bluuebunny/crossref_metadata_2025 huggingface dataset:
Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy
Authors: Yan Ranran , Liu Huayan , Lv Fang , Deng Yulin , Li Yujuan
Published: May 2021

The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell–cell junction and cell–extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.
Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives
Authors: Liu Szu-Yi , Tsai I-Ting , Hsu Yin-Chou
Published: May 2021

Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.
Increased Cuticle Waxes by Overexpression of WSD1 Improves Osmotic Stress Tolerance in Arabidopsis thaliana and Camelina sativa
Authors: Abdullah Hesham M. , Rodriguez Jessica , Salacup Jeffrey M. , Castañeda Isla S. , Schnell Danny J. , Pareek Ashwani , Dhankher Om Parkash
Published: May 2021

To ensure global food security under the changing climate, there is a strong need for developing ‘climate resilient crops’ that can thrive and produce better yields under extreme environmental conditions such as drought, salinity, and high temperature. To enhance plant productivity under the adverse conditions, we constitutively overexpressed a bifunctional wax synthase/acyl-CoA:diacylglycerol acyltransferase (WSD1) gene, which plays a critical role in wax ester synthesis in Arabidopsis stem and leaf tissues. The qRT-PCR analysis showed a strong upregulation of WSD1 transcripts by mannitol, NaCl, and abscisic acid (ABA) treatments, particularly in Arabidopsis thaliana shoots. Gas chromatography and electron microscopy analyses of Arabidopsis seedlings overexpressing WSD1 showed higher deposition of epicuticular wax crystals and increased leaf and stem wax loading in WSD1 transgenics compared to wildtype (WT) plants. WSD1 transgenics exhibited enhanced tolerance to ABA, mannitol, drought and salinity, which suggested new physiological roles for WSD1 in stress response aside from its wax synthase activity. Transgenic plants were able to recover from drought and salinity better than the WT plants. Furthermore, transgenics showed reduced cuticular transpirational rates and cuticle permeability, as well as less chlorophyll leaching than the WT. The knowledge from Arabidopsis was translated to the oilseed crop Camelina sativa (L.) Crantz. Similar to Arabidopsis, transgenic Camelina lines overexpressing WSD1 also showed enhanced tolerance to drought stress. Our results clearly show that the manipulation of cuticular waxes will be advantageous for enhancing plant productivity under a changing climate.
Functional and Material Properties in Nanocatalyst Design: A Data Handling and Sharing Problem
Authors: Lach Daniel , Zhdan Uladzislau , Smolinski Adam , Polanski Jaroslaw
Published: May 2021

(1) Background: Properties and descriptors are two forms of molecular in silico representations. Properties can be further divided into functional, e.g., catalyst or drug activity, and material, e.g., X-ray crystal data. Millions of real measured functional property records are available for drugs or drug candidates in online databases. In contrast, there is not a single database that registers a real conversion, TON or TOF data for catalysts. All of the data are molecular descriptors or material properties, which are mainly of a calculation origin. (2) Results: Here, we explain the reason for this. We reviewed the data handling and sharing problems in the design and discovery of catalyst candidates particularly, material informatics and catalyst design, structural coding, data collection and validation, infrastructure for catalyst design and the online databases for catalyst design. (3) Conclusions: Material design requires a property prediction step. This can only be achieved based on the registered real property measurement. In reality, in catalyst design and discovery, we can observe either a severe functional property deficit or even property famine.
Autonomic Nervous System in Obesity and Insulin-Resistance—The Complex Interplay between Leptin and Central Nervous System
Authors: Russo Benedetta , Menduni Marika , Borboni Patrizia , Picconi Fabiana , Frontoni Simona
Published: May 2021

The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated.
Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier
Authors: Bakalarz Dominik , Korbut Edyta , Yuan Zhengnan , Yu Bingchen , Wójcik Dagmara , Danielak Aleksandra , Magierowska Katarzyna , Kwiecień Slawomir , Brzozowski Tomasz , Marcinkowska Monika , Wang Binghe , Magierowski Marcin
Published: May 2021

Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.
Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases
Authors: Kamagata Koji , Andica Christina , Kato Ayumi , Saito Yuya , Uchida Wataru , Hatano Taku , Lukies Matthew , Ogawa Takashi , Takeshige-Amano Haruka , Akashi Toshiaki , Hagiwara Akifumi , Fujita Shohei , Aoki Shigeki
Published: May 2021

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.
Sensitivity of Intra- and Intermolecular Interactions of Benzo[h]quinoline from Car–Parrinello Molecular Dynamics and Electronic Structure Inspection
Authors: Panek Jarosław J. , Zasada Joanna , Szyja Bartłomiej M. , Kizior Beata , Jezierska Aneta
Published: May 2021

The O-H...N and O-H...O hydrogen bonds were investigated in 10-hydroxybenzo[h]quinoline (HBQ) and benzo[h]quinoline-2-methylresorcinol complex in vacuo, solvent and crystalline phases. The chosen systems contain analogous donor and acceptor moieties but differently coupled (intra- versus intermolecularly). Car–Parrinello molecular dynamics (CPMD) was employed to shed light onto principle components of interactions responsible for the self-assembly. It was applied to study the dynamics of the hydrogen bonds and vibrational features as well as to provide initial geometries for incorporation of quantum effects and electronic structure studies. The vibrational features were revealed using Fourier transformation of the autocorrelation function of atomic velocity and by inclusion of nuclear quantum effects on the O-H stretching solving vibrational Schrödinger equation a posteriori. The potential of mean force (Pmf) was computed for the whole trajectory to derive the probability density distribution and for the O-H stretching mode from the proton vibrational eigenfunctions and eigenvalues incorporating statistical sampling and nuclear quantum effects. The electronic structure changes of the benzo[h]quinoline-2-methylresorcinol dimer and trimers were studied based on Constrained Density Functional Theory (CDFT) whereas the Electron Localization Function (ELF) method was applied for all systems. It was found that the bridged proton is localized on the donor side in both investigated systems in vacuo. The crystalline phase simulations indicated bridged proton-sharing and transfer events in HBQ. These effects are even more pronounced when nuclear quantization is taken into account, and the quantized Pmf allows the proton to sample the acceptor area more efficiently. The CDFT indicated the charge depletion at the bridged proton for the analyzed dimer and trimers in solvent. The ELF analysis showed the presence of the isolated proton (a signature of the strongest hydrogen bonds) only in some parts of the HBQ crystal simulation. The collected data underline the importance of the intramolecular coupling between the donor and acceptor moieties.
Measuring Awareness of Social Engineering in the Educational Sector in the Kingdom of Saudi Arabia
Authors: Alsulami Majid H. , Alharbi Fawaz D. , Almutairi Hamdan M. , Almutairi Bandar S. , Alotaibi Mohammed M. , Alanzi Majdi E. , Alotaibi Khaled G. , Alharthi Sultan S.
Published: May 2021

Social engineering is one of the most inventive methods of gaining unauthorized access to information systems and obtaining sensitive information. This type of cybersecurity threat requires minimal technical knowledge because it relies on the organization’s human element. Social engineers use various techniques, such as phishing, to manipulate users into either granting them access to various systems or disclosing their private data and information. Social engineering attacks can cost organizations more than 100,000 USD per instance. Therefore, it is necessary for organizations to increase their users’ awareness of social engineering attacks to mitigate the problem. The aim of this study is to provide a measurement of social engineering awareness in the Saudi educational sector. To achieve the aim of this study, a questionnaire was developed and evaluated. A total of 465 respondents completed the survey and answered questions related to measuring their knowledge of social engineering. The results show that 34% of participants (158 participants) had previous knowledge of social engineering approaches. The results also indicate that there are significant differences between participants with prior knowledge of social engineering and those with no such knowledge in terms of their security practices and skills. The implication of this study is that training is an essential factor in increasing the awareness of social engineering attacks in the Saudi educational sector.
Ensemble Models Predict Invasive Bee Habitat Suitability Will Expand under Future Climate Scenarios in Hawai’i
Authors: Tabor Jesse A. , Koch Jonathan B.
Published: May 2021

Climate change is predicted to increase the risk of biological invasions by increasing the availability of climatically suitable regions for invasive species. Endemic species on oceanic islands are particularly sensitive to the impact of invasive species due to increased competition for shared resources and disease spread. In our study, we used an ensemble of species distribution models (SDM) to predict habitat suitability for invasive bees under current and future climate scenarios in Hawai’i. SDMs projected on the invasive range were better predicted by georeferenced records from the invasive range in comparison to invasive SDMs predicted by records from the native range. SDMs estimated that climatically suitable regions for the eight invasive bees explored in this study will expand by ~934.8% (±3.4% SE). Hotspots for the invasive bees are predicted to expand toward higher elevation regions, although suitable habitat is expected to only progress up to 500 m in elevation in 2070. Given our results, it is unlikely that invasive bees will interact directly with endemic bees found at >500 m in elevation in the future. Management and conservation plans for endemic bees may be improved by understanding how climate change may exacerbate negative interactions between invasive and endemic bee species.
High Flow Oxygen Therapy at Two Initial Flow Settings versus Conventional Oxygen Therapy in Cardiac Surgery Patients with Postextubation Hypoxemia: A Single-Center, Unblinded, Randomized, Controlled Trial
Authors: Theologou Stavros , Ischaki Eleni , Zakynthinos Spyros G. , Charitos Christos , Michopanou Nektaria , Patsatzis Stratos , Mentzelopoulos Spyros D.
Published: May 2021

In cardiac surgery patients with pre-extubation PaO2/inspired oxygen fraction (FiO2) < 200 mmHg, the possible benefits and optimal level of high-flow nasal cannula (HFNC) support are still unclear; therefore, we compared HFNC support with an initial gas flow of 60 or 40 L/min and conventional oxygen therapy. Ninety nine patients were randomly allocated (respective ratio: 1:1:1) to I = intervention group 1 (HFNC initial flow = 60 L/min, FiO2 = 0.6), intervention group 2 (HFNC initial flow = 40 L/min, FiO2 = 0.6), or control group (Venturi mask, FiO2 = 0.6). The primary outcome was occurrence of treatment failure. The baseline characteristics were similar. The hazard for treatment failure was lower in intervention group 1 vs. control (hazard ratio (HR): 0.11, 95% CI: 0.03–0.34) and intervention group 2 vs. control (HR: 0.30, 95% CI: 0.12–0.77). During follow-up, the probability of peripheral oxygen saturation (SpO2) > 92% and respiratory rate within 12–20 breaths/min was 2.4–3.9 times higher in intervention group 1 vs. the other 2 groups. There was no difference in PaO2/FiO2, patient comfort, intensive care unit or hospital stay, or clinical course complications or adverse events. In hypoxemic cardiac surgery patients, postextubation HFNC with an initial gas flow of 60 or 40 L/min resulted in less frequent treatment failure vs. conventional therapy. The results in terms of SpO2/respiratory rate targets favored an initial HFNC flow of 60 L/min.
Clinical and Forensic Aspects of the Different Subtypes of Argyria
Authors: Mota Luís , Dinis-Oliveira Ricardo Jorge
Published: May 2021

Argyria encompasses the different cosmetic alterations that can develop if enough silver particles deposit in a specific tissue, typically in the skin, ranging from localized dark-blue macules to a generalized slate-gray/bluish tinge following systemic absorption. This work aims to fully review the state of the art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic features of argyria. Argyria has been diagnosed in a wide range of ages, both sexes and varied ethnicities, with no known individual predisposing factors. Ultraviolet radiation with subsequence increases of melanin production aggravates the discoloration due to a reduction in the silver deposits. Physical examination and silver exposure in the anamnesis can be highly suggestive of the diagnosis, but a histopathological analysis with Energy-Dispersive X-ray Spectroscopy is required to unequivocally determine the discoloration etiology. Safe and effective treatment has only been accomplished with laser techniques, though only a few cases have been reported and with limited follow-up time. In conclusion, argyria typically has an occupational or iatrogenic etiology. It should be suspected when a patient presents with typical skin or eye lesions. A seemingly viable treatment modality, with laser technology, is finally within the horizon.
Myocardial Injury in COVID-19 Patients: Association with Inflammation, Coagulopathy and In-Hospital Prognosis
Authors: Arévalos Victor , Ortega-Paz Luis , Rodríguez-Arias Juan José , Calvo Margarita , Castrillo Leticia , Salazar Anthony , Roque Merce , Dantas Ana Paula , Sabaté Manel , Brugaletta Salvatore
Published: May 2021

The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4–7) vs. 2 (1–4), p = 0.001), higher CRP values (18.3 (9.6–25.9) mg/dL vs. 12.0 (5.4–19.4) mg/dL, p ˂ 0.001) and CAC score (1 (0–2) vs. 0 (0–1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.
Multi-Omics Analysis of Anti-Inflammatory Action of Alkaline Extract of the Leaves of Sasa sp.
Authors: Sakagami Hiroshi , Nakatani Sachie , Enomoto Ayame , Ota Sana , Kaneko Miku , Sugimoto Masahiro , Horiuchi Misaki , Toeda Kazuki , Oizumi Takaaki
Published: May 2021

Efficient utilization of alkaline extracts of several plants for the treatment of oral diseases has been reported. To investigate the mechanism of anti-inflammatory activity of alkaline extract of the leaves of Sasa sp. (SE), multi-omics analysis using metabolomics and DNA array was performed. Human gingival fibroblasts (HGFs) were treated for IL-1β to induce inflammation (detected by PGE2 production in culture medium) in the presence or absence of SE. Both IL-1β and SE showed slight hormetic growth stimulation against HGF. SE inhibited PGE2 production dose- and time-dependently. Its inhibitory action was more pronounced by first treating the cells with SE, rather than with IL-1β. At 3 h after IL-1β treatment, 18 amino acids (except cysteine and glutamic acid), total glutathione (GSH, GSSG, Cys-GSH disulfide), Met-sulfoxide, 5-oxoproline, and SAM declined, whereas DNA expressions of AKT, CASP3, and CXCL3 were elevated. These changes were reversed by simultaneous treatment with SE. The present study suggests that the anti-inflammatory action of SE is mediated via various metabolic pathways for cell survival, apoptosis, and leukocyte recruitment.
Positive Impact of Levothyroxine Treatment on Pregnancy Outcome in Euthyroid Women with Thyroid Autoimmunity Affected by Recurrent Miscarriage
Authors: Dal Lago Alessandro , Galanti Francesco , Miriello Donatella , Marcoccia Antonella , Massimiani Micol , Campagnolo Luisa , Moretti Costanzo , Rago Rocco
Published: May 2021

Impaired thyroid hormone availability during early pregnancy is associated with recurrent miscarriage (RM) and adverse pregnancy outcomes. The main cause of thyroid dysfunction is thyroid-related autoimmunity (TAI), characterized by a significantly higher serum level of thyroid-stimulating hormone (TSH) compared to that of women without thyroid autoimmunity. TAI is associated with a significantly increased risk of miscarriage, and the incidence of TAI in women experiencing RM is higher compared to normal fertile women. In the present study, we have performed a retrospective analysis comparing the ability to conceive, the number of miscarriages and full-term pregnancies between 227 euthyroid women with autoimmune thyroid disease affected by RM and treated with levothyroxine (LT4) as adjuvant therapy, and a control group of 230 untreated women. We have observed a significant improvement of full-term pregnancies in treated women (59%) compared to untreated women (13%, p < 0.0001). Compared to the control group, treated women had a lower percentage of miscarriages (12% vs. 30%) and improved capacity to conceive (57% vs. 29%). Using age as a variable, the outcome in women younger than 35 years was not influenced by the LT4 therapy. Whereas, in women over 35 years, supplementation with LT4 significantly reduced the miscarriage rate (p < 0.05). We can conclude that a transient impairment of TH availability, not easily detectable before pregnancy, could be an important cause of RM in a subset of euthyroid women with autoimmune thyroid disease. This transient impairment may be reverted using adjuvant treatment with low doses of LT4.
Current Therapy of the Patients with MDS: Walking towards Personalized Therapy
Authors: Palacios-Berraquero Maria Luisa , Alfonso-Piérola Ana
Published: May 2021

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia and peripheral cytopenias. Nowadays, MDS therapy is selected based on risk. The goals of therapy are different in low-risk and high-risk patients. In low-risk MDS, the goal is to decrease transfusion needs and to increase the quality of life. Currently, available drugs for newly diagnosed low-risk MDS include growth factor support, lenalidomide and immunosuppressive therapy. Additionally, luspatercept has recently been added to treat patients with MDS with ring sideroblasts, who are not candidates or have lost the response to erythropoiesis-stimulating agents. Treatment of high-risk patients is aimed to improve survival. To date, the only currently approved treatments are hypomethylating agents and allogeneic stem cell transplantation. However, the future for MDS patients is promising. In recent years, we are witnessing the emergence of multiple treatment combinations based on hypomethylating agents (pevonedistat, magrolimab, eprenetapopt, venetoclax) that have proven to be effective in MDS, even those with high-risk factors. Furthermore, the approval in the US of an oral hypomethylating agent opens the door to exclusively oral combinations for these patients and their consequent impact on the quality of life of these patients. Relapsed and refractory patients remain an unmet clinical need. We need more drugs and clinical trials for this profile of patients who have a dismal prognosis.
Liquid Biopsy: A New Tool for Overcoming CDKi Resistance Mechanisms in Luminal Metastatic Breast Cancer
Authors: González-Conde Miriam , Yañez-Gómez Celso , López-López Rafael , Costa Clotilde
Published: May 2021

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2− BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi), in combination with an aromatase inhibitor or fulvestrant, have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2− metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all of the patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms that underlie this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease, and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We mainly focus on those studies that describe the possible resistance mechanisms in circulating tumour-derived material.
The Impacts of Self-Construal and Perceived Risk on Technology Readiness
Authors: Choi Jaeun , Yoo Dongho
Published: May 2021

This paper explores how different self-construals interact with perceived risk and influence tourism consumers’ technology readiness toward tourism mobile apps. The study used 284 tourist participants to show that tourism consumers, regardless of self-construal type, have a negative perception of technology readiness when they perceive a high level of risk. Furthermore, those with independent self-construal have a more positive perception of technology readiness than those with an interdependent self-construal when they perceive a low level of risk. The results also show that technology readiness mediates the relationship between self-construal and use intention toward mobile apps. Based on these results, we proposed the following practical implications. First, companies need to find and lower potential risks that can be perceived in tourism mobile apps. They must also deliver different messages according to consumers’ self-construal. Companies should provide independents with information related to the positive benefits obtained through the mobile app, and interdependents should be provided with information that reduces perceived losses.
Corrosion of Steel Rebars in Anoxic Environments. Part I: Electrochemical Measurements
Authors: Garcia Elena , Torres Julio , Rebolledo Nuria , Arrabal Raul , Sanchez Javier
Published: May 2021

The number of reinforced concrete structures subject to anoxic conditions such as offshore platforms and geological storage facilities is growing steadily. This study explored the behaviour of embedded steel reinforcement corrosion under anoxic conditions in the presence of different chloride concentrations. Corrosion rate values were obtained by three electrochemical techniques: Linear polarization resistance, electrochemical impedance spectroscopy, and chronopotenciometry. The corrosion rate ceiling observed was 0.98 µA/cm2, irrespective of the chloride content in the concrete. By means of an Evans diagram, it was possible to estimate the value of the cathodic Tafel constant (bc) to be 180 mV dec−1, and the current limit yielded an ilim value of 0.98 µA/cm2. On the other hand, the corrosion potential would lie most likely in the −900 mVAg/AgCl to −1000 mVAg/AgCl range, whilst the bounds for the most probable corrosion rate were 0.61 µA/cm2 to 0.22 µA/cm2. The experiments conducted revealed clear evidence of corrosion-induced pitting that will be assessed in subsequent research.
Promising Technological and Industrial Applications of Deep Eutectic Systems
Authors: Mannu Alberto , Blangetti Marco , Baldino Salvatore , Prandi Cristina
Published: May 2021

Deep Eutectic Systems (DESs) are obtained by combining Hydrogen Bond Acceptors (HBAs) and Hydrogen Bond Donors (HBDs) in specific molar ratios. Since their first appearance in the literature in 2003, they have shown a wide range of applications, ranging from the selective extraction of biomass or metals to medicine, as well as from pollution control systems to catalytic active solvents and co-solvents. The very peculiar physical properties of DESs, such as the elevated density and viscosity, reduced conductivity, improved solvent ability and a peculiar optical behavior, can be exploited for engineering modular systems which cannot be obtained with other non-eutectic mixtures. In the present review, selected DESs research fields, as their use in materials synthesis, as solvents for volatile organic compounds, as ingredients in pharmaceutical formulations and as active solvents and cosolvents in organic synthesis, are reported and discussed in terms of application and future perspectives.
Novel Approaches to the Design of an Ultra-Fast Magnetorheological Valve for Semi-Active Control
Authors: Strecker Zbyněk , Jeniš Filip , Kubík Michal , Macháček Ondřej , Choi Seung-Bok
Published: May 2021

This article presents a list of suitable techniques and materials leading to the design of an ultra-fast magnetorheological (MR) valve. Two approaches for achieving the short response time are proposed: (a) by means of material, and (b) by means of the shape. Within the shape approach, the revolutionary technique of 3D metal printing using a selective laser melting (SLM) method was tested. The suitability of the materials and techniques is addressed based on the length of the response time, which is determined by the FEM. The simulation results determine the response time of the magnetic flux density on the step signal of the current. Subsequently, the response time is verified by the measurement of the simple magnetorheological valve. The following materials were tested: martensitic stainless steel AISI 420A (X20Cr13), cutting steel 11SMn30, pure iron for SLM, Sintex SMC STX prototyping material, ferrite N87, and Vacoflux 50. A special technique involving grooves was used for preventing eddy currents on materials with a high electrical conductivity. The simulation and experimental results indicate that a response time shorter than 2.5 ms can be achieved using materials such as Sintex SMC prototyping, ferrite N87, and grooved variants of metal pistons.
Repair of a Cracked Historic Maryan Bell by Gas Welding
Authors: Bartocha Dariusz , Baron Czesław
Published: May 2021

In this article, the range of works connected with the repair of a historical Maryan bell from 1639 are presented. The first attempts to repair damaged bells occurred in the 1930s in Poland. However, this process was stopped because of extensive technological difficulties. Welding and soldering-welding were the basic methods. There is one difference between these two methods—connecting surfaces are melted during the welding process but only heated until the melting temperature of the material added to the connection (that is the solder) during the soldering-welding process. It was important to heat the bell to the proper temperature during welding. Uneven heating causes the enlargement of existing cracks or the appearance of new ones, or even the complete destruction of the bell. Nowadays, a method of even heating using a special heating mat has been devised. Thanks to this method it is possible to control the heating and cooling process. The most important task during the whole operation of bell welding was obtaining the original sound. During this research, the chemical composition was examined to prepare a welding rod with a suitable chemical composition. After the repair process, an analysis of the sound of the bell was conducted. It was shown that the repair of bells is possible when correct thermal parameters are used. The most highly recommended technique for repairing bells is gas welding.
Black TiOx Films with Photothermal-Assisted Photocatalytic Activity Prepared by Reactive Sputtering
Authors: Mao Quan , Liu Meng , Li Yajie , Wei Yuquan , Yang Yong , Huang Zhengren
Published: May 2021

Titanium oxide is widely applied as a photocatalyst. However, its low efficiency and narrow light absorption range are two main disadvantages that severely impede its practical application. In this work, black TiOx films with different chemical compositions were fabricated by tuning target voltage and controlling O2 flow during reactive DC magnetron sputtering. The optimized TiOx films with mixed phases (TiO, Ti2O3, Ti3O5, and TiO2) exhibited fantastic photothermal and photocatalytic activity by combining high light-absorptive Ti2O3 and Ti3O5 phases with the photocatalytic TiO2 phase. The sample prepared with oxygen flow at 5.6 ± 0.2 sccm and target voltage near 400 V exhibited excellent optical absorbance of 89.29% under visible light, which could improve surface temperature to 114 °C under sunlight. This film could degrade Rhodamine-B up to 74% after 150 min of UV irradiation. In a word, this work provides a guideline for fabricating black TiOx films with photothermal-assisted photocatalytic activity by reactive DC magnetron sputtering, which could avoid the usage of hydrogen and is convenient for quantity preparation.
Tribological and Thermo-Mechanical Properties of TiO2 Nanodot-Decorated Ti3C2/Epoxy Nanocomposites
Authors: Zhang Yalin , He Xuzhao , Cao Miao , Shen Xiaojun , Yang Yaru , Yi Jie , Guan Jipeng , Shen Jianxiang , Xi Man , Zhang Yuanjie , Tang Bolin
Published: May 2021

The micromorphology of fillers plays an important role in tribological and mechanical properties of polymer matrices. In this work, a TiO2-decorated Ti2C3 (TiO2/Ti3C2) composite particle with unique micro-nano morphology was engineered to improve the tribological and thermo-mechanical properties of epoxy resin. The TiO2/Ti3C2 were synthesized by hydrothermal growth of TiO2 nanodots onto the surface of accordion-like Ti3C2 microparticles, and three different decoration degrees (low, medium, high density) of TiO2/Ti3C2 were prepared by regulating the concentration of TiO2 precursor solution. Tribological test results indicated that the incorporation of TiO2/Ti3C2 can effectively improve the wear rate of epoxy resin. Among them, the medium density TiO2/Ti3C2/epoxy nanocomposites gained a minimum wear rate. This may be ascribed by the moderate TiO2 nanodot protuberances on the Ti3C2 surface induced a strong mechanical interlock effect between medium-density TiO2/Ti3C2 and the epoxy matrix, which can bear a higher normal shear stress during sliding friction. The morphologies of worn surfaces and wear debris revealed that the wear form was gradually transformed from fatigue wear in neat epoxy to abrasive wear in TiO2/Ti3C2/epoxy nanocomposites. Moreover, the results of thermo-mechanical property indicated that incorporation of TiO2/Ti3C2 also effectively improved the storage modulus and glass transition temperature of epoxy resin.
The Impact of a Mobile Shading System and a Phase-Change Heat Store on the Thermal Functioning of a Transparent Building Partition
Authors: Musiał Michał , Lichołai Lech
Published: May 2021

The article presents the results of multi-month field tests and numerical analyses describing the thermal functioning of mobile shading systems for building windows containing a phase-change heat accumulator. The experiments were conducted in the summer period with temperate climate conditions in Rzeszów (Poland). The tested shading system was dedicated to the daily life cycle of residents, taking into account both the need to illuminate the rooms with natural light and reducing the undesirable overheating of the rooms in the summer. The obtained empirical results showed a reduction in room overheating in the summer period by 29.4% from composite windows with a phase-change heat accumulator and a mobile shading system as compared to the reference composite window with an analogous mobile shading system. The database of empirical results allowed for the creation and verification of a numerical model of heat conversion, storage and distribution within the composite window containing phase change material and a mobile shading system. The verified model made it possible to analyse the thermal functioning of the modified transparent partitions in cool temperate, temperate and subtropical climates. The article is a solution to the problem of undesirable overheating of transparent building partitions by efficient storage and distribution of solar radiation energy thanks to the use of a mobile shading system and a phase change material, while presenting a useful tool enabling the prediction of energy gains in different climatic conditions.
Microstructure and Magnetic Field-Induced Strain of a Ni-Mn-Ga-Co-Gd High-Entropy Alloy
Authors: Ju Jia , Hu Liang , Bao Chenwei , Shuai Liguo , Yan Chen , Wang Zhirong
Published: May 2021

The effect of a high-entropy design on martensitic transformation and magnetic field-induced strain has been investigated in the present study for Ni-Mn-Ga-Co-Gd ferromagnetic shape-memory alloys. The purpose was to increase the martensitic transition temperature, as well as the magnetic field-induced strain, of these materials. The results show that there is a co-existence of β, γ, and martensite phases in the microstructure of the alloy samples. Additionally, the martensitic transformation temperature shows a markedly increasing trend for these high-entropy samples, with the largest value being approximately 500 °C. The morphology of the martensite exhibits typical twin characteristics of type L10. Moreover, the magnetic field-induced strain shows an increasing trend, which is caused by the driving force of the twin martensite re-arrangement strengthening.
Zeolite NaP1 Functionalization for the Sorption of Metal Complexes with Biodegradable N-(1,2-dicarboxyethyl)-D,L-aspartic Acid
Authors: Kołodyńska Dorota , Ju Yongming , Franus Małgorzata , Franus Wojciech
Published: May 2021

The possibility of application of chitosan-modified zeolite as sorbent for Cu(II), Zn(II), Mn(II), and Fe(III) ions and their mixtures in the presence of N-(1,2-dicarboxyethyl)-D,L-aspartic acid, IDHA) under different experimental conditions were investigated. Chitosan-modified zeolite belongs to the group of biodegradable complexing agents used in fertilizer production. NaP1CS as a carrier forms a barrier to the spontaneous release of the fertilizer into soil. The obtained materials were characterized by Fourier transform infrared spectroscopy (FTIR); surface area determination (ASAP); scanning electron microscopy (SEM-EDS); X-ray fluorescence (XRF); X-ray diffraction (XRD); and carbon, hydrogen, and nitrogen (CHN), as well as thermogravimetric (TGA) methods. The concentrations of Cu(II), Zn(II), Mn(II), and Fe(III) complexes with IDHA varied from 5–20 mg/dm3 for Cu(II), 10–40 mg/dm3 for Fe(III), 20–80 mg/dm3 for Mn(II), and 10–40 mg/dm3 for Zn(II), respectively; pH value (3–6), time (1–120 min), and temperature (293–333 K) on the sorption efficiency were tested. The Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin adsorption models were applied to describe experimental data. The pH 5 proved to be appropriate for adsorption. The pseudo-second order and Langmuir models were consistent with the experimental data. The thermodynamic parameters indicate that adsorption is spontaneous and endothermic. The highest desorption percentage was achieved using the HCl solution, therefore, proving that method can be used to design slow-release fertilizers.
Magnetization of Ultraviolet-Reduced Graphene Oxide Flakes in Composites Based on Polystyrene
Authors: Ionov Alexander N. , Volkov Mikhail P. , Nikolaeva Marianna N. , Smyslov Ruslan Y. , Bugrov Alexander N.
Published: May 2021

This work presents our study results of the magnetization of multilayer UV-reduced graphene oxide (UV-rGO), polymer matrix (polystyrene), and a conjugated composite based on them. The mesoscopic structure of the composites synthesized in this work was studied by such methods as X-ray diffraction, SEM, as well as NMR-, IR- and Raman spectroscopy. The magnetization of the composites under investigation and their components was measured using a vibrating-sample magnetometer. It has been shown that the UV-reduction process leads to the formation of many submicron holes distributed inside rGO flakes, which can create edge defects, causing possibly magnetic order in the graphite samples under investigation on the mesoscopic level. This article provides an alternative explanation for the ferromagnetic hysteresis loop in UV-rGO on the base of superconductivity type-II.
Disassembly Study of Ultrasonically Welded Thermoplastic Composite Joints via Resistance Heating
Authors: Frederick Harry , Li Wencai , Palardy Genevieve
Published: May 2021

This manuscript explores the disassembly potential of ultrasonically welded thermoplastic composite joints for reuse or recycling through resistance heating via a nanocomposite film located at the welded interface. Nanocomposite films containing multi-walled carbon nanotubes (MWCNTs) were characterized for thermo-electrical behavior to assess self-heating. It was generally observed that maximum temperature increased with MWCNT and film thickness. To demonstrate potential for disassembly, glass fiber/polypropylene adherends were welded with nanocomposite films. Shear stress during disassembly was measured for three initial adherend’s surface temperatures. It was found that the required tensile load decreased by over 90% at the highest temperatures, effectively demonstrating the potential for disassembly via electrically conductive films. Fracture surfaces suggested that disassembly was facilitated through a combination of nanocomposite and matrix melting and weakened fiber–matrix interface. Limitations, such as slow heating rates and the loss of contact at the interface, imply that the method could be more suited for recycling, instead of repair and reuse, as the heat-affected zone extended through the adherends’ thickness at the overlap during heating.
Main 3D Manufacturing Techniques for Customized Bone Substitutes. A Systematic Review
Authors: Montero Javier , Becerro Alicia , Pardal-Peláez Beatriz , Quispe-López Norberto , Blanco Juan-Francisco , Gómez-Polo Cristina
Published: May 2021

Clinicians should be aware of the main methods and materials to face the challenge of bone shortage by manufacturing customized grafts, in order to repair defects. This study aims to carry out a bibliographic review of the existing methods to manufacture customized bone scaffolds through 3D technology and to identify their current situation based on the published papers. A literature search was carried out using “3D scaffold”, “bone regeneration”, “robocasting” and “3D printing” as descriptors. This search strategy was performed on PubMed (MEDLINE), Scopus and Cochrane Library, but also by hand search in relevant journals and throughout the selected papers. All the papers focusing on techniques for manufacturing customized bone scaffolds were reviewed. The 62 articles identified described 14 techniques (4 subtraction + 10 addition techniques). Scaffold fabrication techniques can be also be classified according to the time at which they are developed, into Conventional techniques and Solid Freeform Fabrication techniques. The conventional techniques are unable to control the architecture of the pore and the pore interconnection. However, current Solid Freeform Fabrication techniques allow individualizing and generating complex geometries of porosity. To conclude, currently SLA (Stereolithography), Robocasting and FDM (Fused deposition modeling) are promising options in customized bone regeneration.