bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Alloying Elements on the Mechanical Properties of Anodized Aluminum and on the Adhesion of Copper Metallization
Authors: Medvedev Oleg S. , Alyasova Ekaterina E. , Besprozvannaya Rona E. , Gadzhiev Asadula A. , Krivova Veronika V. , Kondratev Andrey S. , Kim Artem E. , Novikov Pavel A. , Popovich Anatoliy A.
Published: November 2021

The active development of the power electronics market and a constant increase in the prices of components require new materials and approaches, including a power module packaging technology. The use of aluminum instead of copper in the power module baseplate is an interesting and promising solution. The insulated metal baseplate is one of the most extensively developed technologies nowadays. The object of this study is an insulated metal substrate based on anodized aluminum. The main goal of the article is the comparison of copper topology adhesion to an anodized aluminum oxide layer formed on different aluminum alloys with aluminum content of at least 99.3 wt %. Peel test and pull-off adhesions showed a twofold difference for both aluminum alloys. The high ordered defect-free anodized alumina formed on alloys with copper content of 0.06 wt % had a mean pull-off adhesion of 27 N/mm2 and hardness of 489 HV. In the case of the alloy with copper content of around 0.15 wt %, it had hardness of 295 HV and a mean pull-off adhesion of 12 N/mm2. The results of our microstructure investigation showed that anodized alumina based on alloys with copper content of around 0.15 wt % is fragile due to spherical holes. Summing up the results, it can be concluded that not all initial impurities are critical for anodized alumina, but some, specifically copper, dramatically decreased the mechanical properties of anodized alumina.
Structure and Phase State of Ti49.4Ni50.6 (at%) Hydrogenated in Normal Saline
Authors: Grishkov Victor , Lotkov Aleksandr , Zhapova Dorzhima , Mironov Yuri , Timkin Victor , Barmina Elena , Kashina Olga
Published: November 2021

The paper analyzes the surface structure and phase state of Ti49.4Ni50.6 (at%) hydrogenated at 295 K in normal saline (0.9% NaCl aqueous solution with pH = 5.7) at 20 A/m2 for 0.5–6 h. The analysis shows that the average hydrogen concentration in the alloy increases with the hydrogenation time tH as follows: slowly to 50 ppm at tH = 0.5–1.5 h, steeply to 150 ppm at tH = 1.2–2 h, and linearly to 300 ppm at tH = 2–6 h. According to Bragg–Brentano X-ray diffraction data (θ–2 θ, 2 θ ≤ 50°, CoKα radiation), the alloy in its scanned surface layer of thickness ~5.6 µm reveals a TiNiHx phase with x = 0.64 and x = 0.54 after hydrogenation for 4 and 6 h, respectively. The structure of this phase is identifiable as an orthorhombic hydride similar to β1–TiFeH0.94 (space group Pmcm), rather than as a tetragonal TiNiHx hydride with x = 0.30–1.0 (space group I4/mmm). Time curves are presented to trace the lattice parameters and volume change during the formation of such an orthorhombic phase from the initial cubic B2 phase in Ti49.4Ni50.6 (at%).
Investigation of the Impact of Graphene Nanoplatelets (GnP) on the Bond Stress of High-Performance Concrete Using Pullout Testing
Authors: Ismail Fouad Ismail , Abbas Yassir M. , Shafiq Nasir , Fares Galal , Osman Montasir , Hussain Lotfi A. , Khan Mohammad Iqbal
Published: November 2021

Efficient load transmission between concrete and steel reinforcement by bonding action is a key factor in the process of the design procedure of bar-reinforced concrete structures. To enhance the bond strength of steel/concrete composites, the impact of graphene nanoplatelets (GnP) on the bond stress and bond stress–slip response of deformed reinforcement bars, embedded in high-performance concrete (HPC), was investigated using bar pullout tests. In the current study, 36 samples were produced and examined. The main variables were the percentages of GnP, the steel reinforcement bar diameter, and embedded length. Bond behavior, failure mode, and bond stress-slip response were studied. Based on the experimental findings, the inclusion of GnP had a significant favorable influence on the bar-matrix interactions due to the bridging action of GnP as a nano reinforcement. For 0.02 wt.% of GnP, the bond strength was enhanced by more than 41.28% and 53.90% for steel bar diameters of 10 and 16 mm, respectively. The HPC-GnP mixture displayed a reduction in the initial slippage in comparison to the control sample. The test findings were compared to the prediction models created by other researchers and the ACI 408R-12 code.
Application of Modern Research Methods for the Physicochemical Characterization of Ion Exchangers
Authors: Chen Yi-Gong , Sofińska-Chmiel Weronika , Lv Gui-Yuan , Kołodyńska Dorota , Chen Su-Hong
Published: November 2021

Ion exchange technique as the reversible exchange of ions between the substrate and the surrounding medium can be an effective way of removing traces of ion impurities from the waters and wastewaters and obtaining a product of ultrapure quality. Therefore, it can be used in analytical chemistry, hydrometallurgy, purification and separation of metal ions, radioisotopes and organic compounds, and it also finds great application in water treatment and pollution control. In the presented paper, the new trends for ion exchanger characteristics determination and application are presented. Special attention is paid to the ion exchangers with multifunctionality for heavy metal ions removal. They show superior actions such as sorption capacity values with excellent resistance to fouling and the possibility of application in the co-current or modern packed bed counter-current systems, as well as for the condensate polishing or the conventional mixed bed systems in combination with other resins. The results of the paper are expected to help researchers to establish a powerful strategy to find a suitable ion exchanger for heavy metal ions removal from waters and wastewaters. It is important because the best ion exchangers are selected for a specific application during laboratory tests taking into account the composition of the feed solution, pH, type of ion exchangers and then the column breakthrough tests. Therefore, the optical profilometry and the X-ray photoelectron spectroscopy can prove beneficial for this purpose in the case of three different ion exchangers such as Dowex M 4195, Amberlite IRA 743 and Purolite Arsen Xnp.
An Investigation on Substitution of Ag Atoms for Al or Ti Atoms in the Ti2AlC MAX Phase Ceramic Based on First-Principles Calculations
Authors: Wang Guochao , Zhou Jiahe , Chen Weijian , Yang Jianguo , Zhang Jie , He Yanming
Published: November 2021

The present work introduced first-principles calculation to explore the substitution behavior of Ag atoms for Al or Ti atoms in the Ti2AlC MAX phase ceramic. The effect of Ag substitution on supercell parameter, bonding characteristic, and stability of the Ti2AlC was investigated. The results show that for the substitution of Ag for Al, the Al-Ti bond was replaced by a weaker Ti-Ag bond, decreasing the stability of the Ti2AlC. However, the electrical conductivity of the Ti2AlC was enhanced after the substitution because of the contribution of Ag 4d orbital electrons toward the density of states (DOS) at the Fermi level coupled with the filling of Ti d orbital electrons. For the substitution of Ag for Ti, new bonds, such as Ag-Al bond, Ag-C bond, Al-Al bond, Ti-Ti anti-bond, and C-C anti-bond were generated in the Ti2AlC. The Ti-Ti anti-bond was strengthened as well as the number of C-C anti-bond was increased with increasing the substitution ratio of Ag for Ti. Similar to the substitution of Ag for Al, the stability of the Ti2AlC also decreased because the original Al-Ti bond became weaker as well as the Ti-Ti and C-C anti-bonds were generated during the substitution of Ag for Ti. Comparing with the loss of Ti d orbital electrons, Ag 4d orbits contributed more electrons to the DOS at the Fermi level, improving the electrical conductivity of the Ti2AlC after substitution. Based on the calculation, the substitution limit of Ag for Al or Ti was determined. At last, the substitution behavior of Ag for Al or Ti was compared to discriminate that Ag atoms would tend to preferentially substitute for Ti atoms in Ti2AlC. The current work provides a new perspective to understand intrinsic structural characteristic and lattice stability of the Ti2AlC MAX phase ceramic.
The Distributed and Centralized Fusion Filtering Problems of Tessarine Signals from Multi-Sensor Randomly Delayed and Missing Observations under Tk-Properness Conditions
Authors: Jiménez-López José D. , Fernández-Alcalá Rosa M. , Navarro-Moreno Jesús , Ruiz-Molina Juan C.
Published: November 2021

This paper addresses the fusion estimation problem in tessarine systems with multi-sensor observations affected by mixed uncertainties when under Tk-properness conditions. Observations from each sensor can be updated, delayed, or contain only noise, and a correlation is assumed between the state and the observation noises. Recursive algorithms for the optimal local linear filter at each sensor as well as both centralized and distributed linear fusion estimators are derived using an innovation approach. The Tk-properness assumption implies a reduction in the dimension of the augmented system, which yields computational savings in the previously mentioned algorithms compared to their counterparts, which are derived from real or widely linear processing. A numerical simulation example illustrates the obtained theoretical results and allows us to visualize, among other aspects, the insignificant difference in the accuracy of both fusion filters, which means that the distributed filter, although suboptimal, is preferable in practice as it implies a lower computational cost.
Overview in Summabilities: Summation Methods for Divergent Series, Ramanujan Summation and Fractional Finite Sums
Authors: Chagas Jocemar Q. , Machado José A. Tenreiro , Lopes António M.
Published: November 2021

This work presents an overview of the summability of divergent series and fractional finite sums, including their connections. Several summation methods listed, including the smoothed sum, permit obtaining an algebraic constant related to a divergent series. The first goal is to revisit the discussion about the existence of an algebraic constant related to a divergent series, which does not contradict the divergence of the series in the classical sense. The well-known Euler–Maclaurin summation formula is presented as an important tool. Throughout a systematic discussion, we seek to promote the Ramanujan summation method for divergent series and the methods recently developed for fractional finite sums.
Parameter Identification of Optimized Fractional Maximum Power Point Tracking for Thermoelectric Generation Systems Using Manta Ray Foraging Optimization
Authors: Fathy Ahmed , Rezk Hegazy , Yousri Dalia , Houssein Essam H. , Ghoniem Rania M.
Published: November 2021

Thermoelectric generation systems (TEGSs) are used to convert temperature difference and heat flow into DC power based on the Seebeck theorem. The basic unit of TEGS is the thermoelectric module (TEM). TEGSs have gained increasing interest in the research fields of sustainable energy. The output power from TEM is mostly reliant on differential temperature between the hot and cold sides of the TEM added to the value of the load. As such, a robust MPPT strategy (MPPTS) is required to ensure that the TEGS is operating near to the MPP while varying the operating conditions. Two main drawbacks may occur in the conventional MPPTSs: low dynamic response, such as in the incremental resistance (INR) method, and oscillations around MPP at steady state, such as in the hill climbing (HC) method. In the current research work, an optimized fractional MPPTS is developed to improve the tracking performance of the TEGS, and remove the two drawbacks of the conventional MPPTSs. The proposed strategy is based on fractional order control (FOC). The main advantage of FOC is that it offers extra flexible time and frequency responses of the control system consent for better and robust performance. The optimal parameters of the optimized fractional MPPTS are identified by a manta ray foraging optimization (MRFO). To verify the robustness of the MRFO, the obtained results are compared with ten other algorithms: particle swarm optimization; whale optimization algorithm; Harris hawks optimization; heap-based optimizer; gradient-based optimizer; grey wolf optimizer; slime mould algorithm; genetic algorithm; seagull optimization algorithm (SOA); and tunicate swarm algorithm. The maximum average cost function of 4.92934 kWh has been achieved by MRFO, followed by SOA (4.5721 kWh). The lowest STD of 0.04867 was also accomplished by MRFO. The maximum efficiency of 99.46% has been obtained by MRFO, whereas the lowest efficiency of 74.01% was obtained by GA. Finally, the main findings proved the superiority of optimized fractional MPPTS compared with conventional methods for both steady-state and dynamic responses.
Staggered Semi-Implicit Hybrid Finite Volume/Finite Element Schemes for Turbulent and Non-Newtonian Flows
Authors: Busto Saray , Dumbser Michael , Río-Martín Laura
Published: November 2021

This paper presents a new family of semi-implicit hybrid finite volume/finite element schemes on edge-based staggered meshes for the numerical solution of the incompressible Reynolds-Averaged Navier–Stokes (RANS) equations in combination with the k−ε turbulence model. The rheology for calculating the laminar viscosity coefficient under consideration in this work is the one of a non-Newtonian Herschel–Bulkley (power-law) fluid with yield stress, which includes the Bingham fluid and classical Newtonian fluids as special cases. For the spatial discretization, we use edge-based staggered unstructured simplex meshes, as well as staggered non-uniform Cartesian grids. In order to get a simple and computationally efficient algorithm, we apply an operator splitting technique, where the hyperbolic convective terms of the RANS equations are discretized explicitly at the aid of a Godunov-type finite volume scheme, while the viscous parabolic terms, the elliptic pressure terms and the stiff algebraic source terms of the k−ε model are discretized implicitly. For the discretization of the elliptic pressure Poisson equation, we use classical conforming P1 and Q1 finite elements on triangles and rectangles, respectively. The implicit discretization of the viscous terms is mandatory for non-Newtonian fluids, since the apparent viscosity can tend to infinity for fluids with yield stress and certain power-law fluids. It is carried out with P1 finite elements on triangular simplex meshes and with finite volumes on rectangles. For Cartesian grids and more general orthogonal unstructured meshes, we can prove that our new scheme can preserve the positivity of k and ε. This is achieved via a special implicit discretization of the stiff algebraic relaxation source terms, using a suitable combination of the discrete evolution equations for the logarithms of k and ε. The method is applied to some classical academic benchmark problems for non-Newtonian and turbulent flows in two space dimensions, comparing the obtained numerical results with available exact or numerical reference solutions. In all cases, an excellent agreement is observed.
First Report of OvoA Gene in Marine Arthropods: A New Candidate Stress Biomarker in Copepods
Authors: Roncalli Vittoria , Lauritano Chiara , Carotenuto Ylenia
Published: November 2021

Ovothiol is one of the most powerful antioxidants acting in marine organisms as a defense against oxidative stress during development and in response to environmental cues. The gene involved in the ovothiol biosynthesis, OvoA, is found in almost all metazoans, but open questions existed on its presence among arthropods. Here, using an in silico workflow, we report a single OvoA gene in marine arthropods including copepods, decapods, and amphipods. Phylogenetic analyses indicated that OvoA from marine arthropods separated from the other marine phyla (e.g., Porifera, Mollusca) and divided into two separate branches, suggesting a possible divergence through evolution. In the copepod Calanus finmarchicus, we suggest that OvoA has a defense role in oxidative stress as shown by its high expression in response to a toxic diet and during the copepodite stage, a developmental stage that includes significant morphological changes. Overall, the results of our study open possibilities for the use of OvoA as a biomarker of stress in copepods and possibly also for other marine holozooplankters. The finding of OvoA in copepods is also promising for the drug discovery field, suggesting the possibility of using copepods as a new source of bioactive compounds to be tested in the marine biotechnological sector.
Clinical and Histopathological Features of Scleroderma-like Disorders: An Update
Authors: Foti Rosario , De Pasquale Rocco , Dal Bosco Ylenia , Visalli Elisa , Amato Giorgio , Gangemi Pietro , Foti Riccardo , Ramondetta Alice
Published: November 2021

Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms responsible for different clinical–pathological pictures. The absence of antinuclear antibodies (ANA), Raynaud’s phenomenon and capillaroscopic anomalies constitutes an important element of differential diagnosis with systemic sclerosis. When scleroderma can be excluded, on the basis of the main body sites, clinical evolution, any associated pathological conditions and specific histological features, it is possible to make a correct diagnosis.
Parvovirus B19 in Croatia: A Large-Scale Seroprevalence Study
Authors: Vilibic-Cavlek Tatjana , Tabain Irena , Kolaric Branko , Mihulja Klara , Blazevic Lana , Bogdanic Maja , Navolan Dan , Beader Natasa , Mrzljak Anna
Published: November 2021

Background and Objectives: Seroepidemiological studies indicate that parvovirus B19 circulates in all areas of the world, although with some differences. The aim of this study is to analyze the seroprevalence of parvovirus B19 in the Croatian population. Materials and Methods: From 2010 to 2021, 1538 serum samples from different populations were tested for the presence of parvovirus B19 IgM/IgG antibodies. Serological tests were performed using a commercial enzyme-linked immunosorbent assay. Results: IgG antibodies were detected in 986/64.1% of participants with differences (p < 0.001) among the following population groups: 42.4% of children and adolescents, 67.1% of the adult general population, 66.7% of hemodialysis patients, and 65.6% of liver transplant recipients. Seroprevalence increased with age, from 30.0% in the 6 months–9 years age group to 69.0% in the 40–49 years age group, and remained stable thereafter (68.8–73.3%). There was no difference in the seropositivity among males (66.1%) and females (63.1%), as well as the place of residence (suburban/rural 63.9%, urban 64.1%). IgM antibodies (current/recent infection) were found in 61/4.0% of participants with the highest seropositivity in the youngest age group (11.1%). In pregnant women, seroprevalence was higher in women with an unfavorable obstetric history compared with a normal pregnancy (IgG 71.0% vs. 62.6%; IgM 6.5% vs. 2.4%), but these differences were not significant. Logistic regression showed that the adult population had almost three times higher risk of IgG seropositivity compared to children/adolescents (general population OR = 2.777, 95% CI = 2.023–3.812; hemodialysis patients OR = 2.586, 95% CI = 1.531–4.367; and transplant patients OR = 2.717, 95% CI = 1.604–4.603). A one-year increase in age increased the risk of IgG seroprevalence (OR = 1.017; 95% CI = 1.011–1.022). Conclusions: Older age was the main risk factor for IgG seropositivity. Hemodialysis and organ transplantation seem unrelated to the increased parvovirus B19 seroprevalence. The role of parvovirus B19 in the etiology of TORCH infections needs to be studied further.
Micromachined Tactile Sensor Array for RTSA
Authors: Leinauer Elliott C. , Kim H. Mike , Kwon Jae W.
Published: November 2021

This work presents a polymer-based tactile capacitive sensor capable of measuring joint reaction forces of reverse total shoulder arthroplasty (RTSA). The capacitive sensor contains a polydimethylsiloxane (PDMS) dielectric layer with an array of electrodes. The sensor was designed in such a way that four components of glenohumeral contact forces can be quantified to help ensure proper soft tissue tensioning during the procedure. Fabricated using soft lithography, the sensor has a loading time of approximately 400 ms when a 14.13 kPa load is applied and has a sensitivity of 1.24 × 10−3 pF/kPa at a load of 1649 kPa. A replica RTSA prothesis was 3D printed, and the sensor was mounted inside the humeral cap. Four static right shoulder positions were tested, and the results provided an intuitive graphical description of the pressure distribution across four quadrants of the glenohumeral joint contact surface. It may help clinicians choose a right implant size and offset that best fit a patient’s anatomy and reduce postoperative biomechanical complications such as dislocation and stress fracture of the scapula.
Neutrophils in Streptococcus suis Infection: From Host Defense to Pathology
Authors: Bleuzé Marêva , Gottschalk Marcelo , Segura Mariela
Published: November 2021

Streptococcus suis is a swine pathogen and zoonotic agent responsible for economic losses to the porcine industry. Infected animals may develop meningitis, arthritis, endocarditis, sepsis and/or sudden death. The pathogenesis of the infection implies that bacteria breach mucosal host barriers and reach the bloodstream, where they escape immune-surveillance mechanisms and spread throughout the organism. The clinical manifestations are mainly the consequence of an exacerbated inflammation, defined by an exaggerated production of cytokines and recruitment of immune cells. Among them, neutrophils arrive first in contact with the pathogens to combat the infection. Neutrophils initiate and maintain inflammation, by producing cytokines and deploying their arsenal of antimicrobial mechanisms. Furthermore, neutrophilic leukocytosis characterizes S. suis infection, and lesions of infected subjects contain a large number of neutrophils. Therefore, this cell type may play a role in host defense and/or in the exacerbated inflammation. Nevertheless, a limited number of studies addressed the role or functions of neutrophils in the context of S. suis infection. In this review, we will explore the literature about S. suis and neutrophils, from their interaction at a cellular level, to the roles and behaviors of neutrophils in the infected host in vivo.
Biomineralization Induced by Cells of Sporosarcina pasteurii: Mechanisms, Applications and Challenges
Authors: Wu Yang , Li Huimin , Li Yang
Published: November 2021

Biomineralization has emerged as a novel and eco-friendly technology for artificial mineral formation utilizing the metabolism of organisms. Due to its highly efficient urea degradation ability, Sporosarcina pasteurii(S. pasteurii) is arguably the most widely investigated organism in ureolytic biomineralization studies, with wide potential application in construction and environmental protection. In emerging, large-scale commercial engineering applications, attention was also paid to practical challenges and issues. In this review, we summarize the features of S. pasteurii cells contributing to the biomineralization reaction, aiming to reveal the mechanism of artificial mineral formation catalyzed by bacterial cells. Progress in the application of this technology in construction and environmental protection is discussed separately. Furthermore, the urgent challenges and issues in large-scale application are also discussed, along with potential solutions. We aim to offer new ideas to researchers working on the mechanisms, applications and challenges of biomineralization.
Production of Hydroxycarboxylic Acid Receptor 3 (HCA3) Ligands by Bifidobacterium
Authors: Sakurai Takuma , Horigome Ayako , Odamaki Toshitaka , Shimizu Takashi , Xiao Jin-Zhong
Published: November 2021

Hydroxycarboxylic acid receptor 3 (HCA3) was recently identified in the genomes of humans and other hominids but not in other mammals. We examined the production of HCA3 ligands by Bifidobacterium spp. In addition to 4-hydroxyphenyllactic acid, phenyllactic acid (PLA), and indole-3-lactic acid (ILA), we found that LeuA was produced by Bifidobacterium as an HCA3 ligand. The four ligands produced were the mixtures of enantiomers, and D-ILA, D-PLA, and D-LeuA showed stronger activity of the HCA3 ligand than their respective L-isomers. However, there was no difference in AhR activity between the two ILA enantiomers. These results provide new insights into the HCA3 ligands produced by Bifidobacterium and suggest the importance of investigating the absolute stereo structures of these metabolites.
Antiviral Therapeutic Potential of Curcumin: An Update
Authors: Ardebili Abdollah , Pouriayevali Mohammad Hassan , Aleshikh Sahar , Zahani Marziyeh , Ajorloo Mehdi , Izanloo Ahdieh , Siyadatpanah Abolghasem , Razavi Nikoo Hadi , Wilairatana Polrat , Coutinho Henrique Douglas Melo
Published: November 2021

The treatment of viral disease has become a medical challenge because of the increasing incidence and prevalence of human viral pathogens, as well as the lack of viable treatment alternatives, including plant-derived strategies. This review attempts to investigate the trends of research on in vitro antiviral effects of curcumin against different classes of human viral pathogens worldwide. Various electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar were searched for published English articles evaluating the anti-viral activity of curcumin. Data were then extracted and analyzed. The forty-three studies (published from 1993 to 2020) that were identified contain data for 24 different viruses. The 50% cytotoxic concentration (CC50), 50% effective/inhibitory concentration (EC50/IC50), and stimulation index (SI) parameters showed that curcumin had antiviral activity against viruses causing diseases in humans. Data presented in this review highlight the potential antiviral applications of curcumin and open new avenues for further experiments on the clinical applications of curcumin and its derivatives.
Theoretical Exploring of a Molecular Mechanism for Melanin Inhibitory Activity of Calycosin in Zebrafish
Authors: Tayier Nilupaier , Qin Ning-Yi , Zhao Li-Nan , Zeng Yi , Wang Yu , Hu Guang , Wang Yuan-Qiang
Published: November 2021

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin can lead to a variety of skin disorders. Calycosin is an isoflavone from Astragali Radix, which is a traditional Chinese medicine that exhibits several pharmacological activities including skin whitening. In our study, the inhibitory effect of calycosin on melanin production is confirmed in a zebrafish in vivo model by comparing with hydroquinone, kojic acid, and arbutin, known as tyrosinase inhibitors. Moreover, the inhibitory kinetics of calycosin on tyrosinase and their binding mechanisms are determined using molecular docking techniques, molecular dynamic simulations, and free energy analysis. The results indicate that calycosin has an obvious inhibitory effect on zebrafish pigmentation at the concentration of 7.5 μM, 15 μM, and 30 μM. The IC50 of calycosin is 30.35 μM, which is lower than hydroquinone (37.35 μM), kojic acid (6.51 × 103 μM), and arbutin (3.67 × 104 μM). Furthermore, all the results of molecular docking, molecular dynamics simulations, and free energy analysis suggest that calycosin can directly bind to the active site of tyrosinase with very good binding affinity. The study indicates that the combination of computer molecular modeling and zebrafish in vivo assay would be feasible in confirming the result of the in vitro test and illustrating the target-binding information.
Phytochemistry, Pharmacology, and Nutraceutical Profile of Carissa Species: An Updated Review
Authors: Dhatwalia Jyoti , Kumari Amita , Verma Rachna , Upadhyay Navneet , Guleria Ishita , Lal Sohan , Thakur Shabnam , Gudeta Kasahun , Kumar Vikas , Chao Jane C.-J. , Sharma Somesh , Kumar Ashwani , Manicum Amanda-Lee Ezra , Lorenzo José M. , Amarowicz Ryszard
Published: November 2021

Carissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania’s subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3β-hydroxyolean-11-en-28,13β-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.
Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
Authors: Orrapin Santhasiri , Roytrakul Sittiruk , Phaonakrop Narumon , Thaisakun Siriwan , Tragoolpua Khajornsak , Intorasoot Amornrat , McGill Suzanne , Burchmore Richard , Intorasoot Sorasak
Published: November 2021

The occurrence of Cryptococcus neoformans, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of C. neoformans with antifungal drugs resistance has become a global concern. Potential antifungal agents with extremely low toxicity are urgently needed. Herein, the biological activities of recombinant javanicin (r-javanicin) against C. neoformans were evaluated. A time-killing assay was performed and both concentration- and time-dependent antifungal activity of r-javanicin were indicated. The inhibitory effect of the peptide was initially observed at 4 h post-treatment and ultimately eradicated within 36 to 48 h. Fungal outer surface alteration was characterized by the scanning electron microscope (SEM) whereas a negligible change with slight shrinkage of external morphology was observed in r-javanicin treated cells. Confocal laser scanning microscopic analysis implied that the target(s) of r-javanicin is conceivably resided in the cell thereby allowing the peptide to penetrate across the membrane and accumulate throughout the fungal body. Finally, cryptococcal cells coped with r-javanicin were preliminarily investigated using label-free mass spectrometry-based proteomics. Combined with microscopic and proteomics analysis, it was clearly elucidated the peptide localized in the intracellular compartment where carbohydrate metabolism and energy production associated with glycolysis pathway and mitochondrial respiration, respectively, were principally interfered. Overall, r-javanicin would be an alternative candidate for further development of antifungal agents.
Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes
Authors: Koycheva Ivanka K. , Mihaylova Liliya V. , Todorova Monika N. , Balcheva-Sivenova Zhivka P. , Alipieva Kalina , Ferrante Claudio , Orlando Giustino , Georgiev Milen I.
Published: November 2021

Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (Harpagophytum procumbens (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced H. procumbens (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cells. Our results suggest that LEU may exhibit therapeutic potential against psoriasis by regulating keratinocyte differentiation through inhibition of the PI3K/AKT pathway.
Degradation of β-Carbolines Harman and Norharman in Edible Oils during Heating
Authors: Liu Wei , Yang Zhaoyu , Shi Lili , Cui Ziyu , Li Yun
Published: November 2021

The β-carbolines, mainly including harman and norharman, are a group of naturally occurring, plant-derived alkaloids, and are also considered as nonpolar heterocyclic aromatic amines. Sesame seed oils contain a high level of β-carbolines (harman and norharman). In China, sesame seed oil blends are one of the most popular types of vegetable oils blends, which can be used as cooking oils or frying oils. Thus, it is meaningful to investigate the degradation of β-carbolines (harman and norharman) in sesame seed oil blends as frying oils during heating. In this work, the loss of harman and norharman in different types of sesame seed oil blends have been investigated. The results showed that the degradation of harman and norharman were dependent both on the type of oil blends, heating temperature and time. Harman and norharman were more degraded during heating (150 °C, 180 °C) in oleic acid-rich oil blends compared to polyunsaturated acid-rich oil blends. Mechanistic investigation suggested that the reduction in harman and norharman in oil blends during heating was mainly due to the oxidative degradation reaction between β-carbolines and lipid oxidation products. Therefore, the contents of β-carbolines (harman and norharman) in sesame seed oil blends when used as frying oils and heated can be decreased with prolonged cooking time.
Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice
Authors: Albalawi Aishah E. , Althobaiti Norah A. , Alrdahe Salma Saleh , Alhasani Reem Hasaballah , Alaryani Fatima S. , BinMowyna Mona Nasser
Published: November 2021

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.
The Structural Determinants for α1-Adrenergic/Serotonin Receptors Activity among Phenylpiperazine-Hydantoin Derivatives
Authors: Kucwaj-Brysz Katarzyna , Dela Anna , Podlewska Sabina , Bednarski Marek , Siwek Agata , Satała Grzegorz , Czarnota Kinga , Handzlik Jadwiga , Kieć-Kononowicz Katarzyna
Published: November 2021

Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity. The newly synthesized compounds were tested in the radioligand binding assay and the intrinsic activity was evaluated for the selected derivatives. The computer-aided SAR analysis enabled us to answer questions about the influence of particular structural fragments on selective vs. multifunctional activity. As a result of the performed investigations, there were two leading structures: (a) compound 12 with multifunctional adrenergic-serotonin activity, which is a promising candidate to be an effective anxiolytic agent; (b) compound 14 with high α1A/α1D affinity and selectivity towards α1B, which is recommended due to the elimination of probable cardiotoxic effect. The structural conclusions of this work provide significant support for future lead optimization in order to achieve the desired pharmacodynamic profile in searching for new CNS-modulating agents.
Enzymatic Methods for Salivary Biomarkers Detection: Overview and Current Challenges
Authors: Ornelas-González Alonso , Ortiz-Martínez Margarita , González-González Mirna , Rito-Palomares Marco
Published: November 2021

Early detection is a key factor in patient fate. Currently, multiple biomolecules have been recognized as biomarkers. Nevertheless, their identification is only the starting line on the way to their implementation in disease diagnosis. Although blood is the biofluid par excellence for the quantification of biomarkers, its extraction is uncomfortable and painful for many patients. In this sense, there is a gap in which saliva emerges as a non-invasive and valuable source of information, as it contains many of the biomarkers found in blood. Recent technological advances have made it possible to detect and quantify biomarkers in saliva samples. However, there are opportunity areas in terms of cost and complexity, which could be solved using simpler methodologies such as those based on enzymes. Many reviews have focused on presenting the state-of-the-art in identifying biomarkers in saliva samples. However, just a few of them provide critical analysis of technical elements for biomarker quantification in enzymatic methods for large-scale clinical applications. Thus, this review proposes enzymatic assays as a cost-effective alternative to overcome the limitations of current methods for the quantification of biomarkers in saliva, highlighting the technical and operational considerations necessary for sampling, method development, optimization, and validation.
Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane
Authors: Štefan Leo , Čikoš Ana , Vianello Robert , Đilović Ivica , Matković-Čalogović Dubravka , Dumić Miljenko
Published: November 2021

Spontaneous S-alkylation of methimazole (1) with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1H-imidazole-2-yl)thio]ethane (2), that we have described recently, opened the question about its formation pathway(s). Results of the synthetic, NMR spectroscopic, crystallographic and computational studies suggest that, under given conditions, 2 is obtained by direct attack of 1 on the chloroethyl derivative 2-[(chloroethyl)thio]-1-methyl-1H-imidazole (3), rather than through the isolated stable thiiranium ion isomer, i.e., 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium chloride (4a, orthorhombic, space group Pnma), or in analogy with similar reactions, through postulated, but unproven intermediate thiiranium ion 5. Furthermore, in the reaction with 1, 4a prefers isomerization to the N-chloroethyl derivative, 1-chloroethyl-2,3-dihydro-3-methyl-1H-imidazole-2-thione (7), rather than alkylation to 2, while 7 further reacts with 1 to form 3-methyl-1-[(1-methyl-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8, monoclinic, space group P 21/c). Additionally, during the isomerization of 3, the postulated intermediate thiiranium ion 5 was not detected by chromatographic and spectroscopic methods, nor by trapping with AgBF4. However, trapping resulted in the formation of the silver complex of compound 3, i.e., bis-{2-[(chloroethyl)thio]-1-methyl-1H-imidazole}-silver(I)tetrafluoroborate (6, monoclinic, space group P 21/c), which cyclized upon heating at 80 °C to 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium tetrafluoroborate (4b, monoclinic, space group P 21/c). Finally, we observed thermal isomerization of both 2 and 2,3-dihydro-3-methyl-1-[(1-methyl-1H-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8), into 1,2-bis(2,3-dihydro-3-methyl-1H-imidazole-2-thione-1-yl)ethane (9), which confirmed their structures.
Three New Phthalide Glycosides from the Rhizomes of Cnidium officinale and Their Recovery Effect on Damaged Otic Hair Cells in Zebrafish
Authors: Kim Hyoung-Geun , Oh Seon Min , Kim Na Woo , Shim Ji Heon , Nam Youn Hee , Nguyen Trong Nguyen , Lee Min-Ho , Lee Dae Young , Kang Tong Ho , Baek Nam-In
Published: November 2021

The extract from Cnidium officinale rhizomes was shown in a prior experiment to markedly recover otic hair cells in zebrafish damaged by neomycin. The current study was brought about to identify the principal metabolite. Column chromatography using octadecyl SiO2 and SiO2 was performed to isolate the major metabolites from the active fraction. The chemical structures were resolved on the basis of spectroscopic data, including NMR, IR, MS, and circular dichroism (CD) data. The isolated phthalide glycosides were assessed for their recovery effect on damaged otic hair cells in neomycin-treated zebrafish. Three new phthalide glycosides were isolated, and their chemical structures, including stereochemical characteristics, were determined. Two glycosides (0.1 μM) showed a recovery effect (p < 0.01) on otic hair cells in zebrafish affected by neomycin ototoxicity. Repeated column chromatography led to the isolation of three new phthalide glycosides, named ligusticosides C (1), D (2), and E (3). Ligusticoside C and ligusticoside E recovered damaged otic hair cells in zebrafish.
Being Uncertain in Chromatographic Calibration—Some Unobvious Details in Experimental Design
Authors: Komsta Łukasz , Wicha-Komsta Katarzyna , Kocki Tomasz
Published: November 2021

This is an introductory tutorial and review about the uncertainty problem in chromatographic calibration. It emphasizes some unobvious, but important details influencing errors in the calibration curve estimation, uncertainty in prediction, as well as the connections and dependences between them, all from various perspectives of uncertainty measurement. Nonuniform D-optimal designs coming from Fedorov theorem are computed and presented. As an example, all possible designs of 24 calibration samples (3–8, 4–6, 6–4, 8–3 and 12–2, both uniform and D-optimal) are compared in context of many optimality criteria. It can be concluded that there are only two independent (orthogonal, but slightly complex) trends in optimality of these designs. The conclusions are important, as the uniform designs with many concentrations are not the best choices, contrary to some intuitive perception. Nonuniform designs are visibly better alternative in most calibration cases.
The Antileukemic Effect of Xestoquinone, A Marine-Derived Polycyclic Quinone-Type Metabolite, Is Mediated through ROS-Induced Inhibition of HSP-90
Authors: Wang Kuan-Chih , Lu Mei-Chin , Hsu Kai-Cheng , El-Shazly Mohamed , Shih Shou-Ping , Lien Ssu-Ting , Kuo Fu-Wen , Yang Shyh-Chyun , Chen Chun-Lin , Yang Yu-Chen S. H.
Published: November 2021

Xestoquinone is a polycyclic quinone-type metabolite with a reported antitumor effect. We tested the cytotoxic activity of xestoquinone on a series of hematological cancer cell lines. The antileukemic effect of xestoquinone was evaluated in vitro and in vivo. This marine metabolite suppressed the proliferation of Molt-4, K562, and Sup-T1 cells with IC50 values of 2.95 ± 0.21, 6.22 ± 0.21, and 8.58 ± 0.60 µM, respectively, as demonstrated by MTT assay. In the cell-free system, it inhibited the activity of topoisomerase I (Topo I) and II (Topo II) by 50% after treatment with 0.235 and 0.094 μM, respectively. The flow cytometric analysis indicated that the cytotoxic effect of xestoquinone was mediated through the induction of multiple apoptotic pathways in Molt-4 cells. The pretreatment of Molt-4 cells with N-acetyl cysteine (NAC) diminished the disruption of the mitochondrial membrane potential (MMP) and apoptosis, as well as retaining the expression of both Topo I and II. In the nude mice xenograft model, the administration of xestoquinone (1 μg/g) significantly attenuated tumor growth by 31.2% compared with the solvent control. Molecular docking, Western blotting, and thermal shift assay verified the catalytic inhibitory activity of xestoquinone by high binding affinity to HSP-90 and Topo I/II. Our findings indicated that xestoquinone targeted leukemia cancer cells through multiple pathways, suggesting its potential application as an antileukemic drug lead.