bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthocyanin-Related Pigments: Natural Allies for Skin Health Maintenance and Protection
Authors: Correia Patrícia , Araújo Paula , Ribeiro Carolina , Oliveira Hélder , Pereira Ana Rita , Mateus Nuno , de Freitas Victor , Brás Natércia F. , Gameiro Paula , Coelho Patrícia , Bessa Lucinda J. , Oliveira Joana , Fernandes Iva
Published: June 2021

Human skin is commonly described as a particularly dynamic and complex environment, with a physiological balance continuously orchestrated by numerous internal and external factors. Intrinsic aging, exposure to UV radiation and skin pathogens are some of the key players that account for dermatological alterations and ailments. In this regard, this study intended to explore the potential skin-health beneficial properties of a group of molecules belonging to the anthocyanin family: cyanidin- and malvidin-3-O-glucosides and some of their structurally related pigments, resulting in a library of compounds with different structural properties and color hues. The inclusion of both purified compounds and crude extracts provided some insights into their distinctive effects when tested as individual agents or as part of multicomponent mixtures. Overall, most of the compounds were found to reduce biofilm production by S. aureus and P. aeruginosa reference strains, exhibit UV-filter capacity, attenuate the production of reactive oxygen species in human skin keratinocytes and fibroblasts and also showed inhibitory activity of skin-degrading enzymes, in the absence of cytotoxic effects. Carboxypyranocyanidin-3-O-glucoside stood out for its global performance which, combined with its greater structural stability, makes this a particular interesting compound for potential incorporation in topical formulations. Results provide strong evidence of the skin protective effects of these pigments, supporting their further application for cosmeceutical purposes.
Hyperloop Academic Research: A Systematic Review and a Taxonomy of Issues
Authors: Gkoumas Konstantinos
Published: June 2021

Hyperloop is a proposed very high-speed ground transportation system for both passenger and freight that has the potential to be revolutionary, and which has attracted much attention in the last few years. The concept was introduced in its modern form relatively recently, yet substantial progress has been made in the past years, with research and development taking place globally, from several Hyperloop companies and academics. This study examined the status of Hyperloop development and identified issues and challenges by means of a systematic review that analyzed 161 documents from the Scopus database on Hyperloop since 2014. Following that, a taxonomy of topics from scientific research was built under different physical and operational clusters. The findings could be of help to transportation academics and professionals who are interested in the developments in the field, and form the basis for policy decisions for the future implementation of Hyperloop.
Diamond-Shaped Extended Fins for Heat Transfer Enhancement in a Double-Pipe Heat Exchanger: An Innovative Design
Authors: Ishaq Muhammad , Ali Amjad , Amjad Muhammad , Syed Khalid Saifullah , Iqbal Zafar
Published: June 2021

Heat transfer enhancement in heat exchangers results in thermal efficiency and energy saving. In double-pipe heat exchangers (DPHEs), extended or augmented fins in the annulus of the two concentric pipes, i.e., at the outer surface of the inner pipe, are used to extend the surface of contact for enhancing heat transfer. In this article, an innovative diamond-shaped design of extended fins is proposed for DPHEs. This type of fin is considered for the first time in the design of DPHEs. The triangular-shaped and rectangular-shaped fin designs of DPHE, available in the literature, can be recovered as special cases of the proposed design. An h-adaptive finite element method is employed for the solution of the governing equations. The results are computed for various performance measures against the emerging parameters. The results dictate that the optimal configurations of the diamond-shaped fins in the DPHE for an enhanced heat transfer are recommended as follows: If around 4–6, 8–12, or 16–32 fins are to be placed in the DPHE, then the height of the fins should be 20%, 80%, or 100%, respectively, of the annulus width. If frictional loss of heat is also to be considered, then for fin-heights of 20–80% and 100% of the annulus width, the placement of 4 and 8 diamond-shaped fins, respectively, is recommended for an enhanced heat transfer. These recommendations are for the radii ratio (i.e., the ratio of the inner pipe radius to that of the outer pipe) of 0.25. The recommendations are be modified if the radii ratio is altered.
Combining Virtual Reality and Organizational Neuroscience for Leadership Assessment
Authors: Parra Elena , Chicchi Giglioli Irene Alice , Philip Jestine , Carrasco-Ribelles Lucia Amalia , Marín-Morales Javier , Alcañiz Raya Mariano
Published: June 2021

In this article, we introduce three-dimensional Serious Games (3DSGs) under an evidence-centered design (ECD) framework and use an organizational neuroscience-based eye-tracking measure to capture implicit behavioral signals associated with leadership skills. While ECD is a well-established framework used in the design and development of assessments, it has rarely been utilized in organizational research. The study proposes a novel 3DSG combined with organizational neuroscience methods as a promising tool to assess and recognize leadership-related behavioral patterns that manifest during complex and realistic social situations. We offer a research protocol for assessing task- and relationship-oriented leadership skills that uses ECD, eye-tracking measures, and machine learning. Seamlessly embedding biological measures into 3DSGs enables objective assessment methods that are based on machine learning techniques to achieve high ecological validity. We conclude by describing a future research agenda for the combined use of 3DSGs and organizational neuroscience methods for leadership and human resources.
Fischer-Tropsch Diesel and Biofuels Exergy and Energy Analysis for Low Emissions Vehicles
Authors: Torres Felipe Andrade , Doustdar Omid , Herreros Jose Martin , Li Runzhao , Poku Robert , Tsolakis Athanasios , Martins Jorge , Vieira de Melo Silvio A. B.
Published: June 2021

This research investigates the effects of a synthetic diesel-like fuel (Fischer-Tropsch diesel) and biofuels (ethanol and biodiesel) fuel blends on the energy-exergy efficiencies and gaseous exhaust emissions characteristics of a compression ignition engine. Two blends of alternative fuels denoted as E15B35FTD50 (15% ethanol, 35% biodiesel, and 50% Fischer-Tropsch diesel) and E15B35D50 (15% ethanol, 35% biodiesel, and 50% diesel) were experimentally studied on a single-cylinder diesel engine and compared to diesel fuel. The results show that the energetic and the exergetic efficiencies of the alternative fuels are comparable to those of the engine fueled with diesel fuel. The unburnt HC, NO, N2O, and NH3 emissions were reduced for the two alternative fuel blends compared to diesel, while CO emissions increased. The light HC species were found to slightly increase for the alternative fuel blends in comparison with diesel fuel. However, the total HC was considerably reduced by the combustion of E15B35FTD50 not only when compared to the diesel fuel combustion, but also when compared to E15B35D50. Overall, these results may contribute to identifying advantages and limitations in terms of energetic-exergetic analysis and emissions for the new generation of conventional diesel and hybrid electric vehicles that aim to achieve future emissions regulations.
Statistical Methods in Bidding Decision Support for Construction Companies
Authors: Leśniak Agnieszka
Published: June 2021

On the border of two phases of a building life cycle (LC), the programming phase (conception and design) and the execution phase, a contractor is selected. A particularly appropriate method of selecting a contractor for the construction market is the tendering system. It is usually based on quality and price criteria. The latter may involve the price (namely, direct costs connected with works realization as well as mark-ups, mainly overhead costs and profit) or cost (based on the life cycle costing (LCC) method of cost efficiency). A contractor’s decision to participate in a tender and to calculate a tender requires an investment of time and company resources. As this decision is often made in a limited time frame and based on the experience and subjective judgement of the contractor, a number of models have been proposed in the literature to support this process. The present paper proposes the use of statistical classification methods. The response obtained from the classification model is a recommendation to participate or not. A database consisting of historical data was used for the analyses. Two models were proposed: the LOG model—using logit regression and the LDA model—using linear discriminant analysis, which obtain better results. In the construction of the LDA model, the equation of the discriminant function was sought by indicating the statistically significant variables. For this purpose, the backward stepwise method was applied, where initially all input variables were introduced, namely, 15 identified bidding factors, and then in subsequent steps, the least statistically significant variables were removed. Finally, six variables (factors) were identified that significantly discriminate between groups: type of works, contractual conditions, project value, need for work, possible participation of subcontractors, and the degree of difficulty of the works. The model proposed in this paper using a discriminant analysis with six input variables achieved good performance. The results obtained prove that it can be used in practice. It should be emphasized, however, that mathematical models cannot replace the decision-maker’s thought process, but they can increase the effectiveness of the bidding decision.
Compressive and Diagonal Tension Strengths of Masonry Prisms Strengthened with Amorphous Steel Fiber-Reinforced Mortar Overlay
Authors: Yu Ji-Hoon , Park Ji-Hun
Published: June 2021

A technique for strengthening masonry walls by plastering with amorphous steel fiber-reinforced mortar (ASFRM) is investigated through compressive and diagonal tension tests for masonry prisms. The vertical joint between masonry units was not completely filled with mortar to mimic poor workmanship, which is typically reflected in low-cost buildings. The test variables include the number and thickness of mortar overlays, fiber volume fraction, and additional reinforcement using glass fiber mesh or shear connectors. In most strengthened specimens, the ASFRM is not damaged but separated from the masonry prisms after its maximum strength is reached. Additional tests for the bond strength between the ASFRM overlay and masonry surface are conducted to evaluate its contribution to the strengthening effects. Based on experimental observations, equations for predicting the compressive and diagonal tension strengths of masonry prisms strengthened with ASFRM are proposed. The compressive strength can be predicted more accurately by considering the asymmetrical distribution of compressive stress when strengthening is performed on only one side. The diagonal tension strength after strengthening can be predicted by incorporating the contribution of the bond strength between the ASFRM overlay and masonry prism to the initial strength.
Wind-Tunnel Studies on Sand Sedimentation Around Wind-Break Walls of Lanxin High-Speed Railway II and Its Prevention
Authors: Dun Hongchao , Xin Guowei , Huang Ning , Shi Guangtian , Zhang Jie
Published: June 2021

Wind-break walls along Lanxin High-Speed Railway II were studied and approved as effective measures to reduce strong wind damage to the high-speed trains. The results show that sand sedimentation on the leeward sides of wind-break walls along the railway within Gobi Desert could significantly threaten the operation safety of running trains. Different from the current sand sedimentation prevention measures without adequate consideration of the deposition process of airborne sand particles, this study revealed the mechanism of sand sedimentation on the leeward sides of three wind-break walls within different terrains. A series of wind-tunnel experiments were carried out to measure the horizontal velocity, number density, transport flux, and deposition rate of sand particles, and it was found that the horizontal speed of sand particles was first increased and then decreased on the railway track, and the peak speed over the concave subgrade was much smaller than those over convex and flat subgrades. The number density and horizontal sand flux were largest over the concave subgrade, and were the smallest over the convex subgrade. The sand particle deposition rate and distribution were also the largest within the concave subgrade, and some measures were also proposed to prevent sand sedimentation on the leeward sides of wind-break walls.
Comparison of CAD/CAM and Conventional Denture Base Resins: A Systematic Review
Authors: Batisse Cindy , Nicolas Emmanuel
Published: June 2021

At present, complete dentures (CDs) remain the only treatment available for the majority of edentulous patients. CDs are primarily fabricated using a conventional method using polymethylmethacrylate (PMMA) resin. The steps involved in PMMA polymerisation directly affect the quality of the resin prosthetic base and any error reduces retention and occlusal accuracy of CDs. Furthermore, when using the conventional technique, the residual monomer alters the resin mechanical properties and may cause mucosal reactions. Recently, computer aided design and computer aided manufacture (CAD/CAM) techniques were increasingly used to fabricate CDs by machining resin discs that have been manufactured under high pressure and temperature. This systematic review compares CAD/CAM and conventional CDs according to their mechanical, physical and chemical characteristics, as well as the clinical impact of any differences between them. A review was conducted according to the preferred reporting items for systematic reviews and meta-analyses checklist on 392 publications from both PubMed and backward research. Fifteen studies have been included. Results showed that CAD/CAM resins had globally better physical and mechanical properties than conventional resins. The use of machined resin could improve the clinical performance, maintenance and longevity of CDs. Further studies in clinical use would be required to complement these results.
Power-Flow and Mechanical Efficiency Computation in Two-Degrees-of-Freedom Planetary Gear Units: New Compact Formulas
Authors: Esmail Essam Lauibi , Pennestrì Ettore , Cirelli Marco
Published: June 2021

The mechanical efficiency is a computed value for comparing the performance of the multi degrees-of-freedom geared transmissions of hybrid vehicles. Most of the current methods for estimating gear trains mechanical efficiency require the decomposition of gear transmissions in basic structural elements or planetary gear units (PGU). These are two degrees-of-freedom components whose mechanical efficiency has a deep influence on the overall device. The authors (E.L.E., E.P.) already evidenced that, under certain kinematic conditions, the classic Radzimovsky’s formulas, widely accepted for computing the mechanical efficiency of PGUs, are not adequate. In this paper, more general and reliable formulas for computing the mechanical efficiency are deduced. The proposed formulas herein, exploiting the concept of potential or virtual power, evidence the dependency between kinematics and efficiency. A numerical example compares our results with previous work on the subject.
Independent Double-Boost Interleaved Converter with Three-Level Output
Authors: Suciu Vasile Mihai , Salcu Sorin Ionut , Pacuraru Alexandru Madalin , Pintilie Lucian Nicolae , Szekely Norbert Csaba , Teodosescu Petre Dorel
Published: June 2021

This paper introduces a novel converter topology based on an independent controlled double-boost configuration. The structure was achieved by combining two independent classic boost converters connected in parallel at the input and in series at the output. Through proper control of the two boost converters, an interleaved topology was obtained, which presents a low ripple for the input current. Being connected in series at the output, a three-level structure was attained with twice the voltage gain of classic boost and interleaved topologies. A significant feature of the proposed converter is the possibility of independent operation of the two integrated boost converters, in both symmetrical and asymmetrical modes. This feature may be particularly useful in voltage balancing or interconnection with bipolar DC grids/applications. The operation principle, simulations, mathematical analysis, and laboratory prototype experimental results are presented.
A Proposed In Vitro Methodology for Assessing the Accuracy of Three-Dimensionally Printed Dental Models and the Impact of Storage on Dimensional Stability
Authors: Lin Li Hsin , Granatelli Joshua , Alifui-Segbaya Frank , Drake Laura , Smith Derek , Ahmed Khaled E.
Published: June 2021

The objective of this study was to propose a standardised methodology for assessing the accuracy of three-dimensional printed (3DP) full-arch dental models and the impact of storage using two printing technologies. A reference model (RM) comprising seven spheres was 3D-printed using digital light processing (MAX UV, MAX) and stereolithography (Form 2, F2) five times per printer. The diameter of the spheres (n = 35) represented the dimensional trueness (DT), while twenty-one vectors (n = 105) extending between the sphere centres represented the full-arch trueness (FT). Samples were measured at two (T1) and six (T2) weeks using a commercial profilometer to assess their dimensional stability. Significant (p < 0.05) contraction in DT occurred at T1 and T2 with a medium deviation of 108 µm and 99 µm for MAX, and 117 µm and 118 µm for F2, respectively. No significant (p > 0.05) deviations were detected for FT. The detected median deviations were evenly distributed across the arch for MAX at <50 µm versus F2, where the greatest error of 278 µm was in the posterior region. Storage did not significantly impact the model’s DT in contrast to FT (p < 0.05). The proposed methodology was able to assess the accuracy of 3DP. Storage significantly impacted the full-arch accuracy of the models up to 6 weeks post-printing.
MenuNER: Domain-Adapted BERT Based NER Approach for a Domain with Limited Dataset and Its Application to Food Menu Domain
Authors: Syed Muzamil Hussain , Chung Sun-Tae
Published: June 2021

Entity-based information extraction is one of the main applications of Natural Language Processing (NLP). Recently, deep transfer-learning utilizing contextualized word embedding from pre-trained language models has shown remarkable results for many NLP tasks, including Named-entity recognition (NER). BERT (Bidirectional Encoder Representations from Transformers) is gaining prominent attention among various contextualized word embedding models as a state-of-the-art pre-trained language model. It is quite expensive to train a BERT model from scratch for a new application domain since it needs a huge dataset and enormous computing time. In this paper, we focus on menu entity extraction from online user reviews for the restaurant and propose a simple but effective approach for NER task on a new domain where a large dataset is rarely available or difficult to prepare, such as food menu domain, based on domain adaptation technique for word embedding and fine-tuning the popular NER task network model ‘Bi-LSTM+CRF’ with extended feature vectors. The proposed NER approach (named as ‘MenuNER’) consists of two step-processes: (1) Domain adaptation for target domain; further pre-training of the off-the-shelf BERT language model (BERT-base) in semi-supervised fashion on a domain-specific dataset, and (2) Supervised fine-tuning the popular Bi-LSTM+CRF network for downstream task with extended feature vectors obtained by concatenating word embedding from the domain-adapted pre-trained BERT model from the first step, character embedding and POS tag feature information. Experimental results on handcrafted food menu corpus from customers’ review dataset show that our proposed approach for domain-specific NER task, that is: food menu named-entity recognition, performs significantly better than the one based on the baseline off-the-shelf BERT-base model. The proposed approach achieves 92.5% F1 score on the YELP dataset for the MenuNER task.
Bioinspired Divide-and-Conquer Design Methodology for a Multifunctional Contour of a Curved Lever
Authors: Kim Jehyeok , Moon Junyoung , Ryu Jaewook , Lee Giuk
Published: June 2021

In this study, we propose a bioinspired design methodology for a multifunctional lever based on the morphological principle of the lever mechanism in the Salvia pratensis flower. The proposed divide-and-conquer contour design methodology does not treat a lever contour as a single curve that satisfies multiple functions. Rather, the lever contour combines partial contours to achieve its assigned subfunction. This approach can simplify the complex multifunctional problem in lever design. We include a case study of a lever utilized in a compact variable gravity compensator (CVGC) to explain the methodology in more detail. In the case study, four partial contours were designed to satisfy three types of functional requirements. The final design for the lever contour was manufactured and verified with visual measurement experiments. The experimental result shows that each partial contour successfully achieved its subfunctions.
Publisher’s Note: Architecture—A Journal of Practicality and Artistry
Authors: Liu Xiaoyan , Stefenelli Giulia , Lin Shu-Kun
Published: June 2021

MDPI has been celebrating its 25th Anniversary in 2021 [...]
Measurement and Modeling of the Precipitation Particle Size Distribution
Authors: Gatlin Patrick N. , Thurai Merhala , Williams Christopher , Adirosi Elisa
Published: June 2021

Precipitation plays a vital role within the Earth system [...]
Forest Fires in Madeira Island and the Fire Weather Created by Orographic Effects
Authors: Couto Flavio T. , Salgado Rui , Guiomar Nuno
Published: June 2021

Understanding the effects of weather and topography on fire spread in specific contexts, such as oceanic islands, is critical for supporting fire prevention and suppression strategies. In this study, we analyse the atmospheric conditions associated with historical forest fires that have occurred over complex terrain in Madeira Island, Portugal. The atmospheric Meso-NH model was used to identify the mesoscale environment during three forest fires events. The model was configured into two nested horizontal domains, the outer domain at 2.5 km resolution and the inner domain at 500 m. The paper brings a comprehensive analysis on the factors favouring the evolution of significant large fires occurring in Madeira Island in August 2010, July 2012 and August 2016. These fire events were selected because they are characterized by their large size (between 324.99 ha and 7691.67 ha) that expanded in a short-time period, threatening people and property in the wildland-urban interfaces. The study highlights that local terrain produce orographic effects that enhance the fire danger over the southern slope during typical summer atmospheric conditions.
Analysis of Sub-Daily Precipitation for the PannEx Region
Authors: Lakatos Monika , Szentes Olivér , Cindrić Kalin Ksenija , Nimac Irena , Kozjek Katja , Cheval Sorin , Dumitrescu Alexandru , Irașoc Adrian , Stepanek Petr , Farda Aleš , Kajaba Peter , Mikulová Katarína , Mihic Dragan , Petrovic Predrag , Chimani Barbara , Pritchard David
Published: June 2021

The PannEx is a GEWEX-initiated, community driven research network in the Pannonian Basin. One of the main scientific issues to address in PannEx is the investigation of precipitation extremes. Meteorological Services in the PannEx area collected the hourly precipitation data and commonly used a computer program, which was developed in the INTENSE project, to produce a set of global hydro-climatic indices. Calculations are carried out on data aggregated 1-, 3- and 6-h intervals. Selected indices are analyzed in this paper to assess the general climatology of the short-term precipitation in the Pannonian basin. The following indices are illustrated on maps and graphs: the annual mean and maxima of 1-h, 3-h and 6-h sums, the count of 3-hr periods greater than 20 mm thresholds, the maximum length of wet hours, the timing of wettest hour and the 1-h precipitation intensity. The seasonal trends of the 1-h precipitation intensity were tested from 1998 to 2019. Analysis of sub-daily precipitation has been limited by the availability of data on a global or a regional scale. The international effort made in this work through collaboration in the PannEx initiative contributes to enlarging the data availability for regional and global analysis of sub-daily precipitation extremes.
Studying a Long-Lasting Meteor Trail from Stereo Images and Radar Data
Authors: Vasilyev Roman V. , Syrenova Tatyana E. , Beletsky Alexander B. , Artamonov Maxim F. , Merzlyakov Eugeny G. , Podlesny Aleksey V. , Cedric Mark V.
Published: June 2021

Unique observation of a long-lasting meteor trail of about half an hour duration is described. The trail resulted from a burning meteor from the Leonid storm flux in the middle latitudes over eastern Siberia. We describe three-dimensional morphological characteristics of both the meteor and the long-lasting trail using data from wide-angle CCD cameras. Additionally, we present the meteor and the trail radiolocation characteristics obtained with a meteor radar and ionosonde. The background dynamics of the upper atmosphere at the height where the long-lasting trail developed were observed using data from the meteor radar and Fabry-Perot interferometer. The obtained results allowed the conclusion that the dynamics of a long-lasting trail are conditioned by the wind. However, during the first minutes of trail development, it is possible that a high-speed component is present, resulting from explosion of the meteor body in the atmosphere. A primitive spectral analysis of the long-lasting trail’s optical emissions and earlier studies point to hydroxyl molecules as a possible source of the glow. We believe the enhanced hydroxyl emission could be related to interaction of excited O(1D) oxygen atoms with meteor body water in the Earth’s upper atmosphere.
Which Is More Sensitive to Water Stress for Irrigation Scheduling during the Maturation Stage: Grapevine Photosynthesis or Berry Size?
Authors: Zhang Qingtao , Chen Yixuan , Xiong Yujiu , Moritani Shigeoki , Wu Xinyu , Yan Chunhua , Chen Xiaohong
Published: June 2021

To better understand the sensitivity of berry size and grapevine photosynthesis to water stress, and determine the soil water potential (ψ) threshold for scheduling irrigation during the maturation stage, we simultaneously measured berry size with photographs, leaf net photosynthesis with a portable meter, and ψ with tensiometers during the drying cycles for grapevines (Vitis vinifera L.). Our results showed that in berry development stage III (maturation), photosynthesis was more sensitive to water stress than berry size. When ψ decreased beyond −13.2 ± 0.82 kPa, photosynthesis, stomatal conductance, transpiration, and extrinsic (AN/E) and intrinsic (AN/gs) water use efficiency (WUE) decreased rapidly and did not recover thereafter. In contrast, the berry size remained close to unaffected by the decreasing ψ until it reached a value of −16.2 ± 0.77 kPa and, thereafter, the berry shrank significantly. In conclusion, we suggest that during the maturation stage of grapevines, for the potted mixture used in our experiments, irrigation should be triggered when the ψ reaches a value of −13.2 ± 0.82 kPa. Further, ψ should be kept lower than −6.9 ± 0.15 kPa after irrigation, because the highest values of intrinsic WUE (AN/gs) occurred when ψ decreased from −6.9 ± 0.15 to −14.6 ± 0.7 kPa. In arid areas, the threshold ψ should be considered as −16.2 ± 0.77 kPa during maturation to achieve high-efficiency use of water resources and sustainable production of grapevines.
Plant-Based Phytochemical Screening by Targeting Main Protease of SARS-CoV-2 to Design Effective Potent Inhibitors
Authors: Mahmud Shafi , Biswas Suvro , Paul Gobindo Kumar , Mita Mohasana Akter , Promi Maria Meha , Afrose Shamima , Hasan Md. Robiul , Zaman Shahriar , Uddin Md. Salah , Dhama Kuldeep , Emran Talha Bin , Saleh Md. Abu , Simal-Gandara Jesus
Published: June 2021

Currently, a worldwide pandemic has been declared in response to the spread of coronavirus disease 2019 (COVID-19), a fatal and fast-spreading viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The low availability of efficient vaccines and treatment options has resulted in a high mortality rate, bringing the world economy to its knees. Thus, mechanistic investigations of drugs capable of counteracting this disease are in high demand. The main protease (Mpro) expressed by SARS-CoV-2 has been targeted for the development of potential drug candidates due to the crucial role played by Mpro in viral replication and transcription. We generated a phytochemical library containing 1672 phytochemicals derived from 56 plants, which have been reported as having antiviral, antibacterial, and antifungal activity. A molecular docking program was used to screen the top three candidate compounds: epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate, which had respective binding affinities of −8.4, −8.5, and −8.8 kcal/mol. Several active sites in the targeted protein, including Cys145, His41, Met49, Glu66, and Met165, were found to interact with the top three candidate compounds. The multiple simulation profile, root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and solvent-accessible surface area values supported the inflexible nature of the docked protein–compound complexes. The toxicity and carcinogenicity profiles were assessed, which showed that epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate had favorable pharmacological properties with no adverse effects. These findings suggest that these compounds could be developed as part of an effective drug development pathway to treat COVID-19.
Functional Implications of the Dynamic Regulation of EpCAM during Epithelial-to-Mesenchymal Transition
Authors: Brown Taylor C. , Sankpal Narendra V. , Gillanders William E.
Published: June 2021

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis. EpCAM is a target of molecular therapies and plays a prominent role in tumor biology. In this review, we focus on the dynamic regulation of EpCAM expression during epithelial-to-mesenchymal transition (EMT) and the functional implications of EpCAM expression on the regulation of EMT. EpCAM is frequently and highly expressed in epithelial cancers, while silenced in mesenchymal cancers. During EMT, EpCAM expression is downregulated by extracellular signal-regulated kinases (ERK) and EMT transcription factors, as well as by regulated intramembrane proteolysis (RIP). The functional impact of EpCAM expression on tumor biology is frequently dependent on the cancer type and predominant oncogenic signaling pathways, suggesting that the role of EpCAM in tumor biology and EMT is multifunctional. Membrane EpCAM is cleaved in cancers and its intracellular domain (EpICD) is transported into the nucleus and binds β-catenin, FHL2, and LEF1. This stimulates gene transcription that promotes growth, cancer stem cell properties, and EMT. EpCAM is also regulated by epidermal growth factor receptor (EGFR) signaling and the EpCAM ectoderm (EpEX) is an EGFR ligand that affects EMT. EpCAM is expressed on circulating tumor and cancer stem cells undergoing EMT and modulates metastases and cancer treatment responses. Future research exploring EpCAM’s role in EMT may reveal additional therapeutic opportunities.
3D Collagen Hydrogel Promotes In Vitro Langerhans Islets Vascularization through ad-MVFs Angiogenic Activity
Authors: Salamone Monica , Rigogliuso Salvatrice , Nicosia Aldo , Campora Simona , Bruno Carmelo Marco , Ghersi Giulio
Published: June 2021

Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33–955 μm that are able to maintain their original morphology. The isolated units of ad-MVFs that resulted were able to activate transcriptional switching toward angiogenesis, forming tubes, branches, and entire capillary networks when cultured in 3D collagen type-I hydrogel. The proper involvement of metalloproteases (MMP2/MMP9) and serine proteases in basal lamina and extracellular matrix ECM degradation during the angiogenesis were concurrently assessed by the evaluation of alpha-smooth muscle actin (αSMA) expression. These results suggest that collagen type-I hydrogel provides an adequate 3D environment supporting the activation of the vascularization process. As a proof of concept, we exploited 3D collagen hydrogel for the setting of ad-MVF–islet of Langerhans coculture to improve the islets vascularization. Our results suggest potential employment of the proposed in vitro system for regenerative medicine applications, such as the improving of the islet of Langerhans engraftment before transplantation.
BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment
Authors: Gojkovic Slaven , Krezic Ivan , Vranes Hrvoje , Zizek Helena , Drmic Domagoj , Horvat Pavlov Katarina , Petrovic Andrea , Batelja Vuletic Lovorka , Milavic Marija , Sikiric Suncana , Stilinovic Irma , Samara Mariam , Knezevic Mario , Barisic Ivan , Sjekavica Ivica , Lovric Eva , Skrtic Anita , Seiwerth Sven , Sikiric Predrag
Published: June 2021

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat.
Fracture Healing Research—Shift towards In Vitro Modeling?
Authors: Pfeiffenberger Moritz , Damerau Alexandra , Lang Annemarie , Buttgereit Frank , Hoff Paula , Gaber Timo
Published: June 2021

Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.
Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model
Authors: Oliveira Fernando A. , Nucci Mariana P. , Mamani Javier B. , Alves Arielly H. , Rego Gabriel N. A. , Kondo Andrea T. , Hamerschlak Nelson , Junqueira Mara S. , de Souza Lucas E. B. , Gamarra Lionel F.
Published: June 2021

This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical–chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 104 SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11–120 days), achieving a peak of intensity at 30 days, which remained stable around 108 photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation.
Chemical and Biological Molecules Involved in Differentiation, Maturation, and Survival of Dopaminergic Neurons in Health and Parkinson’s Disease: Physiological Aspects and Clinical Implications
Authors: Gaggi Giulia , Di Credico Andrea , Izzicupo Pascal , Iannetti Giovanni , Di Baldassarre Angela , Ghinassi Barbara
Published: June 2021

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD.
Studying the Degree of Tooth Enamel Mineralization through Raman Spectroscopy in Various Spectral Ranges
Authors: Prikule Diana V. , Kukushkin Vladimir I. , Mitronin Aleksandr V. , Prikuls Vladislav F.
Published: June 2021

In vitro and in vivo methods of Raman spectroscopy have been developed to assess the degree of mineralization of the enamel of different functional groups. This article presents comparative studies that were carried out using scanning Raman microspectroscopy with various sources of laser excitation with wavelengths of 532, 785, and 1064 nm. It is shown that the intensity of Raman scattering of enamel can be a measure of its thickness. The obtained dependence of the Raman scattering intensity on the distance from the incisal edge is in good agreement with the literature data, where two independent methods (computer tomography and electron microscopy) are used to determine the enamel thickness values. The proposed methods can be considered as potential quantitative methods for express diagnostics of the state of tooth enamel in vivo.
The Effect of Comorbid Attention-Deficit/Hyperactivity Disorder Symptoms on Face Memory in Children with Autism Spectrum Disorder: Insights from Transdiagnostic Profiles
Authors: Chen Qi , Wang Zengjian , Wan Bin , Chen Qingxin , Zhai Kun , Jin Yu
Published: June 2021

Face memory impairments are common but heterogeneous in autism spectrum disorder (ASD), which may be influenced by co-occurrence with attention-deficit/hyperactivity disorder (ADHD). Here, we aimed to investigate the phenotype change of face memory in children with ASD comorbid ADHD symptoms, and discuss the potential role of executive function (EF). Ninety-eight children were analyzed in the present study, including ASD− (ASD-only, n = 24), ADHD (n = 23), ASD+ (with ADHD symptoms, n = 23) and neurotypical controls (NTC, n = 28). All participants completed two tests: face encoding and retrieving task and Wisconsin Card Sorting Test (WCST) for measuring face memory and EF, respectively. Results revealed that: compared with the NTC group, children with ASD− exhibited lower accuracy in both face encoding and retrieving, and participants with ASD+ showed lower accuracy only in the retrieving, whereas no differences were found among participants with ADHD. Moreover, in the ASD+ group, face encoding performance was correlated with response perseverative errors (RPE) and failure to maintain sets (FMS) of WCST; significantly, there were no group differences between ASD+ and NTC in these two indices. The transdiagnostic profiles indicated that comorbid ADHD symptoms could modulate the face encoding deficiency of ASD, which may be partially compensated by EF. Shared and distinct intervention strategies to improve social cognition are recommended for children undergoing treatment for each condition.
Should Echolalia Be Considered a Phonic Stereotypy? A Narrative Review
Authors: Pruccoli Jacopo , Spadoni Chiara , Orsenigo Alex , Parmeggiani Antonia
Published: June 2021

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) defines echolalia as a pathological, parrotlike, and apparently senseless repetition (echoing) of a word or phrase just uttered by another person and classifies this condition among the “restrictive and repetitive behaviours” of Autism Spectrum Disorder (ASD). The authors reviewed the existing literature on echolalia and its role in the development of children with ASD. Current conceptualizations include echolalia among repetitive behaviors and stereotypies and thus interpret this symptom as lacking any communicative significance, with negative effects on learning and sensory processing. Echoic behaviors, however, have been described in neurotypical infants and children as having a substantial effect on the consequent development of language and communication. Relevant research has documented a functional role of echolalia in ASD children as well since it facilitates the acquisition of verbal competencies and affords a higher degree of semantic generalization. This developmental function could be restricted to specific contexts. Considering echolalia as stereotypy and treating it as a disturbing symptom could impair the development of ASD-specific learning and communication processes. In light of this evidence, the authors propose a different conceptualization of echolalia and suggest that this symptom be considered among atypical communication patterns in children with ASD, with implications for treatment and prognosis.