bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty Acid Amide Hydrolase (FAAH) Inhibition Plays a Key Role in Counteracting Acute Lung Injury
Authors: Genovese Tiziana , Duranti Andrea , D’Amico Ramona , Fusco Roberta , Impellizzeri Daniela , Peritore Alessio Filippo , Crupi Rosalia , Gugliandolo Enrico , Cuzzocrea Salvatore , Di Paola Rosanna , Siracusa Rosalba , Cordaro Marika
Published: March 2022

Acute lung injury (ALI) is a group of lung illnesses characterized by severe inflammation, with no treatment. The fatty acid amide hydrolase (FAAH) enzyme is an integral membrane protein responsible for the hydrolysis of the main endocannabinoids, such as anandamide (AEA). In pre-clinical pain and inflammation models, increasing the endogenous levels of AEA and other bioactive fatty acid amides (FAAs) via genetic deletion or the pharmacological inhibition of FAAH produces many analgesic benefits in several different experimental models. To date, nobody has investigated the role of FAAH inhibition on an ALI mouse model. Mice were subjected to a carrageenan injection and treated orally 1 h after with the FAAH inhibitor URB878 dissolved in a vehicle consisting of 10% PEG-400, 10% Tween-80 and 80% saline at different doses: The inhibition of FAAH activity was able to counteract not only the CAR-induced histological alteration, but also the cascade of related inflammatory events. URB878 clears the way for further studies based on FAAH inhibition in acute lung pathologies.
Addressing the Needs of the Rapidly Aging Society through the Development of Multifunctional Bioactive Coatings for Orthopedic Applications
Authors: Mastnak Tinkara , Maver Uroš , Finšgar Matjaž
Published: March 2022

The unprecedented aging of the world’s population will boost the need for orthopedic implants and expose their current limitations to a greater extent due to the medical complexity of elderly patients and longer indwelling times of the implanted materials. Biocompatible metals with multifunctional bioactive coatings promise to provide the means for the controlled and tailorable release of different medications for patient-specific treatment while prolonging the material’s lifespan and thus improving the surgical outcome. The objective of this work is to provide a review of several groups of biocompatible materials that might be utilized as constituents for the development of multifunctional bioactive coatings on metal materials with a focus on antimicrobial, pain-relieving, and anticoagulant properties. Moreover, the review presents a summary of medications used in clinical settings, the disadvantages of the commercially available products, and insight into the latest development strategies. For a more successful translation of such research into clinical practice, extensive knowledge of the chemical interactions between the components and a detailed understanding of the properties and mechanisms of biological matter are required. Moreover, the cost-efficiency of the surface treatment should be considered in the development process.
Rapid Discrimination of Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis Using Machine Learning on Infrared Spectra of Sera
Authors: El Khoury Youssef , Gebelin Marie , de Sèze Jérôme , Patte-Mensah Christine , Marcou Gilles , Varnek Alexandre , Mensah-Nyagan Ayikoé-Guy , Hellwig Petra , Collongues Nicolas
Published: March 2022

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are both autoimmune inflammatory and demyelinating diseases of the central nervous system. NMOSD is a highly disabling disease and rapid introduction of the appropriate treatment at the acute phase is crucial to prevent sequelae. Specific criteria were established in 2015 and provide keys to distinguish NMOSD and MS. One of the most reliable criteria for NMOSD diagnosis is detection in patient’s serum of an antibody that attacks the water channel aquaporin-4 (AQP-4). Another target in NMOSD is myelin oligodendrocyte glycoprotein (MOG), delineating a new spectrum of diseases called MOG-associated diseases. Lastly, patients with NMOSD can be negative for both AQP-4 and MOG antibodies. At disease onset, NMOSD symptoms are very similar to MS symptoms from a clinical and radiological perspective. Thus, at first episode, given the urgency of starting the anti-inflammatory treatment, there is an unmet need to differentiate NMOSD subtypes from MS. Here, we used Fourier transform infrared spectroscopy in combination with a machine learning algorithm with the aim of distinguishing the infrared signatures of sera of a first episode of NMOSD from those of a first episode of relapsing-remitting MS, as well as from those of healthy subjects and patients with chronic inflammatory demyelinating polyneuropathy. Our results showed that NMOSD patients were distinguished from MS patients and healthy subjects with a sensitivity of 100% and a specificity of 100%. We also discuss the distinction between the different NMOSD serostatuses. The coupling of infrared spectroscopy of sera to machine learning is a promising cost-effective, rapid and reliable differential diagnosis tool capable of helping to gain valuable time in patients’ treatment.
Molecular Research in Multiple Sclerosis
Authors: Fucito Maurine , Pieragostino Damiana
Published: March 2022

The Special Issue, “Molecular Research in Multiple Sclerosis”, provides a better comprehension of the disease and establishes possible new biomarkers to ensure better care of MS patients in the future [...]
Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors
Authors: Zaragoza-Huesca David , Martínez-Cortés Carlos , Banegas-Luna Antonio Jesús , Pérez-Garrido Alfonso , Vegara-Meseguer Josefina María , Peñas-Martínez Julia , Rodenas Maria Carmen , Espín Salvador , Pérez-Sánchez Horacio , Martínez-Martínez Irene
Published: March 2022

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.
Sodium Nitroprusside-Induced Activation of Vascular Smooth Muscle BK Channels Is Mediated by PKG Rather Than by a Direct Interaction with NO
Authors: Gagov Hristo , Gribkova Irina , Serebryakov Vladimir , Schubert Rudolf
Published: March 2022

Nitric oxide (NO) is a powerful vasodilator in different vascular beds and NO-donors are widely used in clinical practice. Early data suggested that NO and NO-donors activate vascular smooth muscle high-conductance, calcium-activated potassium channels (BK channels). There exist two hypotheses explaining the effect of NO and NO-donors on BK channels—one stating that protein kinase G (PKG) mediates the effect of NO, and the other one stating that NO acts directly on the channel. Thus, the degree of contribution of PKG to the NO-induced activation of the BK channel is still not completely clear. This study tested the hypothesis that the sodium nitroprusside (SNP)-induced activation of vascular smooth muscle BK channels is fully mediated by PKG. This hypothesis was investigated using the patch-clamp technique and freshly isolated smooth muscle cells from rat tail artery. In whole-cell experiments, SNP considerably increased the outward current compared with the addition of the bath solution. SNP did not alter the current in the presence of iberiotoxin, the specific blocker of BK channels, during co-application with hydroxocobalamin, an NO-scavenger, and in the presence of Rp-8-Br-PET-cGMPS, the specific PKG-inhibitor. In inside-out patches, the activity of BK channels was increased by SNP, SNAP, and DEA-NO. However, these effects did not differ from the effect of the application of drug-free bath solution. Furthermore, a similar increase in single BK channel activity was induced by Rp-8-Br-PET-cGMPS, Rp-8-Br-PET-cGMPS together with SNP, hydroxocobalamin, and hydroxocobalamin together with SNP or DEA-NO. Finally, the activity of excised BK channels did not change in the absence of any application but was considerably increased by PKG compared with the addition of drug-free bath solution. These results suggest that NO released from NO-donors stimulates the BK current only through activation of PKG.
ICT Use, Digital Skills and Students’ Academic Performance: Exploring the Digital Divide
Authors: Ben Youssef Adel , Dahmani Mounir , Ragni Ludovic
Published: March 2022

Information and communication technologies (ICTs) are an integral part of our environment, and their uses vary across generations and among individuals. Today’s student population is made up of “digital natives” who have grown up under the ubiquitous influence of digital technologies, and for whom the use of ICT is common and whose daily activities are structured around media use. The aim of this study is to examine the impact of ICT use and digital skills on students’ academic performance and to explore the digital divide in France. Data were collected through face-to-face questionnaires administered to 1323 students enrolled in three French universities. Principal component analysis, a non-hierarchical k-means clustering approach and multilevel ordered logistic regression were used for data analysis and provide four main findings: first, poor investment in ICT affects students’ results; second, the ICT training offered by universities has little impact on students’ results; third, student performance improves with the innovative and collaborative use of ICTs; fourth, the acquisition of digital skills increases students’ academic performance. The results show that the digital divide still exists, and this raises questions about the effectiveness of education policies in France. They suggest also that organizational change in universities is essential to enable an exploitation of ICT.
Underwater Image Restoration via DCP and Yin–Yang Pair Optimization
Authors: Yu Kun , Cheng Yufeng , Li Longfei , Zhang Kaihua , Liu Yanlei , Liu Yufang
Published: March 2022

Underwater image restoration is a challenging problem because light is attenuated by absorption and scattering in water, which can degrade the underwater image. To restore the underwater image and improve its contrast and color saturation, a novel algorithm based on the underwater dark channel prior is proposed in this paper. First of all, in order to reconstruct the transmission maps of the underwater image, the transmission maps of the blue and green channels are optimized by the proposed first-order and second-order total variational regularization. Then, an adaptive model is proposed to improve the first-order and second-order total variation. Finally, to solve the problem of the excessive attenuation of the red channel, the transmission map of the red channel is compensated by Yin–Yang pair optimization. The simulation results show that the proposed restored algorithm outperforms other approaches in terms of the visual effects, average gradient, spatial frequency, percentage of saturated pixels, underwater color image quality evaluation and evaluation metric.
Morphological and Phylogenetic Evidence Reveal Five New Telamonioid Species of Cortinarius (Agaricales) from East Asia
Authors: Xie Meng-Le , Phukhamsakda Chayanard , Wei Tie-Zheng , Li Ji-Peng , Wang Ke , Wang Yang , Ji Rui-Qing , Li Yu
Published: March 2022

Five new Cortinarius species, C. neobalaustinus, C. pseudocamphoratus, C. subnymphatus, C. wuliangshanensis and C. yanjiensis spp. nov., are proposed based on a combination of morphological and molecular evidence. Cortinarius neobalaustinus is characterized by a very weakly hygrophanous and yellowish-brown to brown pileus and small and weakly verrucose basidiospores. Cortinarius pseudocamphoratus can be characterized by a viscid pileus, a strongly unpleasant smell, amygdaloid to somewhat ellipsoid basidiospores and lageniform to subfusiform cheilocystidia. Cortinarius subnymphatus is identified by a strongly hygrophanous pileus that is reddish-brown with a black-brown umbo, a yellowish universal veil and ellipsoid to subamygdaloid basidiospores. Cortinarius wuliangshanensis is characterized by a moderately to strongly hygrophanous, translucently striated and yellowish to reddish-brown pileus and rather weakly and moderately verrucose basidiospores. Cortinarius yanjiensis is distinguished by a weakly to moderately hygrophanous and yellowish to brown pileus and moderately to rather strongly verrucose basidiospores. The phylogenetic analyses were performed with maximum likelihood and Bayesian inference methods based on the data set of nuc rDNA ITS1-5.8S-ITS2 (ITS), D1–D2 domains of nuc 28S rDNA (28S) and RNA polymerase II second largest subunit (rpb2), and the results show that C. neobalaustinus, C. wulianghsanensis and C. yanjiensis cluster in sect. Illumini, C. pseudocamporatus belongs to sect. Camphorati and C. subnymphatus belongs to sect. Laeti. In addition, a study of basidiospores under field emission scanning electron microscopy (FESEM) was conducted. An identification key for the five new species and related species from China is also provided.
A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021
Authors: Guemas Emilie , Cassaing Sophie , Malavaud Sandra , Fillaux Judith , Chauvin Pamela , Lelièvre Lucie , Ruiz Stéphanie , Riu Béatrice , Berry Antoine , Iriart Xavier
Published: March 2022

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU.
Stolen Wages, Corruption, and Selective Application of the Law: Is APUNCAC a Solution?
Authors: Notley Anna , Hodge Bob
Published: March 2022

APUNCAC is a draft international convention designed to address systemic corruption, strengthening UNCAC’s provisions and adding mechanisms to make it more effective. ‘Corruption’ includes public officials abusing their powers. This article addresses an especially insidious form: when laws are created and applied to deny equal protection under the law. Ruling elites control the executive and parliament, to pass laws that selectively target and disadvantage a segment of the population. Our empirical data comes from a historical case, massive government-sanctioned wage theft from Western Australian Aboriginal workers between 1901 and 1972. We use these data to analyse how this kind of corruption works in practice, to evaluate APUNCAC’s measures and strategies, to see what specific measures might be used or modified, and where APUNCAC might need supplementing. We argue that Article 4(3) could have a major impact, especially supported by other Articles and processes, such as dedicated independent courts and strategic engagement with local courts. We evaluate two scenarios: The first scenario is prospective, assuming that APUNCAC is adopted. We evaluate the possible impact of APUNCAC in deterring future corruption involving selective application of the law. The second scenario is retrospective. We evaluate the possible support that APUNCAC might provide regarding court actions that seek redress for potential litigants, such as WA Aboriginal people who were injured in the past.
Shear Bond Strength and Bracket Base Morphology of New and Rebonded Orthodontic Ceramic Brackets
Authors: Urichianu Mihai , Makowka Steven , Covell David , Warunek Stephen , Al-Jewair Thikriat
Published: March 2022

The objectives of this study were to (1) to evaluate the shear bond strength (SBS) of two ceramic brackets when new and when rebonded following various bracket base conditioning methods, and (2) to determine bond failure mode relative to bracket base morphology. 100 Symetri ClearTM (SC) and 100 Radiance Plus® (RP) ceramic brackets were bonded to bovine incisors and divided into five groups: one group served as controls and four had brackets rebonded following conditioning by: no surface treatment, sealant, sandblasting, and flame then steam. SBS, adhesive remnant index, and bracket base morphology were evaluated. SBS showed no statistical difference between new and rebonded with no surface treatment or sealant (SC brackets) and with sealant or flame and steam (RP brackets). When comparing SC to RP, SBS was higher with SC, no surface treatment, and sandblasted groups. All groups had varying amounts of adhesive left on the tooth, with the sandblasted group having the most. SEM analysis showed that sandblasting damaged the retention features of bracket bases. In conclusion, when rebonded, the SBS of SC brackets that had no surface treatment and both SC and RP brackets that had sealant showed no significant differences to new brackets. Sandblasting damaged the retention features of SC and RP bracket bases, resulting in low SBS.
Properties of Fe–Si Alloy Anode for Lithium-Ion Battery Synthesized Using Mechanical Milling
Authors: Lee Kikang , Jeong Jejun , Chu Yeoneyi , Kim Jongbeom , Oh Kyuhwan , Moon Jeongtak
Published: March 2022

Silicon (Si)-based anode materials can increase the energy density of lithium (Li)-ion batteries owing to the high weight and volume capacity of Si. However, their electrochemical properties rapidly deteriorate due to large volume changes in the electrode resulting from repeated charging and discharging. In this study, we manufactured structurally stable Fe–Si alloy powders by performing high-energy milling for up to 24 h through the reduction of the Si phase size and the formation of the α-FeSi2 phase. The cause behind the deterioration of the electrochemical properties of the Fe–Si alloy powder produced by over-milling (milling for an increased time) was investigated. The 12 h milled Fe–Si alloy powder showed the best electrochemical properties. Through the microstructural analysis of the Fe–Si alloy powders after the evaluation of half/full coin cells, powder resistance tests, and charge/discharge cycles, it was found that this was due to the low electrical conductivity and durability of β-FeSi2. The findings provide insight into the possible improvements in battery performance through the commercialization of Fe–Si alloy powders produced by over-milling in a mechanical alloying process.
The Relationship between Poisson’s Ratio Index and Deformation Behavior of Asphalt Mixtures Tested through an Optical Fiber Bragg Grating Strain Sensor
Authors: Liu Xu , Zhang Mo , Liu Wanqiu
Published: March 2022

Flow-rutting is the main distress leading asphalt pavement to undergo premature maintenance, and is produced by the rapid accumulation of shear deformation in asphalt layers under high temperature and heavy loads. The excessive permanent deformation of the asphalt mixture at high temperature is related to the decrease of the material’s stability during the temperature increase and an unfavorable stress state, e.g., low confining pressure and high shear stress, which eventually leads to significant nonlinear viscoplastic behavior. In this research, dynamic modulus tests and repeated loading tests were carried out at 35 °C and 50 °C to analyze the deformation response of materials under a strain amplitude of <200 με and 400~500 μεs, respectively. Based on the in-lab repeated loading tests, the total deformation of the asphalt mixture in each loading and rest cycle was divided into three parts, being elastic, viscoelastic, and viscoplastic strain, and the measurement of the axial and lateral strain of cylindrical samples was realized with the aid of optical fiber Bragg grating strain sensors. It was found that the experimental index of the ratio between lateral strain and longitudinal strain (RLSLS), derived, but distinguished, from Poisson’s ratio defined limited in elastic strain, can characterize the deformation in viscoelastic and viscoplastic behaviors of the mixes. Furthermore, the indices of dynamic modulus, phase angle, complex Poisson’s ratio, stiffness, and creep rate of four types of mixes containing different volcanic ash fillers and asphalt binders at 35 °C and 50 °C were systematically analyzed by the jointed experiments of modified dynamic modulus tests and repeated loading tests, and their consistent trending to the RLSLS index was obtained.
Growth of Anodic Layers on 304L Stainless Steel Using Fluoride Free Electrolytes and Their Electrochemical Behavior in Chloride Solution
Authors: Domínguez-Jaimes Laura Patricia , Arenas María A. , Conde Ana , Escobar-Morales Beatriz , Álvarez-Méndez Anabel , Hernández-López Juan Manuel
Published: March 2022

Anodic layers have been grown on 304L stainless steel (304L SS) using two kinds of fluoride-free organic electrolytes. The replacement of NH4F for NaAlO2 or Na2SiO3 in the glycerol solution and the influence of the H2O concentration have been examined. The obtained anodic layers were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and potentiodynamic polarization tests. Here, it was found that, although the anodic layers fabricated within the NaAlO2-electrolyte and high H2O concentrations presented limited adherence to the substrate, the anodizing in the Na2SiO3-electrolyte and low H2O concentrations allowed the growth oxide layers, and even a type of ordered morphology was observed. Furthermore, the electrochemical tests in chloride solution determined low chemical stability and active behavior of oxide layers grown in NaAlO2-electrolyte. In contrast, the corrosion resistance was improved approximately one order of magnitude compared to the non-anodized 304L SS substrate for the anodizing treatment in glycerol, 0.05 M Na2SiO3, and 1.7 vol% H2O at 20 mA/cm2 for 6 min. Thus, this anodizing condition offers insight into the sustainable growth of oxide layers with potential anti-corrosion properties.
Determination and Verification of GISSMO Fracture Properties of Bolts Used in Radioactive Waste Transport Containers
Authors: Gu Bonjoon , Lim Jongmin , Hong Seokmoo
Published: March 2022

Transport containers for radioactive materials should withstand drop tests according to the regulations. In order to prevent a loss or dispersal of the internal radioactive materials in the drop tests, a tightening of the lid of the transport container should be maintained. The opening of the lid, due to the drop impact, might cause the dispersion of internal contents or a loss of shielding performance. Thus, it is crucial to predict damage to the fastening bolt and its fracture. In this study, the damage parameters of the fastening bolt were acquired, and its fracture was predicted using the generalized incremental stress state-dependent damage model (GISSMO), a phenomenological damage model. Since the dedicated transport container is large and heavy, various jigs that can simulate the fall of the container were designed, and the accuracy of fracture prediction was verified. Digital image correlation (DIC) was introduced for the accurate measurement of the displacement, and load–displacement data for tensile, shear, and combined loads were successfully acquired. Finally, the load–displacement curve of the finite element analysis (FEA) with GISSMO until the point of the bolt fracture was compared with the curve obtained from the experiment, where a good agreement was observed.
Hemp Fibre Properties and Processing Target Textile: A Review
Authors: Zimniewska Malgorzata
Published: March 2022

Over the last several decades, Cannabis sativa L. has become one of the most fashionable plants. To use the hemp potential for the development of a sustainable textile bio-product sector, it is necessary to learn about the effect of the processes creating hemp’s value chain on fibre properties. This review presents a multi-perspective approach to industrial hemp as a resource delivering textile fibres. This article extensively explores the current development of hemp fibre processes including methods of fibre extraction and processing and comprehensive fibre characteristics to indicate the challenges and opportunities regarding Cannabis sativa L. Presented statistics prove the increasing interest worldwide in hemp raw material and hemp-based bio-products. This article discusses the most relevant findings in terms of the effect of the retting processes on the composition of chemical fibres resulting in specific fibre properties. Methods of fibre extraction include dew retting, water retting, osmotic degumming, enzymatic retting, steam explosion and mechanical decortication to decompose pectin, lignin and hemicellulose to remove them from the stem with varying efficiency. This determines further processes and proves the diversity of ways to produce yarn by employing different spinning systems such as linen spinning, cotton and wool spinning technology with or without the use of the decortication process. The aim of this study is to provide knowledge for better understanding of the textile aspects of hemp fibres and their relationship to applied technological processes.
Energy Relaxation and Electron–Phonon Coupling in Laser-Excited Metals
Authors: Zhang Jia , Qin Rui , Zhu Wenjun , Vorberger Jan
Published: March 2022

The rate of energy transfer between electrons and phonons is investigated by a first-principles framework for electron temperatures up to Te = 50,000 K while considering the lattice at ground state. Two typical but differently complex metals are investigated: aluminum and copper. In order to reasonably take the electronic excitation effect into account, we adopt finite temperature density functional theory and linear response to determine the electron temperature-dependent Eliashberg function and electron density of states. Of the three branch-dependent electron–phonon coupling strengths, the longitudinal acoustic mode plays a dominant role in the electron–phonon coupling for aluminum for all temperatures considered here, but for copper it only dominates above an electron temperature of Te = 40,000 K. The second moment of the Eliashberg function and the electron phonon coupling constant at room temperature Te=315 K show good agreement with other results. For increasing electron temperatures, we show the limits of the T=0 approximation for the Eliashberg function. Our present work provides a rich perspective on the phonon dynamics and this will help to improve insight into the underlying mechanism of energy flow in ultra-fast laser–metal interaction.
Study of Wear Phenomenon of a Dental Milling Cutter by Statistical–Mathematical Modeling Based on the Experimental Results
Authors: Ilie Filip , Saracin Ioan Alexandru , Voicu Gheorghe
Published: March 2022

The wear phenomenon of a dental milling cutter is studied based on experimental results and data and validated by statistical–mathematical modeling. The results of the statistical–mathematical modeling by the interpolation of the experimental results (data) regarding the wear of the dental milling cutter analyzed and obtained in the work process are presented in this paper. These results (data) are important because they lead to polynomial functions which by interpolation approximate very well the dependent parameter, specifically the wear process (mass lost due to dental milling cutter wear, mw), considered in the experimental program. The polynomial interpolation functions are valid, only during the experimental testing range of the dental milling cutter, to describe the wear phenomenon; the extrapolations do not lead to satisfactory results. However, by using a controlled interpolation function with an exponential component, the extrapolation of the results is possible. Therefore, the purpose of this paper is the statistical–mathematical modeling by the interpolation of the experimental results of the mass lost due to dental milling cutter wear, mw, using the deterministic differential model for the work process of it. Thus, interesting conclusions can be drawn relating to the phenomenon. In support of these statements come the results of the statistical–mathematical modeling by the interpolation of the experimental data obtained in the work process of the dental milling cutters, leading to practical applications, such as the extension of the life of dental milling cutter, useful even for its operation optimization; determination of possible criteria for replacing the worn dental milling cutters; the extension of the life of the materials from which dental milling cutters are built; or the provision of ideas for constructive solutions. Based on the modeling results by interpolation, it was found that the dental milling cutter during the milling operation works with high efficiency (mass loss due to wear is very reduced) in the first 11 h of operation, i.e., about a 10% increase in lifetime. After 11 h of operation, mass loss due to wear of the dental milling cutter increases relatively exponentially; thus, it is recommended that, in the normal way, the dental milling cutter be replaced with a new one to ensure high standards of materials processing.
Study of Structure–Activity Relationships of the Marine Alkaloid Fascaplysin and Its Derivatives as Potent Anticancer Agents
Authors: Zhidkov Maxim E. , Kaune Moritz , Kantemirov Alexey V. , Smirnova Polina A. , Spirin Pavel V. , Sidorova Maria A. , Stadnik Sergey A. , Shyrokova Elena Y. , Kaluzhny Dmitry N. , Tryapkin Oleg A. , Busenbender Tobias , Hauschild Jessica , Rohlfing Tina , Prassolov Vladimir S. , Bokemeyer Carsten , Graefen Markus , von Amsberg Gunhild , Dyshlovoy Sergey A.
Published: March 2022

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.
Cardio-Protective Properties and Health Benefits of Fish Lipid Bioactives; The Effects of Thermal Processing
Authors: Tsoupras Alexandros , Brummell Chloe , Kealy Ciara , Vitkaitis Karolis , Redfern Shane , Zabetakis Ioannis
Published: March 2022

The beneficial effects of fish-derived lipid bioactives have come to prominence over the last few decades, especially for their utilization in fish oils, supplements, and nutraceuticals. Omega-3 (n-3) polyunsaturated fatty acids (PUFA), lipid vitamins, carotenoids, and polar lipid bioactives from fish have shown to possess a vast range of beneficial effects against a multitude of chronic disorders and especially against inflammation-and cardiovascular disorders (CVD). The observed cardio-protective effects and health benefits are believed to be attributed to the synergy of these fish-derived lipid bioactives. Within the present article the recent findings in the literature on the lipid content of the mainly consumed fish species, their bio-functionality, and cardio-protective benefits is thoroughly reviewed. Moreover, the recovery and valorization of such lipid bioactives from fish by-products and fishing by-catch, in order to reduce waste, while developing useful products containing cardio-protective lipids from the leftover materials of fisheries and aquaculture industries, are also of industrial and environmental interest. Emphasis is also given to the effects of heat treatments during fish processing on the structures and bio-functionality of these marine lipid bioactives, based on the paradigm of different cooking methodologies and thermal processing, while the compounds produced during such treatment(s) with detrimental changes in the fish lipid profile, which can reduce its cardio-protective efficacy, are also reviewed. Novel green extraction technologies and low temperature processing and cooking of fish and fishery by-products are needed to reduce these undesirable effects in a sustainable and environmentally friendly way.
Effect of Two Different Rehabilitation Approaches on Pulmonary Functional Tests, Neuromuscular Functions and Quality of Life in Juvenile Myasthenia Gravis: A Randomized Controlled Trial Study
Authors: Mohamed Rasha A. , Mohamed El Sayed H. , Basiouny Mohamed A. , Hamoda Ibrahim M. , Hanoura El Sayed M. , Elhenedi Elbadawy I. , Sherief Abd El Aziz A.
Published: March 2022

Background and Objectives: Children with juvenile myasthenia gravis have a variety of symptoms, ranging from isolated intermittent ocular complaints to overall muscle weakness with or without respiratory insufficiency. This study aimed to investigate the efficacy of a specialized physical therapy with or without partial body weight supported treadmill training on pulmonary functional tests, neuromuscular functions, and quality of life. Materials and Methods: Thirty children, ranging in age from 13 to 16 years, were distributed randomly into two study groups (A or B). Both groups underwent a designed physical therapy program. In addition, group A underwent the partial body weight supported treadmill training. The treatment was conducted three times a week for 12 weeks successively. Pulmonary functional tests (FVC, FEV1, PEFR, and MVV), neuromuscular function tests (compound motor action potential, isometric muscle force of biceps brachii and rectus femoris, balance, walking endurance, and fatigue), and quality of life were measured before and after 12 successive weeks. Results: A significant improvement in all investigated variables were recorded in both groups in favor of group A. Conclusions: Both a specialized physical therapy and partial body weight supported treadmill training are effective in terms of enhancing pulmonary functional tests, neuromuscular functions, and quality of life. Partial body weight supported treadmill training is an excellent adjunctive to the physical therapy program.
A Novel Methodology to Obtain the Mechanical Properties of Membranes by Means of Dynamic Tests
Authors: Lima-Rodriguez Antonia , Garcia-Manrique Jose , Dong Wei , Gonzalez-Herrera Antonio
Published: March 2022

A new, non-destructive methodology is proposed in this work in order to determine the mechanical properties of membrane using vibro-acoustic tests. This procedure is based on the dynamic analysis of the behavior of the membrane. When the membrane is subjected to a sound excitation it responds by vibrating based on its modal characteristics and this modal parameter is directly related to its mechanical properties. The paper is structured in two parts. First, the theoretical bases of the test are presented. The interaction between the sound waves and the membrane (mechano-acoustic coupling) is complex and requires meticulous study. It was broadly studied by means of numerical simulations. A summary of this study is shown. Aspects, such as the position of the sound source, the measuring points, the dimensions of the membrane, the frequency range, and the magnitudes to be measured, among others, were evaluated. The validity of modal analysis curve-fitting techniques to extract the modal parameter from the data measures was also explored. In the second part, an experimental test was performed to evaluate the validity of the method. A membrane of the same material with three different diameters was measured with the aim of estimating the value of the Young’s modulus. The procedure was applied and satisfactory results were obtained. Additionally, the experiment shed light on aspects that must be taken account in future experiments.
The Intestinal Barrier—Shielding the Body from Nano- and Microparticles in Our Diet
Authors: Schwarzfischer Marlene , Rogler Gerhard
Published: March 2022

Nano- and microparticles are an implicit part of the human diet. They are unknowingly ingested with our food that contains them as additives or pollutants. However, their impact on human health is not yet understood and controversially discussed. The intestinal epithelial barrier shields our body against exogenous influences, such as commensal bacteria, pathogens, and body-foreign particles and, therefore, protects our body integrity. Breakdown of the intestinal epithelial barrier and aberrant immune responses are key events in the pathogenesis of inflammatory bowel disease (IBD). Epithelial lesions might enable systemic translocation of nano- and microparticles into the system, eventually triggering an excessive immune response. Thus, IBD patients could be particularly vulnerable to adverse health effects caused by the ingestion of synthetic particles with food. The food-additive titanium dioxide (TiO2) serves as a coloring agent in food products and is omnipresent in the Western diet. TiO2 nanoparticles exacerbate intestinal inflammation by activation of innate and adaptive immune response. Because of serious safety concerns, the use of TiO2 as a food additive was recently banned from food production within the European Union. Due to environmental pollution, plastic has entered the human food chain, and plastic microparticles have been evidenced in the drinking water and comestible goods. The impact of plastic ingestion and its resulting consequences on human health is currently the subject of intense research. Focusing on TiO2 and plastic particles in the human diet and their impact on epithelial integrity, gut homeostasis, and intestinal inflammation, this review is addressing contemporary hot topics which are currently attracting a lot of public attention.
Method for Identifying and Forecasting Mining-Induced Earthquakes Based on Spatiotemporal Characteristics of Microseismic Activities in Fankou Lead/Zinc Mine
Authors: Li Yanyan , Deng Hongwei , Wen Lei , Qin Yaguang , Xu Xiao
Published: March 2022

The risks associated with underground mining at Fankou Lead/Zinc Mine in South China are growing due to the large-scale mining activities there. To recognize mining-induced earthquakes and assess the risk per mining level, a microseismic monitoring system, which is used to record microseismic events, is installed at multiple mining levels in Fankou Lead/Zinc Mine. The purpose of this study is to identify mining-induced earthquakes and to evaluate the risk per mining level by analyzing the spatiotemporal characteristics of microseismic activities in the Fankou Lead/Zinc Mine. In this study, the Gutenberg-Richter (G-R) relationship is applied to compute the b-value, which is used to obtain the maximum magnitude (M (max)) of microseismic event that probably occurs at each mining level. Then, the evaluation of the recurrence period for M (max) and the probability of the microseismic event with the magnitude M (max) is carried out and the M (max) at each mining level is determined based on the recording period of microseismic events. The results show that factors such as the maximum rock vibration velocity, source parameters, displacement, microseismic waveform and energy ratio (ES/EP) can be used to distinguish whether a recorded microseismic event is mining-induced earthquake. Additionally, we propose a method to assess the possibility of mining-induced earthquake at each mining level based on M (max) and predict the recurrence time of microseismic event with the magnitude M (max). The of two years results of microseismic events monitoring demonstrate that the current study is promising for identifying mining-induced earthquakes, assessing the risk of mining-induced earthquakes, predicting the potential maximum microseismic event in a region and estimating its recurrence period and its probability in the Fankou Lead/Zinc Mine.
Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy
Authors: Maiti Priyanka , Sharma Priyanka , Nand Mahesha , Bhatt Indra D. , Ramakrishnan Muthannan Andavar , Mathpal Shalini , Joshi Tushar , Pant Ragini , Mahmud Shafi , Simal-Gandara Jesus , Alshehri Sultan , Ghoneim Mohammed M. , Alruwaily Maha , Awadh Ahmed Abdullah Al , Alshahrani Mohammed Merae , Chandra Subhash
Published: March 2022

Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski’s rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (−)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.
Impact of the R292K Mutation on Influenza A (H7N9) Virus Resistance towards Peramivir: A Molecular Dynamics Perspective
Authors: Mtambo Sphamandla E. , Ugbaja Samuel C. , Kumalo Hezekiel M.
Published: March 2022

In March 2013, a novel avian influenza A (H7N9) virus emerged in China. By March 2021, it had infected more than 1500 people, raising concerns regarding its epidemic potential. Similar to the highly pathogenic H5N1 virus, the H7N9 virus causes severe pneumonia and acute respiratory distress syndrome in most patients. Moreover, genetic analysis showed that this avian H7N9 virus carries human adaptation markers in the hemagglutinin and polymerase basic 2 (PB2) genes associated with cross-species transmissibility. Clinical studies showed that a single mutation, neuraminidase (NA) R292K (N2 numbering), induces resistance to peramivir in the highly pathogenic H7N9 influenza A viruses. Therefore, to evaluate the risk for human public health and understand the possible source of drug resistance, we assessed the impact of the NA-R292K mutation on avian H7N9 virus resistance towards peramivir using various molecular dynamics approaches. We observed that the single point mutation led to a distorted peramivir orientation in the enzyme active site which, in turn, perturbed the inhibitor’s binding. The R292K mutation induced a decrease in the interaction among neighboring amino acid residues when compared to its wild-type counterpart, as shown by the high degree of fluctuations in the radius of gyration. MM/GBSA calculations revealed that the mutation caused a decrease in the drug binding affinity by 17.28 kcal/mol when compared to the that for the wild-type enzyme. The mutation caused a distortion of hydrogen bond-mediated interactions with peramivir and increased the accessibility of water molecules around the K292 mutated residue.