bluuebunny/crossref_metadata_2025 huggingface dataset:
MA-XRF for the Characterisation of the Painting Materials and Technique of the Entombment of Christ by Rogier van der Weyden
Authors: Mazzinghi Anna , Ruberto Chiara , Castelli Lisa , Czelusniak Caroline , Giuntini Lorenzo , Mandò Pier Andrea , Taccetti Francesco
Published: July 2021

At present, macro X-ray fluorescence (MA-XRF) is one of the most essential analytical methods exploited by heritage science. By providing spatial distribution elemental maps, not only does it allow for material characterisation but also to understand, or at least to have a likely idea of, the production techniques of an analysed object. INFN-CHNet, the Cultural Heritage Network of the Italian National Institute of Nuclear Physics, designed and developed a MA-XRF scanner aiming to be a lightweight, easy to transport piece of equipment for use in in situ measurements. In this study, the INFN-CHNet MA-XRF scanner was employed for the analysis of a painting by the Flemish artist Rogier van der Weyden. The painting belongs to the collection of the Uffizi gallery in Florence and was analysed during conservation treatments at the Opificio delle Pietre Dure, one of the main conservation centres in Italy. The research aims were to characterise the materials employed by the artist and to possibly understand his painting technique. Although MA-XRF alone cannot provide a comprehensive characterisation, it nonetheless proved to be an invaluable tool for providing an initial overview or hypothesis of the painting materials and techniques used.
Design of JET Humanoid Robot with Compliant Modular Actuators for Industrial and Service Applications
Authors: Sim Jaehoon , Kim Seungyeon , Park Suhan , Kim Sanghyun , Kim Mingon , Park Jaeheung
Published: July 2021

This paper presents the development of the JET humanoid robot, which is based on the existing THORMANG platform developed in 2015. Application in the industrial and service fields was targeted, and three design concepts were determined for the humanoid robot. First, low stiffness of the actuator modules was utilized for compliance with external environments. Second, to maximize the robot whole-body motion capability, the overall height was increased. However, the weight was reduced to satisfy power requirements. The workspace was also increased to enable various postures, by increasing the range of motion of each joint and extending the links. Compared to the original THORMANG platform, the lower limb length increased by approximately 20%, and the hip range of motion increased by 39.3%. Third, the maintenance process was simplified through modularization of the electronics and frame design for improved accessibility. Several experiments, including stair climbing and egress from a car, were performed to verify that the JET humanoid robot performance enhancements reflected the design concepts.
Rapid Analysis of Chemical Composition and Physical Properties of Gemstones Using LIBS and Chemometric Technique
Authors: Dubey Sonali , Kumar Rohit , Rai Abhishek K. , Pati Jayanta K. , Kiefer Johannes , Rai Awadhesh K.
Published: July 2021

Laser-induced breakdown spectroscopy (LIBS), accompanied by chemometric data analysis, is used to identify and classify gemstones of various hardness. The study involves several gemstones: amethyst, aquamarine beryl, bloodstone citrine, diopside, and enstatite. Their hardness is determined through a correlation utilizing the spectral intensity ratio of the ionic to atomic spectral lines of an identified element in the LIB spectrum. The result of the relative hardness obtained from the LIBS analysis is in good agreement with the hardness measured from Mohs’s scale of hardness, a popular qualitative method to determine hardness. In this work, a linear relationship has been established between the Mohs’s hardness and the plasma excitation temperature. Thus, the hardness of the gemstones can be determined with the help of plasma excitation temperature. Moreover, the analysis of trace elements in LIB spectral data reveals that a particular element is responsible for the colors of gemstones. Therefore, the relative concentration of constituents is calculated for all gemstones and compared. Principal component analysis (PCA) is successfully applied to all gemstone spectra for rapid classification and discrimination based on their variable elemental concentrations and respective hardness.
Mushroom Ligninolytic Enzymes―Features and Application of Potential Enzymes for Conversion of Lignin into Bio-Based Chemicals and Materials
Authors: Kim Seonghun
Published: July 2021

Mushroom ligninolytic enzymes are attractive biocatalysts that can degrade lignin through oxido-reduction. Laccase, lignin peroxidase, manganese peroxidase, and versatile peroxidase are the main enzymes that depolymerize highly complex lignin structures containing aromatic or aliphatic moieties and oxidize the subunits of monolignol associated with oxidizing agents. Among these enzymes, mushroom laccases are secreted glycoproteins, belonging to a polyphenol oxidase family, which have a powerful oxidizing capability that catalyzes the modification of lignin using synthetic or natural mediators by radical mechanisms via lignin bond cleavage. The high redox potential laccase within mediators can catalyze the oxidation of a wide range of substrates and the polymerization of lignin derivatives for value-added chemicals and materials. The chemoenzymatic process using mushroom laccases has been applied effectively for lignin utilization and the degradation of recalcitrant chemicals as an eco-friendly technology. Laccase-mediated grafting has also been employed to modify lignin and other polymers to obtain novel functional groups able to conjugate small and macro-biomolecules. In this review, the biochemical features of mushroom ligninolytic enzymes and their potential applications in catalytic reactions involving lignin and its derivatives to obtain value-added chemicals and novel materials in lignin valorization are discussed.
Binary Ghost Imaging Based on the Fuzzy Integral Method
Authors: Yang Xu , Hu Jiemin , Wu Long , Xu Lu , Lyu Wentao , Yang Chenghua , Zhang Wei
Published: July 2021

The reconstruction quality of binary ghost imaging depends on the speckle binarization process. In order to obtain better binarization speckle and improve the reconstruction quality of binary ghost imaging, a local adaptive binarization method based on the fuzzy integral is proposed in this study. There are three steps in the proposed binarization process. The first step is to calculate the integral image of the speckle with the summed-area table algorithm. Secondly, the fuzzy integral image is calculated through the discrete Choquet integral. Finally, the binarization threshold of each pixel of the speckle is selected based on the calculated fuzzy integral result. The experiment results verify the feasibility of the proposed method. Compared with other methods qualitatively and quantitatively, the proposed method has high performance in reconstructing image of target.
Black on White: Microbial Growth Darkens the External Marble of Florence Cathedral
Authors: Santo Alba Patrizia , Cuzman Oana Adriana , Petrocchi Dominique , Pinna Daniela , Salvatici Teresa , Perito Brunella
Published: July 2021

Weathering processes seriously affect the durability of outdoor marble monuments. In urban environments, a very common deterioration phenomenon is the dark discoloration or blackening of marble. This paper describes a multidisciplinary study on the state of conservation of white marbles of the Florence Cathedral and the microbial community involved in their deterioration. The study is focused on the widespread dark discoloration of marble analyzed in two differently exposed sites of the Cathedral. It aims to provide information useful for future interventions to control the microbial growth. By chemical and petrographic analysis, in situ and ex situ microscopy, and cultivation and identification of microorganisms, it was found that (i) the darkening is mainly due to the growth of black fungi and dark cyanobacteria and (ii) the state of conservation of marble and the growth pattern of microorganisms seems to be linked to the microclimatic conditions, in particular to solar radiation exposure. This is the first report on the lithobiontic community inhabiting the Florence Cathedral marbles, with a more detailed investigation of the culturable mycobiota.
Considerations about Parameters Estimation into a Minimum Variance Control System
Authors: Filip Ioan , Dragan Florin , Szeidert Iosif
Published: July 2021

The starting point to design a minimum variance control law consists in identifying a linearized mathematical model (valid around an operating point) of a nonlinear process, respectively the on-line estimation of the parameters of this model. This paper presents a comparative study regarding the estimation of these parameters for the case when the process operates in open-loop, respectively the process is integrated into a closed-loop system specific to a minimum variance control. The comparison is made both analytically (for the general case) and through a validation study (by simulation) particularized for the case of an induction generator integrated into a wind energy conversion system. The main contribution of this paper consists in proving the fact that, in closed-loop (under the constraints imposed by the control law), the process parameters estimates differ from the real ones identified in open-loop (in free operating mode, without constraints). In addition, as a novelty, the paper demonstrates that, in steady-state, the process gain estimates are identical, both in closed-loop and open-loop, even though they are calculated based on different estimates of these linear model parameters. Thus, based on parameters estimates in closed-loop, the parameter estimator rather allows the estimation of the real process gain, although it does not accurately estimate the real values of the linearized model parameters (correctly estimated only in open-loop).
Design and Implementation of an Autonomous Charging Station for Agricultural Electrical Vehicles
Authors: Harik El Houssein Chouaib
Published: July 2021

One of the goals in adopting more sustainable agricultural practices is to reduce green-house-gas emissions from current practices by replacing fossil-fuel-based heavy machinery with lighter, electrical ones. In a not-so-distant scenario where a single farmer owns a fleet of small electrical tractors/robots that can operate in an autonomous/semi-autonomous manner, this will bring along some logistic challenges. It will be highly impractical that the farmer follows each time a given vehicle moves to the charging point to manually charge it. We present in this paper the design and implementation of an autonomous charging station to be used for that purpose. The charging station is a combination of a holonomic mobile platform and a collaborative robotic arm. Vision-based navigation and detection are used in order to plug the power cable from the wall-plug to the vehicle and back to the wall-plug again when the vehicle has recharged its batteries or reached the required level to pursue its tasks in the field. A decision-tree-based scheme is used in order to define the necessary pick, navigate, and plug sequences to fulfill the charging task. Communication between the autonomous charging station and the vehicle is established in order to make the whole process completely autonomous without any manual intervention. We present in this paper the charging station, the docking mechanism, communication scheme, and the deployed algorithms to achieve the autonomous charging process for agricultural electrical vehicles. We also present real experiments performed using the developed platform on an electrical robot-tractor.
A Novel Whale Optimization Algorithm for the Design of Tuned Mass Dampers under Earthquake Excitations
Authors: Lara-Valencia Luis A. , Caicedo Daniel , Valencia-Gonzalez Yamile
Published: July 2021

This paper introduces a novel methodology for the optimum design of linear tuned mass dampers (TMDs) to improve the seismic safety of structures through a novel Whale Optimization Algorithm (WOA). The algorithm is aimed to reduce the maximum horizontal peak displacement of the structure, and the root mean square (RMS) response of displacements as well. Furthermore, four additional objective functions, derived from multiple weighted linear combinations of the two previously mentioned parameters, are also studied in order to obtain the most efficient TMD design configuration. The differential evolution method (DEM), whose effectiveness has been previously demonstrated for TMD applications, and an exhaustive search (ES) process, with precision to two decimal positions, are used to compare and validate the results computed through WOA. Then, the proposed methodology is applied to a 32-story case-study derived from an actual building, and multiple ground acceleration time histories are considered to assess its seismic performance in the linear-elastic range. The numerical results show that the proposed methodology based on WOA is effective in finding the optimal TMD design configuration under earthquake loads. Finally, practical design recommendations are provided for TMDs, and the robustness of the optimization is demonstrated.
Prediction and Source Contribution Analysis of PM2.5 Using a Combined FLEXPART Model and Bayesian Method over the Beijing-Tianjin-Hebei Region in China
Authors: Guo Lifeng , Chen Baozhang , Zhang Huifang , Fang Jingchun
Published: July 2021

Fine particulate matter (PM2.5) has a serious impact on human health. Forecasting PM2.5 levels and analyzing the pollution sources of PM2.5 are of great significance. In this study, the Lagrangian particle dispersion (LPD) model was developed by combining the FLEXPART model and the Bayesian inventory optimization method. The LPD model has the capacity for real-time forecasting and determination of pollution sources of PM2.5, which refers to the contribution ratio and spatial distribution of each type of pollution (industry, power, residential, and transportation). In this study, we applied the LPD model to the Beijing-Tianjin-Hebei (BTH) region to optimize the a priori PM2.5 emission inventory estimates during 15–20 March 2018. The results show that (1) the a priori estimates have a certain degree of overestimation compared with the a posteriori flux of PM2.5 for most areas of BTH; (2) after optimization, the correlation coefficient (R) between the forecasted and observed PM2.5 concentration increased by an average of approximately 10%, the root mean square error (RMSE) decreased by 30%, and the IOA (index of agreement) index increased by 16% at four observation sites (Aotizhongxin_Beijing, Beichenkejiyuanqu_Tianjin, Dahuoquan_Xintai, and Renmingongyuan_Zhangjiakou); and (3) the main sources of pollution at the four sites mainly originated from industrial and residential emissions, while power factory and transportation pollution accounted for only a small proportion. The concentration of PM2.5 forecasts and pollution sources in each type of analysis can be used as corresponding reference information for environmental governance and protection of public health.
Analysis of a New Index for the Thermal Performance of Horizontal Opaque Building Components in Summer
Authors: Akbari Hashem , Lodi Chiara , Muscio Alberto , Tartarini Paolo
Published: July 2021

The summer behavior of an opaque building component subjected to the solar cycle depends on the combination of its thermal insulation, inertia, and solar reflectance. To rate the component dynamic behavior while an air conditioning system ensures a steady indoor temperature, a ‘solar transmittance index’ (STI) has been proposed. This is a component-based index calculated from a ‘solar transmittance factor’ (STF). STI takes into account the radiative properties at the outer surface and the thermophysical properties and layer structure of the materials beneath. It correlates the peak heat flux and temperature at the inner surface, relevant to cooling energy and thermal comfort, to the peak solar irradiance. Similar to the well-known ‘solar reflectance index’, STI is determined comparing the STF with two reference values, corresponding to a performance relatively low and very high, respectively. Thanks to its simplicity, the approach may allow defining easy to apply requirements to prevent building overheating, improve indoor comfort, reduce cooling energy demand, and mitigate some fallouts of the urban heat island effect. In this work, focused on roofs above occupied attics, peak heat flux and ceiling temperature are calculated by numerical simulation and compared with STF values for a wide range of roof types.
The Phenolic Compounds in the Young Shoots of Selected Willow Cultivars as a Determinant of the Plants’ Attractiveness to Cervids (Cervidae, Mammalia)
Authors: Budny Maciej , Zalewski Kazimierz , Stolarski Mariusz Jerzy , Wiczkowski Wiesław , Okorski Adam , Stryiński Robert
Published: July 2021

This study examined the phenolic acids, flavonoids, and salicylates contents in young, 3-month-old shoots (including the leaves) of willow (Salix spp.). The cultivars were selected based on experiments carried out previously in Poland on fodder and energy willows. It was found, using the HPLC-MS/MS method, that the willow cultivars analyzed from three experimental plots, contained nine different phenolic acids, five salicylates and nine flavonoids, including four flavanols (quercetin, kaempferol, taxifolin and isorhamnetin), two flavanones (prunin, naringenin), two flavones (luteolin, apigenin) and one flavan-3-ol (catechin). The contents of individual compounds were not identical and depended on the cultivar from which they were isolated. The S. laurina 220/205 and S. amygdalina Krakowianka contained the greatest amounts of phenolic acids. The lowest quantities of these compounds were found in the S. viminalis Tur, S. pantaderana and S. cordata clone 1036. The highest concentration of flavonoids in young stems was found in S. fragilis clone 1043. The S. purpurea clone 1131 contained the highest amounts of salicylic compounds. Based on the results obtained from all experimental plots, it was shown that there is a negative correlation between the extent of browsing damage and the content of helicine and salicin from the group of salicylic compounds. A similar analysis between the phenolic acid concentration and the degree of willow browsing showed a positive correlation, especially between ferulic, trans-cinnamic, and synapinic acid. A negative correlation was found between the concentration of protocatechic acid content and browsing by cervids.
Contiguity and Structural Impacts of a Non-Myosin Protein within the Thick Filament Myosin Layers
Authors: Menard Lynda M. , Wood Neil B. , Vigoreaux Jim O.
Published: July 2021

Myosin dimers arranged in layers and interspersed with non-myosin densities have been described by cryo-EM 3D reconstruction of the thick filament in Lethocerus at 5.5 Å resolution. One of the non-myosin densities, denoted the ‘red density’, is hypothesized to be flightin, an LMM-binding protein essential to the structure and function of Drosophila indirect flight muscle (IFM). Here, we build upon the 3D reconstruction results specific to the red density and its engagement with the myosin coiled-coil rods that form the backbone of the thick filament. Each independent red density winds its way through the myosin dimers, such that it links four dimers in a layer and one dimer in a neighboring layer. This area in which three distinct interfaces within the myosin rod are contacted at once and the red density extends to the thick filament core is designated the “multiface”. Present within the multiface is a contact area inclusive of E1563 and R1568. Mutations in the corresponding Drosophila residues (E1554K and R1559H) are known to interfere with flightin accumulation and phosphorylation in Drosophila. We further examine the LMM area in direct apposition to the red density and identified potential binding residues spanning up to ten helical turns. We find that the red density is associated within an expanse of the myosin coiled-coil that is unwound by the third skip residue and the coiled-coil is re-oriented while in contact with the red density. These findings suggest a mechanism by which flightin induces ordered assembly of myosin dimers through its contacts with multiple myosin dimers and brings about reinforcement on the level of a single myosin dimer by stabilization of the myosin coiled-coil.
Role of Endocrine System in the Regulation of Female Insect Reproduction
Authors: Khalid Muhammad Zaryab , Ahmad Sajjad , Ngegba Patrick Maada , Zhong Guohua
Published: July 2021

The proper synthesis and functioning of ecdysteroids and juvenile hormones (JHs) are very important for the regulation of vitellogenesis and oogenesis. However, their role and function contrast among different orders, and even in the same insect order. For example, the JH is the main hormone that regulates vitellogenesis in hemimetabolous insect orders, which include Orthoptera, Blattodea, and Hemiptera, while ecdysteroids regulate the vitellogenesis among the insect orders of Diptera, some Hymenoptera and Lepidoptera. These endocrine hormones also regulate each other. Even at some specific stage of insect life, they positively regulate each other, while at other stages of insect life, they negatively control each other. Such positive and negative interaction of 20-hydroxyecdysone (20E) and JH is also discussed in this review article to better understand the role of these hormones in regulating the reproduction. Therefore, the purpose of the present review is to deeply understand the complex interaction of endocrine hormones with each other and with the insulin signaling pathway. The role of microbiomes in the regulation of the insect endocrine system is also reviewed, as the endocrine hormones are significantly affected by the compounds produced by the microbiota.
Testosterone Levels in Adolescents and Young Men with Type 1 Diabetes and Their Association with Diabetic Nephropathy
Authors: Kang Jeongwoo , Choi Han Saem , Choi Young Ha , Oh Jun Suk , Song Kyungchul , Suh Junghwan , Kwon Ahreum , Kim Ho-Seong , Chae Hyun Wook
Published: July 2021

The association between serum testosterone levels and type 1 diabetes (T1D), especially in adolescents and young adults, has not been fully investigated. We aimed to compare testosterone levels between adolescents/young men with T1D and controls and to determine the factors affecting testosterone levels. We enrolled 47 men with T1D and 32 controls aged 15–29 years. We evaluated anthropometric measurements, lipid profiles, diabetic complications, and levels of serum luteinizing hormone, follicle-stimulating hormone, hemoglobin A1c, 24-h urine albumin, insulin autoantibody, and total serum testosterone. We assessed the correlation between serum testosterone levels and clinical characteristics. Total testosterone levels were higher in T1D patients than in controls (694.6 ± 182.2 vs. 554.1 ± 147.3 ng/dL, p = 0.001), and 24-h urine albumin level positively correlated with total testosterone levels (correlation coefficient 0.415, p = 0.004). T1D patients with nephropathy showed higher total testosterone levels than those without nephropathy (778.4 ± 198.9 vs. 655.4 ± 162.5 ng/dL, p = 0.029). However, diabetic nephropathy and testosterone levels were not significantly associated after adjusting for confounders (β ± SE 77.5 ± 55.2, p = 0.169). Further longitudinal studies are imperative to confirm a causal relationship between testosterone levels and T1D.
Postoperative Stroke after Spinal Anesthesia and Responses of Carotid or Cerebral Blood Flow and Baroreflex Functionality to Spinal Bupivacaine in Rats
Authors: Poon Yan-Yuen , Liu Yueh-Wei , Huang Ya-Hui , Chan Samuel H. H. , Tsai Ching-Yi
Published: July 2021

Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia prompted us to assess whether spinal bupivacaine may compromise carotid or cerebral blood flow. Postoperative examination after the stroke incident revealed that all three patients shared a common pathology of stenosis or atheromatosis in the carotid or middle cerebral artery. In a companion study using 69 Sprague-Dawley rats, subarachnoid application of bupivacaine elicited an initial (Phase I) reduction in the mean arterial pressure, carotid blood flow (CBF) and baroreflex-mediated sympathetic vasomotor tone, all of which subsequently returned to baseline (Phase II). Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in the cerebral cortex remained unaltered. However, in one-third of the rats studied, Phase II gave way to Phase III characterized by secondary hypotension and depressed baroreflex-mediated sympathetic vasomotor tone, along with declined HR, sustained cardiac vagal baroreflex, decreased BEI, reduced CBF and waning tissue perfusion or oxygen in the cerebral cortex. We concluded that carotid and cerebral blood flow can indeed be compromised after spinal anesthesia, and an impaired baroreflex-mediated sympathetic vasomotor tone, which leads to hypotension, plays a contributory role.
Regulation of S100A10 Gene Expression
Authors: Głowacka Aleksandra , Bieganowski Paweł , Jurewicz Ewelina , Leśniak Wiesława , Wilanowski Tomasz , Filipek Anna
Published: July 2021

S100A10, a member of the S100 family of Ca2+-binding proteins, is a widely distributed protein involved in many cellular and extracellular processes. The best recognized role of S100A10 is the regulation, via interaction with annexin A2, of plasminogen conversion to plasmin. Plasmin, together with other proteases, induces degradation of the extracellular matrix (ECM), which is an important step in tumor progression. Additionally, S100A10 interacts with 5-hydroxytryptamine 1B (5-HT1B) receptor, which influences neurotransmitter binding and, through that, depressive symptoms. Taking this into account, it is evident that S100A10 expression in the cell should be under strict control. In this work, we summarize available literature data concerning the physiological stimuli and transcription factors that influence S100A10 expression. We also present our original results showing for the first time regulation of S100A10 expression by grainyhead-like 2 transcription factor (GRHL2). By applying in silico analysis, we have found two highly conserved GRHL2 binding sites in the 1st intron of the gene encoding S100A10 protein. Using chromatin immunoprecipitation (ChIP) and luciferase assays, we have shown that GRHL2 directly binds to these sites and that this DNA region can affect transcription of S100A10.
Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties
Authors: Velderrain-Rodríguez Gustavo R. , Quero Javier , Osada Jesús , Martín-Belloso Olga , Rodríguez-Yoldi María Jesús
Published: July 2021

In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 ± 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 ± 10.70 and 181.68 ± 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 ± 0.06 kcal/100 g and 219.62 ± 0.49 kcal/100 g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 ± 40 µg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 ± 21 µg/mL) and seed coat (340 ± 32 µg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hydroxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer.
Puerarin Attenuates Cadmium-Induced Neuronal Injury via Stimulating Cadmium Excretion, Inhibiting Oxidative Stress and Apoptosis
Authors: Wen Shuangquan , Wang Li , Zou Hui , Gu Jianhong , Song Ruilong , Bian Jianchun , Yuan Yan , Liu Zongping
Published: July 2021

Cadmium (Cd) is a potential pathogenic factor in the nervous system associated with various neurodegenerative disorders. Puerarin (Pur) is an isoflavone purified from the Chinese medical herb, kudzu root, and exhibits antioxidant and antiapoptotic properties in the brain. In this study, the detailed mechanisms underlying the neuroprotective potential of Pur against Cd-induced neuronal injury was evaluated for the first time in vivo in a rat model and in vitro using primary rat cerebral cortical neurons. The results of the in vivo experiments showed that Pur ameliorated Cd-induced neuronal injury, reduced Cd levels in the cerebral cortices, and stimulated Cd excretion in Cd-treated rats. We also observed that the administration of Pur rescued Cd-induced oxidative stress, and attenuated Cd-induced apoptosis by concomitantly suppressing both the Fas/FasL and mitochondrial pathways in the cerebral cortical neurons of rats both in vivo and in vitro. Our results demonstrate that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons.
Poly (ADP-Ribose) Polymerase Inhibitor, ABT888, Improved Cisplatin Effect in Human Oral Cell Carcinoma
Authors: Paterniti Irene , Scuderi Sarah Adriana , Casili Giovanna , Lanza Marika , Mare Marzia , Giuffrida Raffella , Colarossi Cristina , Portelli Marco , Cuzzocrea Salvatore , Esposito Emanuela
Published: July 2021

Cisplatin is one of the chemotherapeutic drugs used for the management of oral carcinoma, in which combined therapies are estimated to exert superior therapeutic efficacy compared with monotherapy. It is known that poly(ADP-ribosyl)ation is implicated in a multiplicity of cellular activities, such as DNA repair and cell death. Based on these, PARP inhibitors are used for the treatment of cancers; however, the capacity of PARP inhibitors associated to anti-cancer drugs have not been completely assessed in oral carcinoma. Here, we evaluated the effects of PARPi veliparib (ABT888) in combination with cisplatin on the survival of three human oral cancer cell lines HSC-2, Ca9-22 and CAL27 and we observed the effects of ABT888 alone or in combination with cisplatin on apoptosis and DNA damage repair mechanism. The results obtained showed that ABT888 induces a cytotoxicity effect on cell viability increasing the apoptotic pathway as well as DNA strand break; moreover, our results displayed the effects with cisplatin in a dose-dependent manner. Therefore, our results indicate PARP inhibitors as adjuvants for therapeutic strategy of oral cancer.
T2-High Endotype and Response to Biological Treatments in Patients with Bronchiectasis
Authors: Oriano Martina , Gramegna Andrea , Amati Francesco , D’Adda Alice , Gaffuri Michele , Contoli Marco , Bindo Francesco , Simonetta Edoardo , Di Francesco Carlotta , Santambrogio Martina , Sotgiu Giovanni , Blasi Francesco , Aliberti Stefano
Published: July 2021

Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL−1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients’ clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.
Syndecan-4 in Tumor Cell Motility
Authors: Keller-Pinter Aniko , Gyulai-Nagy Szuzina , Becsky Daniel , Dux Laszlo , Rovo Laszlo
Published: July 2021

Syndecan-4 (SDC4) is a ubiquitously expressed, transmembrane proteoglycan bearing heparan sulfate chains. SDC4 is involved in numerous inside-out and outside-in signaling processes, such as binding and sequestration of growth factors and extracellular matrix components, regulation of the activity of the small GTPase Rac1, protein kinase C-alpha, the level of intracellular calcium, or the phosphorylation of focal adhesion kinase. The ability of this proteoglycan to link the extracellular matrix and actin cytoskeleton enables SDC4 to contribute to biological functions like cell adhesion and migration, cell proliferation, cytokinesis, cellular polarity, or mechanotransduction. The multiple roles of SDC4 in tumor pathogenesis and progression has already been demonstrated; therefore, the expression and signaling of SDC4 was investigated in several tumor types. SDC4 influences tumor progression by regulating cell proliferation as well as cell migration by affecting cell-matrix adhesion and several signaling pathways. Here, we summarize the general role of SDC4 in cell migration and tumor cell motility.
miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting CDKN1C, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs
Authors: Zhao Fangqing , Yang Zhongmin , Gu Xiaofan , Feng Lixing , Xu Mingshi , Zhang Xiongwen
Published: July 2021

Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance. This study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells. Knockdown of miR-92b-3p reversed the resistance of MDR HCT8/T cells to chemotherapeutic drugs in vitro and in vivo. Paclitaxel (PTX, a chemotherapy medication) could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. In studies on downstream molecules, results suggested that miR-92b-3p directly targeted Cyclin Dependent Kinase Inhibitor 1C (CDKN1C, which encodes a cell cycle inhibitor p57Kip2) to inhibit its expression and regulate the sensitivity of CRC cells to chemotherapeutic drugs. Mechanism study revealed that the miR-92b-3p/CDKN1C axis exerted a regulatory effect on the sensitivity of CRC cells via the regulation of cell cycle and apoptosis. In conclusion, these findings showed that miR-92b-3p/CDKN1C was an important regulator in the development of drug resistance in CRC cells, suggesting its potential application in drug resistance prediction and treatment.
Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications
Authors: Burgos-Ravanal Renato , Campos América , Díaz-Vesga Magda C. , González María Fernanda , León Daniela , Lobos-González Lorena , Leyton Lisette , Kogan Marcelo J. , Quest Andrew F. G.
Published: July 2021

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their “traits” to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as “cell competition”. This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as “the hallmarks of cancer” defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.
Chromatin and Epigenetic Dysregulation of Prostate Cancer Development, Progression, and Therapeutic Response
Authors: Kukkonen Konsta , Taavitsainen Sinja , Huhtala Laura , Uusi-Makela Joonas , Granberg Kirsi J. , Nykter Matti , Urbanucci Alfonso
Published: July 2021

The dysregulation of chromatin and epigenetics has been defined as the overarching cancer hallmark. By disrupting transcriptional regulation in normal cells and mediating tumor progression by promoting cancer cell plasticity, this process has the ability to mediate all defined hallmarks of cancer. In this review, we collect and assess evidence on the contribution of chromatin and epigenetic dysregulation in prostate cancer. We highlight important mechanisms leading to prostate carcinogenesis, the emergence of castration-resistance upon treatment with androgen deprivation therapy, and resistance to antiandrogens. We examine in particular the contribution of chromatin structure and epigenetics to cell lineage commitment, which is dysregulated during tumorigenesis, and cell plasticity, which is altered during tumor progression.
A New Anatomic and Staging-Oriented Classification of Radical Hysterectomy
Authors: Muallem Mustafa Zelal
Published: July 2021

The current understanding of radical hysterectomy more is centered on the uterus and little is being discussed about the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. This is because that the current classifications of radical hysterectomy are based only on the lateral extent of resection. This way is easier to be understood but does not reflect the anatomical and surgical conception of radical hysterectomy and the three-dimensional ways of tumour spreading, neither meet the need of adjusting the radicality according to the different stages of FIGO classification, which depends—at least in the early stages—on the tumour volume and the infiltration in the vagina (but not on the directly spread in the parametrium). The new classification presented in this paper does not base anymore on the lateral extent of resection only but too on the depth of resection in the small pelvic and the extent of the resected vaginal vault without or with its three-dimensional paracolpium. This classification takes into account the tumour size, stage, localization and infiltration in the vaginal vault and may offer the optimal tool to adjust and tailor the surgery according to these important variables.
Instruction of Immunometabolism by Adipose Tissue: Implications for Cancer Progression
Authors: Raja Remya , Wu Christopher , Limbeck Francesca , Butler Kristina , Acharya Abhinav P. , Curtis Marion
Published: July 2021

Disruption of metabolic homeostasis at the organismal level can cause metabolic syndrome associated with obesity. The role of adipose tissue in cancer has been investigated over the last several decades with many studies implicating obesity as a risk factor for the development of cancer. Adipose tissue contains a diverse array of immune cell populations that promote metabolic homeostasis through a tightly controlled balance of pro- and anti-inflammatory signals. During obesity, pro-inflammatory cell types infiltrate and expand within the adipose tissue, exacerbating metabolic dysfunction. Some studies have now shown that the intracellular metabolism of immune cells is also deregulated by the lipid-rich environment in obesity. What is not fully understood, is how this may influence cancer progression, metastasis, and anti-tumor immunity. This review seeks to highlight our current understanding of the effect of adipose tissue on immune cell function and discuss how recent results offer new insight into the role that adipose tissue plays in cancer progression and anti-tumor immunity.
Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer
Authors: Moraes João Alfredo , Encarnação Carol , Franco Victor Aguiar , Xavier Botelho Luiz Gabriel , Rodrigues Gabriella Pacheco , Ramos-Andrade Isadora , Barja-Fidalgo Christina , Renovato-Martins Mariana
Published: July 2021

Extracellular vesicles (EVs) are crucial elements that sustain the communication between tumor cells and their microenvironment, and have emerged as a widespread mechanism of tumor formation and metastasis. In obesity, the adipose tissue becomes hypertrophic and hyperplastic, triggering increased production of pro-inflammatory adipokines, such as tumor necrosis factor α, interleukin 6, interleukin 1, and leptin. Furthermore, obese adipose tissue undergoes dysregulation in the cargo content of the released EVs, resulting in an increased content of pro-inflammatory proteins, fatty acids, and oncogenic microRNAs. These alterations drive obesity-associated inflammatory responses both locally and systemically. After being ignored for a long time, adipose tissues have recently received considerable attention as a major player in tumor microenvironment-linked obesity and cancer. The role of adipose tissue in the establishment and progression of cancer is reinforced by its high plasticity and inflammatory content. Such a relationship may be established by direct contact between adipocytes and cancer cells within the microenvironment or systemically, via EV-mediated cell-to-cell communication. Here, we highlight cues evidencing the influence of adipose tissue-derived EVs on the hallmarks of cancer, which are critical for tumor malignancy.
Locoregional Treatments in Cholangiocarcinoma and Combined Hepatocellular Cholangiocarcinoma
Authors: Renzulli Matteo , Ramai Daryl , Singh Jameel , Sinha Samridhi , Brandi Nicolò , Ierardi Anna Maria , Albertini Elisa , Sacco Rodolfo , Facciorusso Antonio , Golfieri Rita
Published: July 2021

Cholangiocarcinoma (CCA) is a primary and aggressive cancer of the biliary tree. Combined hepatocellular cholangiocarcinoma (CHC) is a distinctive primary liver malignancy which has properties of both hepatocytic and cholangiocytic differentiation. CHC appears to have a worse prognosis compared to hepatocellular carcinoma, and similar to that of intrahepatic CCA. While significant advances have been made in understanding the pathophysiology and treatment of these two tumor types, their prognosis remains poor. Currently, liver resection is the primary treatment modality; however, only a minority of patients are eligible for surgery. However, the use of locoregional therapies proves an alternative approach to treating locally advanced disease with the aim of converting to resectability or even transplantation. Locoregional therapies such as transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), radiofrequency ablation (RFA), and photodynamic therapy (PDT) can provide patients with tumor control and increase the chances of survival. In this review, we appraise the evidence surrounding the use of locoregional therapies in treating patients with CCA and CHC.
The Mechanism of Rubisco Catalyzed Carboxylation Reaction: Chemical Aspects Involving Acid-Base Chemistry and Functioning of the Molecular Machine
Authors: Tommasi Immacolata C.
Published: July 2021

In recent years, a great deal of attention has been paid by the scientific community to improving the efficiency of photosynthetic carbon assimilation, plant growth and biomass production in order to achieve a higher crop productivity. Therefore, the primary carboxylase enzyme of the photosynthetic process Rubisco has received considerable attention focused on many aspects of the enzyme function including protein structure, protein engineering and assembly, enzyme activation and kinetics. Based on its fundamental role in carbon assimilation Rubisco is also targeted by the CO2-fertilization effect, which is the increased rate of photosynthesis due to increasing atmospheric CO2-concentration. The aim of this review is to provide a framework, as complete as possible, of the mechanism of the RuBP carboxylation/hydration reaction including description of chemical events occurring at the enzyme “activating” and “catalytic” sites (which involve Broensted acid-base reactions) and the functioning of the complex molecular machine. Important research results achieved over the last few years providing substantial advancement in understanding the enzyme functioning will be discussed.
Lymphatic Trafficking in the Eye: Modulation of Lymphatic Trafficking to Promote Corneal Transplant Survival
Authors: Hou Yanhong , Bock Felix , Hos Deniz , Cursiefen Claus
Published: July 2021

(Lymph)angiogenesis into the cornea prior to and after corneal transplantation is a critical risk factor for allograft rejection. Lymphatic vessels even more than blood vessels seem important in mediating immune responses, as they facilitate allograft sensitization in the draining lymph nodes. Thus, the concept of modulating lymphatic trafficking to promote corneal graft survival seems promising. A variety of approaches has been developed to inhibit progressive lymphangiogenesis in experimental settings. Recently, additionally to pharmacological approaches, clinically available techniques such as UVA-based corneal collagen crosslinking and fine needle diathermy were reported to be effective in regressing lymphatic vessels and to experimentally promote graft survival. Clinical pilot studies also suggest the efficacy of blocking antigen presenting cell trafficking to regional lymph nodes by regressing corneal lymphatic vessels to enhance allograft survival in high-risk eyes. In this article, we will give an overview of current strategies to modulate lymphatic trafficking with a special focus on recently reported strategies, which may be easy to translate into clinical practice. This novel concept of temporary, pretransplant regression of lymphatic vessels at the site of transplantation to promote subsequent corneal transplant survival (“lymphangioregressive preconditioning”) may also be applicable to other transplantation sites later.