39% at 720 g a.i.·hm−2, 100.00% at 900.00 g a.i.·hm−2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm−2), and pomelo peel oil (100.00% at 900 g a.i.·hm−2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography–mass spectrometry (GC–MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.
Rational Design and Lead Optimisation of Potent Antimalarial Quinazolinediones and Their Cytotoxicity against MCF-7
Authors: Charoensutthivarakul Sitthivut , Lohawittayanan Duangporn , Kanjanasirirat Phongthon , Jearawuttanakul Kedchin , Seemakhan Sawinee , Chabang Napason , Schlaeppi Patrick , Tantivess Varisa , Limboonreung Tanapol , Phanchana Matthew
Published: March 2023

Quinazolinedione is one of the most outstanding heterocycles in medicinal chemistry thanks to its wide ranges of biological activities including antimalarial, anticancer, and anti-inflammatory. TCMDC-125133 containing a quinazolinedione pharmacophore displays promising antimalarial activity and low toxicity, as described in the GlaxoSmithKline (GSK) report. Herein, the design and synthesis of novel quinazolinedione derivatives is described on the basis of our previous work on the synthesis of TCMDC-125133, where low-cost chemicals and greener alternatives were used when possible. The initial SAR study focused on the replacement of the valine linker moiety; according to the in silico prediction using SwissADME, concise four-step syntheses toward compounds 4–10 were developed. The in-house synthesized compounds 4–10 were assayed for antimalarial activity against P. falciparum 3D7, and the result revealed that only the compound 2 containing a valine linker was tolerated. Another round of lead optimization focused on the replacement of the m-anisidine moiety in compound 2. A library of 12 derivatives was prepared, and the antimalarial assay showed that potent antimalarial activity could be maintained by replacing the methoxy group in the meta position of the phenyl side chain with a fluorine or chlorine atom (21: IC50 = 36 ± 5 nM, 24: IC50 = 22 ± 5 nM). Further lead optimization is underway to enhance the antimalarial activity of this class of compound. The compounds included in the study possess little to no antiproliferative activity against MCF-7 cells.
DABCO-Catalyzed Mono-/Diallylation of N-Unsubstituted Isatin N,N′-Cyclic Azomethine Imine 1,3-Dipoles with Morita-Baylis-Hillman Carbonates
Authors: Wang Qiumi , Li Sicheng , Yang Guosheng , Zou Xinyu , Yin Xi , Feng Juhua , Chen Huabao , Yang Chunping , Zhang Li , Lu Cuifen , Yue Guizhou
Published: March 2023

Allylation of N-unsubstituted isatin N,N′-cyclic azomethine imines with Morita-Baylis-Hillman carbonates in the presence of 1–10 mol% DABCO in DCM at room temperature, rapidly gave N-allylated and N, β-diallylated isatin N,N′-cyclic azomethine imine 1,3-dipoles in moderate to high yields. The reaction features mild reaction conditions, easily practical operation, and short reaction times in most cases. Furthermore, the alkylated products were transformed into novel bicyclic spiropyrrolidine oxoindole derivatives through the [3+2] or [3+3]-cycloaddition with maleimides or Knoevenagel adducts.
Intramolecular and Intermolecular Interaction Switching in the Aggregates of Perylene Diimide Trimer: Effect of Hydrophobicity
Authors: Su Peiyuan , Ran Guangliu , Wang Hang , Yue Jianing , Kong Qingyu , Bo Zhishan , Zhang Wenkai
Published: March 2023

The research on perylene diimide (PDI) aggregates effectively promotes their applications in organic photovoltaic solar cells and fluorescent sensors. In this paper, a PDI fabricated with three peripheral PDI units (N, N’-bis(6-undecyl) perylene-3,4,9,10-bis(dicarboximide)) is investigated. The trimer shows different absorption and fluorescence properties due to hydrophobicity when dissolved in the mixed solvent of tetrahydrofuran (THF) and water. Through comprehensive analysis of the fluorescence lifetime and transient absorption spectroscopic results, we concluded that the trimer underwent different excited state kinetic pathways with different concentrations of water in THF. When dissolved in pure THF solvent, both the intramolecular charge-transfer and excimer states are formed. When the water concentration increases from 0 to 50% (v/v), the formation time of the excimer state and its structural relaxation time are prolonged, illustrating the arising of the intermolecular excimer state. It is interesting to determine that the probability of the intramolecular charge-transfer pathway will first decrease and then increase as the speed of intermolecular excimer formation slows down. The two inflection points appear when the water concentration is above 10% and 40%. The results not only highlight the importance of hydrophobicity on the aggregate properties of PDI multimers but also guide the further design of PDI-based organic photovoltaic solar cells.
Fe–Decorated Nitrogen–Doped Carbon Nanospheres as an Electrochemical Sensing Platform for the Detection of Acetaminophen
Authors: Zhao Xiangchuan , Zhang Liping , Chu Zhaoyun , Wang Qing , Cao Yue , Cao Jun , Li Jiao , Lei Wu , Zhang Boming , Si Weimeng
Published: March 2023

In this work, Fe–decorated nitrogen–doped carbon nanospheres are prepared for electrochemical monitoring of acetaminophen. Via a direct pyrolysis of the melamine–formaldehyde resin spheres, the well–distributed Fe–NC spheres were obtained. The as–prepared Fe–NC possesses enhanced catalysis towards the redox of acetaminophen for abundant active sites and high–speed charge transfer. The effect of loading Fe species on the electrochemical sensing of acetaminophen is investigated in detail. The synergistic effect of nitrogen doping along with the above–mentioned properties is taken advantage of in the fabrication of electrochemical sensors for the acetaminophen determination. Based on the calibration plot, the limits of detection (LOD) were calculated to be 0.026 μM with a linear range from 0–100 μM. Additionally satisfactory repeatability, stability, and selectivity are obtained.
Histamine and Tyramine in Chihuahua Cheeses during Shelf Life: Association with the Presence of tdc and hdc Genes
Authors: Campos-Góngora Eduardo , González-Martínez María Teresa , López-Hernández Abad Arturo , Arredondo-Mendoza Gerardo Ismael , Ortega-Villarreal Ana Sofía , González-Martínez Blanca Edelia
Published: March 2023

Cheese is a product of animal origin with a high nutritional value, and it is one of the most consumed dairy foods in Mexico. In addition, Chihuahua cheese is the most consumed matured cheese in Mexico. In the production process of Chihuahua cheese, maturation is carried out by adding acid lactic microorganisms, mainly of the Lactococcus genus and, in some cases, also the Streptococcus and Lactobacillus genus. As part of the metabolism of fermenting microorganisms, biogenic amines can develop in matured foods, which result from the activity of amino decarboxylase enzymes. In cheeses, histamine and tyramine are the main amines that are formed, and the consumption of these represents a great risk to the health of consumers. In this work, the presence of biogenic amines (histamine and tyramine) was determined by HPLC at different times of the shelf life of Chihuahua cheeses. In addition, the presence of genes hdc and tdc that code for the enzymes responsible for the synthesis of these compounds (histidine and tyrosine decarboxylase, or HDC and TDC) was determined by molecular techniques. A significant correlation was observed between the presence of both histamine and tyramine at the end of shelf life with the presence of genes that code for the enzymes responsible for their synthesis.
Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy
Authors: Alafaleq Nouf Omar , Zughaibi Torki A. , Jabir Nasimudeen R. , Khan Azhar U. , Khan Mohd Shahnawaz , Tabrez Shams
Published: March 2023

Background: Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). Methods: The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. Results: The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. Conclusions: The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model.
Associations of Homocysteine, Folate, and Vitamin B12 with Osteoarthritis: A Mendelian Randomization Study
Authors: Hong Haofeng , Chen Longting , Zhong Yiming , Yang Zihuan , Li Weishi , Song Chunli , Leng Huijie
Published: March 2023

Homocysteine, inversely related to folate and vitamin B12, is an independent risk factor for several age-related disorders. However, little is known about the association of homocysteine and related vitamins with osteoarthritis (OA). This study aimed to elucidate the potential causal effects of homocysteine, folate, and vitamin B12 on site- and gender-specific OA by applying the two-sample Mendelian randomization (MR) approach. Genetically predicted homocysteine showed adverse effects on overall OA (95% confidence interval (CI): 1.044–1.155), knee OA (95% CI: 1.000–1.167), hip OA (95% CI: 1.057–1.297), and spine OA (95% CI: 1.017–1.216). Genetically predicted folate showed protective effects on overall OA (95% CI: 0.783–0.961) and spine OA (95% CI: 0.609–0.954). Folate (95% CI: 0.887–1.004) and vitamin B12 (95% CI: 0.886–1.009) showed a protective trend against knee OA. The patterns of associations were site and gender specific. In conclusion, homocysteine had adverse effects on OA, especially on OA at weight-bearing joints and in females. Folate and vitamin B12 had protective effects on OA. Homocysteine-lowering interventions may be a potential option in the treatment and prevention of OA.
Impact of Regular Intake of Microalgae on Nutrient Supply and Cardiovascular Risk Factors: Results from the NovAL Intervention Study
Authors: Sandgruber Fabian , Höger Anna-Lena , Kunze Julia , Schenz Benjamin , Griehl Carola , Kiehntopf Michael , Kipp Kristin , Kühn Julia , Stangl Gabriele I. , Lorkowski Stefan , Dawczynski Christine
Published: March 2023

A 14-day randomized controlled study with a parallel design was conducted with 80 healthy participants. Intervention groups I (IG1) and II (IG2) received a defined background diet and consumed a smoothie enriched with either 15 g of Chlorella dry weight (d.w.) or 15 g of Microchloropsis d.w. daily. Control group II (CG2) received a defined background diet without the smoothie. Control group I (CG1) received neither. Blood samples and 24-h urine were collected at the beginning and the end of the study. Serum concentrations of 25-hydroxyvitamin D3, vitamin D3, selenium, iron, ferritin, transferrin saturation, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol and the LDL-cholesterol/HDL cholesterol ratio decreased in IG1 (p < 0.05), while 25-hydroxyvitamin D2 increased (p < 0.05). In IG2, vitamin D3, 25-hydroxyvitamins D2 and D3 decreased (p < 0.05), while concentrations of fatty acids C20:5n3 and C22:5n3 increased. Serum and urine uric acid increased in IG1 and IG2 (p < 0.05). Microchloropsis is a valuable source of n3 fatty acids, as is Chlorella of vitamin D2. Regular consumption of Chlorella may affect the iron and selenium status negatively but may impact blood lipids positively. An elevated uric acid concentration in blood and urine following the regular consumption of microalgae poses potential risks for human health.
Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells
Authors: Martínez-Razo Gabriel , Pires Patrícia C. , Domínguez-López María Lilia , Veiga Francisco , Vega-López Armando , Paiva-Santos Ana Cláudia
Published: March 2023

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/− 0.370 mg/kg, and the cells’ metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new “easy-to-make” nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.