bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis
Authors: Buono Lola , Scalabrin Simona , De Iuliis Marco , Tanzi Adele , Grange Cristina , Tapparo Marta , Nuzzi Raffaele , Bussolati Benedetta
Published: May 2021

Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy.
Effects of Thrombomodulin in Reducing Lethality and Suppressing Neutrophil Extracellular Trap Formation in the Lungs and Liver in a Lipopolysaccharide-Induced Murine Septic Shock Model
Authors: Kato Yu , Nishida Osamu , Kuriyama Naohide , Nakamura Tomoyuki , Kawaji Takahiro , Onouchi Takanori , Hasegawa Daisuke , Shimomura Yasuyo
Published: May 2021

Neutrophil extracellular trap (NET) formation, an innate immune system response, is associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the exacerbation of sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. We have previously reported that recombinant human soluble thrombomodulin (rTM) reduces lipopolysaccharide (LPS)-induced NET formation in vitro. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. Mice were injected intraperitoneally (i.p.) with 10 mg/kg LPS. rTM (6 mg/kg/day) or saline was administered i.p. 1 h after LPS injection. In the LPS-induced murine septic shock model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, the serum cytokine (interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage chemotactic protein-1 (MCP-1), and interleukin-10 (IL-10)) levels were increased. The administration of rTM in this model prevented NET formation in the organs and suppressed the increase in the levels of all cytokines except IL-1β. Furthermore, the survival rate improved. We provide a novel role of TM in treating inflammation and NETs in organs during sepsis.
Effect of Cerenkov Radiation-Induced Photodynamic Therapy with 18F-FDG in an Intraperitoneal Xenograft Mouse Model of Ovarian Cancer
Authors: Chen Yi-An , Li Jia-Je , Lin Syue-Liang , Lu Cheng-Hsiu , Chiu Sain-Jhih , Jeng Fong-Shya , Chang Chi-Wei , Yang Bang-Hung , Chang Ming-Cheng , Ke Chien-Chih , Liu Ren-Shyan
Published: May 2021

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.
Anaphylaxis: Focus on Transcription Factor Activity
Authors: Guo Yanru , Proaño-Pérez Elizabeth , Muñoz-Cano Rosa , Martin Margarita
Published: May 2021

Anaphylaxis is a severe allergic reaction, rapid in onset, and can lead to fatal consequences if not promptly treated. The incidence of anaphylaxis has risen at an alarming rate in past decades and continues to rise. Therefore, there is a general interest in understanding the molecular mechanism that leads to an exacerbated response. The main effector cells are mast cells, commonly triggered by stimuli that involve the IgE-dependent or IgE-independent pathway. These signaling pathways converge in the release of proinflammatory mediators, such as histamine, tryptases, prostaglandins, etc., in minutes. The action and cell targets of these proinflammatory mediators are linked to the pathophysiologic consequences observed in this severe allergic reaction. While many molecules are involved in cellular regulation, the expression and regulation of transcription factors involved in the synthesis of proinflammatory mediators and secretory granule homeostasis are of special interest, due to their ability to control gene expression and change phenotype, and they may be key in the severity of the entire reaction. In this review, we will describe our current understanding of the pathophysiology of human anaphylaxis, focusing on the transcription factors’ contributions to this systemic hypersensitivity reaction. Host mutation in transcription factor expression, or deregulation of their activity in an anaphylaxis context, will be updated. So far, the risk of anaphylaxis is unpredictable thus, increasing our knowledge of the molecular mechanism that leads and regulates mast cell activity will enable us to improve our understanding of how anaphylaxis can be prevented or treated.
Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction—Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage
Authors: Janjusevic Milijana , Fluca Alessandra Lucia , Ferro Federico , Gagno Giulia , D’Alessandra Yuri , Beltrami Antonio Paolo , Sinagra Gianfranco , Aleksova Aneta
Published: May 2021

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic HF. Traditional biomarkers are very useful as diagnostic and prognostic tools in the cardiovascular field; however, their application is usually limited to overt cardiac disease. On the other hand, a growing number of studies is investigating the diagnostic and prognostic potential of new biomarkers, such as micro-RNAs (miRNA), long non-coding RNAs, and exosome cargo, because of their involvement in the early phases of cardiac dysfunction. Unfortunately, their use in asymptomatic phases remains a distant goal. The aim of this review is to gather the current knowledge of old and novel biomarkers in the early diagnosis of cardiac dysfunction in asymptomatic individuals.
Gadolinium Protects Arabidopsis thaliana against Botrytis cinerea through the Activation of JA/ET-Induced Defense Responses
Authors: Batista-Oliveira Juliana Santos , Formey Damien , Torres Martha , Aragón Wendy , Romero-Contreras Yordan Jhovani , Maruri-López Israel , Tromas Alexandre , Schwan-Estrada Kátia Regina Freitas , Serrano Mario
Published: May 2021

Plant food production is severely affected by fungi; to cope with this problem, farmers use synthetic fungicides. However, the need to reduce fungicide application has led to a search for alternatives, such as biostimulants. Rare-earth elements (REEs) are widely used as biostimulants, but their mode of action and their potential as an alternative to synthetic fungicides have not been fully studied. Here, the biostimulant effect of gadolinium (Gd) is explored using the plant-pathosystem Arabidopsis thaliana–Botrytis cinerea. We determine that Gd induces local, systemic, and long-lasting plant defense responses to B. cinerea, without affecting fungal development. The physiological changes induced by Gd have been related to its structural resemblance to calcium. However, our results show that the calcium-induced defense response is not sufficient to protect plants against B. cinerea, compared to Gd. Furthermore, a genome-wide transcriptomic analysis shows that Gd induces plant defenses and modifies early and late defense responses. However, the resistance to B. cinerea is dependent on JA/ET-induced responses. These data support the conclusion that Gd can be used as a biocontrol agent for B. cinerea. These results are a valuable tool to uncover the molecular mechanisms induced by REEs.
Probiotics, Photobiomodulation, and Disease Management: Controversies and Challenges
Authors: Ailioaie Laura , Litscher Gerhard
Published: May 2021

In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.
Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa
Authors: Antonelli Giada , Cappelli Luigia , Cinelli Paolo , Cuffaro Rossella , Manca Benedetta , Nicchi Sonia , Tondi Serena , Vezzani Giacomo , Viviani Viola , Delany Isabel , Scarselli Maria , Schiavetti Francesca
Published: May 2021

Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.
The Expression Characteristics of NPF Genes and Their Response to Vernalization and Nitrogen Deficiency in Rapeseed
Authors: Chao Hongbo , He Jianjie , Cai Qianqian , Zhao Weiguo , Fu Hong , Hua Yingpeng , Li Maoteng , Huang Jinyong
Published: May 2021

The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY (NPF) genes, initially characterized as nitrate or peptide transporters in plants, are involved in the transport of a large variety of substrates, including amino acids, nitrate, auxin (IAA), jasmonates (JAs), abscisic acid (ABA) and gibberellins (GAs) and glucosinolates. A total of 169 potential functional NPF genes were excavated in Brassica napus, and they showed diversified expression patterns in 90 different organs or tissues based on transcriptome profile data. The complex time-serial expression changes were found for most functional NPF genes in the development process of leaves, silique walls and seeds, which indicated that the expression of Brassica napus NPF (BnaNPF) genes may respond to altered phytohormone and secondary metabolite content through combining with promoter element enrichment analysis. Furthermore, many BnaNPF genes were detected to respond to vernalization with two different patterns, and 20 BnaNPF genes responded to nitrate deficiency. These results will provide useful information for further investigation of the biological function of BnaNPF genes for growth and development in rapeseed.
Antioxidant Activity and Healthy Benefits of Natural Pigments in Fruits: A Review
Authors: Lu Wang , Shi Yuan , Wang Rui , Su Deding , Tang Mingfeng , Liu Yudong , Li Zhengguo
Published: May 2021

Natural pigments, including carotenoids, flavonoids and anthocyanidins, determine the attractive color of fruits. These natural pigments are essential secondary metabolites, which play multiple roles in the whole life cycle of plants and are characterized by powerful antioxidant activity. After decades of research and development, multiple benefits of these natural pigments to human health have been explored and recognized and have shown bright application prospects in food, medicine, cosmetics and other industries. In this paper, the research progress of natural fruit pigments in recent years was reviewed, including the structural characteristics and classification, distribution in fruits and analysis methods, biosynthetic process, antioxidant capacity and mechanism, bioaccessibility and bioavailability, and health benefits. Overall, this paper summarizes the recent advances in antioxidant activity and other biological functions of natural fruit pigments, which aims to provide guidance for future research.
EGCG-Mediated Potential Inhibition of Biofilm Development and Quorum Sensing in Pseudomonas aeruginosa
Authors: Hao Suqi , Yang Dan , Zhao Ling , Shi Fei , Ye Gang , Fu Hualin , Lin Juchun , Guo Hongrui , He Ran , Li Jianlong , Chen Hongwei , Khan Muhammad Faraz , Li Yinglun , Tang Huaqiao
Published: May 2021

Pseudomonas aeruginosa (P. aeruginosa), one of the dangerous multidrug resistance pathogens, orchestrates virulence factors production through quorum sensing (QS). Since the exploration of QS inhibitors, targeting virulence to circumvent bacterial pathogenesis without causing significant growth inhibition is a promising approach to treat P. aeruginosa infections. The present study has evaluated the anti-QS and anti-infective activity of epigallocatechin-3-gallate (EGCG), a bioactive ingredient of the traditional green tea, against P. aeruginosa. EGCG showed significant inhibitory effects on the development of biofilm, protease, elastase activity, swimming, and swarming motility, which was positively related to the production of C4-AHL. The expression of QS-related and QS-regulated virulence factors genes was also evaluated. Quantitative PCR analysis showed that EGCG significantly reduced the expression of las, rhl, and PQS genes and was highly correlated with the alterations of C4-AHL production. In-vivo experiments demonstrated that EGCG treatment reduced P. aeruginosa pathogenicity in Caenorhabditis elegans (C. elegans). EGCG increased the survival of C. elegans by 23.25%, 30.04%, and 36.35% in a dose-dependent manner. The findings of this study strongly suggest that EGCG could be a potential candidate for QS inhibition as an anti-virulence compound against bacterial infection.
Coexistence of Three Dominant Bacterial Symbionts in a Social Aphid and Implications for Ecological Adaptation
Authors: Liu Qian , Zhang Hui , Zeng Lingda , Yu Yuhua , Lin Xiaolan , Huang Xiaolei
Published: May 2021

Aphids are associated with an array of symbionts that have diverse ecological and evolutionary effects on their hosts. To date, symbiont communities of most aphid species are still poorly characterized, especially for the social aphids. In this study, high-throughput 16S rDNA amplicon sequencing was used to assess the bacterial communities of the social aphid Pseudoregma bambucicola, and the differences in bacterial diversity with respect to ant attendance and time series were also assessed. We found that the diversity of symbionts in P. bambucicola was low and three dominant symbionts (Buchnera, Pectobacterium and Wolbachia) were stably coexisting. Pectobacterium may help P. bambucicola feed on the hard bamboo stems, and genetic distance analysis suggests that the Pectobacterium in P. bambucicola may be a new symbiont species. Wolbachia may be associated with the transition of reproduction mode or has a nutritional role in P. bambucicola. Statistical tests on the diversity of bacterial communities in P. bambucicola suggest that aphid populations attended by ants usually have a significantly higher evenness than populations without ant attendance but there was no significant difference among aphid populations from different seasons.
Restless Leg Syndrome Is Underdiagnosed in Hereditary Hemorrhagic Telangiectasia—Results of an Online Survey
Authors: Droege Freya , Stang Andreas , Thangavelu Kruthika , Lueb Carolin , Lang Stephan , Xydakis Michael , Geisthoff Urban
Published: May 2021

Background: Recurrent bleeding in patients with hereditary hemorrhagic telangiectasia (HHT) can lead to chronic iron deficiency anemia (CIDA). Existing research points to CIDA as a contributing factor in restless leg syndrome (RLS). The association between HHT-related symptoms and the prevalence of RLS was analyzed. Methods: An online survey was conducted whereby the standardized RLS-Diagnostic Index questionnaire (RLS-DI) was supplemented with 82 additional questions relating to HHT. Results: A total of 474 persons responded to the survey and completed responses for questions pertaining to RLS (mean age: 56 years, 68% females). Per RLS-DI criteria, 48 patients (48/322, 15%; 95% confidence interval (CI): 11–19%) self-identified as having RLS. An analysis of physician-diagnosed RLS and the RLS-DI revealed a relative frequency of RLS in HHT patients of 22% (95% CI: 18–27%). In fact, 8% (25/322; 95% CI: 5–11%) of the HHT patients had RLS which had not been diagnosed before. This equals 35% of the total amount of patients diagnosed with RLS (25/72; 95% CI: 25–46%). HHT patients with a history of gastrointestinal bleeding (prevalence ratio (PR) = 2.70, 95% CI: 1.53–4.77), blood transfusions (PR = 1.90, 95% CI: 1.27–2.86), or iron intake (PR = 2.05, 95% CI: 0.99–4.26) had an increased prevalence of RLS. Conclusions: Our data suggest that RLS is underdiagnosed in HHT. In addition, physicians should assess CIDA parameters for possible iron supplementation.
Cardiovascular and Pre-Frailty Risk Assessment during Shelter-In-Place Measures Based on Multimodal Biomarkers Collected from Smart Telemedical Wearables
Authors: Kańtoch Eliasz , Kańtoch Anna
Published: May 2021

Wearable devices play a growing role in healthcare applications and disease prevention. We conducted a retrospective study to assess cardiovascular and pre-frailty risk during the Covid-19 shelter-in-place measures on human activity patterns based on multimodal biomarkers collected from smartwatch sensors. For methodology validation we enrolled five adult participants (age range: 32 to 84 years; mean 57 ± 22.38; BMI: 27.80 ± 2.95 kg/m2) categorized by age who were smartwatch users and self-isolating at home during the Covid-19 pandemic. Resting heart rate, daily steps, and minutes asleep were recorded using smartwatch sensors. Overall, we created a dataset of 464 days of continuous measurement that included 50 days of self-isolation at home during the Covid-19 pandemic. Student’s t-test was used to determine significant differences between the pre-Covid-19 and Covid-19 periods. Our findings suggest that there was a significant decrease in the number of daily steps (−57.21%; −4321; 95% CI, 3722 to 4920) and resting heart rate (−4.81%; −3.04; 95% CI, 2.59 to 3.51) during the period of self−isolation compared to the time before lockdown. We found that there was a significant decrease in the number of minutes asleep (−13.48%; −57.91; 95% CI, 16.33 to 99.49) among older adults. Finally, cardiovascular and pre-frailty risk scores were calculated based on biomarkers and evaluated from the clinical perspective.
How Much Is Enough? First Steps to a Social Ecology of the Pergamon Microregion
Authors: Laabs Julian , Knitter Daniel
Published: May 2021

In this study, we present a transparent and reproducible approach to model agricultural production with respect to environmental characteristics and available labour. Our research focuses on the city of Pergamon and its surroundings, with an emphasis on the transition between the Hellenistic and Roman Imperial Period, where widespread demographic changes took place. We investigated the degree of local self-sufficiency using different concepts of a city’s complementary region. Using simple topographic derivatives, we derive a measure of environmental suitability that we translate into a carrying capacity index. Our results show that workforce was not a limiting factor for local self-sufficiency. However, environmental carrying capacity may have been limiting in a scenario with a large population. An active investment into the environment, e.g., by the construction of terraces, could have helped to increase the degree of self-sufficiency. Future research should investigate the level of resilience of such a coupled socio-ecological system in relation to environmental and socio-cultural dynamics.
Variation in Temperature, Precipitation, and Vegetation Greenness Drive Changes in Seasonal Variation of Avian Diversity in an Urban Desert Landscape
Authors: de Albuquerque Fábio Suzart , Bateman Heather L. , Boehme Cameron , Allen Daniel C. , Cayuela Luis
Published: May 2021

Previous studies in urban desert ecosystems have reported a decline in avian diversity. Herein, we expand and improve these studies by disentangling the effect of land-use and land-cover (LULC) types (desert, riparian desert, urban, riparian urban, agriculture), vegetation greenness (normalized difference vegetation index—NDVI), climate, and their interactions on avian seasonal variation abundance and richness. Avian community data were collected seasonally (winter and spring) from 2001 to 2016. We used generalized linear mixed models (GLMM) and multimodel inference to investigate how environmental predictors explain patterns of avian richness and abundance. Avian abundance and richness oscillated considerably among the years. GLMM indicated that LULC was the most important predictor of avian abundance and richness. Avian abundance was highest in urban riparian and urban LULC types, followed by agriculture. In contrast, avian richness was the highest in riparian environments (urban and desert), followed by agriculture, urban, and desert. NDVI was also strongly related to avian abundance and richness, whereas the effect of temperature and precipitation was moderate. The importance of environmental predictors is, however, dependent on LULC. The importance of LULC, vegetation cover, and climate in influencing the seasonal patterns of avian distribution highlights birds’ sensitivity to changes in land use and cover and temperature.
Do Design Science Research and Design Thinking Processes Improve the ‘Fit’ of the Fit-For-Purpose Approach to Securing Land Tenure for All in South Africa?
Authors: Hull Simon , Whittal Jennifer
Published: May 2021

In South Africa, land tenure security is a challenge for 60% or more of the population who hold interests in land outside of the formal system of registered title. There is a need for the cadastral and land administration systems to be reshaped, and for new land tenure forms to be developed to record all land rights and interests so as to improve land tenure security for all. In this paper, we undertake a reflective retrospective of the processes of land administrative reform in South Africa using a thematic framework that includes fit-for-purpose, design science research, and design thinking processes. Literary sources are coded using the thematic framework to identify potential contributions of foregrounding design science research and design thinking in fit-for-purpose land administration (FFP LA) approaches. Design science research paired with tools of behavioral science add value in understanding the context, problems, needs, and objectives and in communicating the results of critical reflection. The design thinking process has much to offer in capitalizing on the human abilities of empathy, deep understanding, and challenging assumptions, setting the scene for unconstrained creative thinking. Design science research and design thinking within FFP LA may promote innovations in land administration systems reform initiatives that deliver restorative justice in the South African land sector.
Current Status of Brain Tumor in the Kingdom of Saudi Arabia and Application of Nanobiotechnology for Its Treatment: A Comprehensive Review
Authors: Moin Afrasim , Rizvi Syed Mohd Danish , Hussain Talib , Gowda D. V. , Subaiea Gehad M. , Elsayed Mustafa M. A. , Ansari Mukhtar , Alanazi Abulrahman Sattam , Yadav Hemant
Published: May 2021

Objective: Brain tumors are the most challenging of all tumors and accounts for about 3% of all cancer allied deaths. The aim of the present review is to examine the brain tumor prevalence and treatment modalities available in the Kingdom of Saudi Arabia. It also provides a comprehensive analysis of the application of various nanotechnology-based products for brain cancer treatments along with their prospective future advancements. Methods: A literature review was performed to identify and summarize the current status of brain cancer in Saudi Arabia and the scope of nanobiotechnology in its treatment. Results: Depending upon the study population data analysis, gliomas, astrocytoma, meningioma, and metastatic cancer have a higher incidence rate in Saudi Arabia than in other countries, and are mostly treated in accordance with conventional treatment modalities for brain cancer. Due to the poor prognosis of cancer, it has an average survival rate of 2 years. Conventional therapy includes surgery, radiotherapy, chemotherapy, and a combination thereof, but these do not control the disease’s recurrence. Among the various nanomaterials discussed, liposomes and polymeric nanoformulations have demonstrated encouraging outcomes for facilitated brain cancer treatment. Conclusions: Nanomaterials possess the capacity to overcome the shortcomings of conventional therapies. Polymer-based nanomaterials have shown encouraging outcomes against brain cancer when amalgamated with other nano-based therapies. Nonetheless, nanomaterials could be devised that possess minimal toxicity towards normal cells or that specifically target tumor cells. In addition, rigorous clinical investigations are warranted to prepare them as an efficient and safe modality for brain cancer therapy.
Many Distinct Ways Lead to Drug Resistance in BRAF- and NRAS-Mutated Melanomas
Authors: Vachtenheim Jiri , Ondrušová Lubica
Published: May 2021

Advanced melanoma is a relentless tumor with a high metastatic potential. The combat of melanoma by using the targeted therapy is impeded because several major driver mutations fuel its growth (predominantly BRAF and NRAS). Both these mutated oncogenes strongly activate the MAPK (MEK/ERK) pathway. Therefore, specific inhibitors of these oncoproteins or MAPK pathway components or their combination have been used for tumor eradication. After a good initial response, resistant cells develop almost universally and need the drug for further expansion. Multiple mechanisms, sometimes very distant from the MAPK pathway, are responsible for the development of resistance. Here, we review many of the mechanisms causing resistance and leading to the dismal final outcome of mutated BRAF and NRAS therapy. Very heterogeneous events lead to drug resistance. Due to this, each individual mechanism would be in fact needed to be determined for a personalized therapy to treat patients more efficiently and causally according to molecular findings. This procedure is practically impossible in the clinic. Other approaches are therefore needed, such as combined treatment with more drugs simultaneously from the beginning of the therapy. This could eradicate tumor cells more rapidly and greatly diminish the possibility of emerging mechanisms that allow the evolution of drug resistance.
Improvement of the Machining Performance of the TW-ECDM Process Using Magnetohydrodynamics (MHD) on Quartz Material
Authors: Oza Ankit D. , Kumar Abhishek , Badheka Vishvesh , Arora Amit , Kumar Manoj , Pruncu Catalin I. , Singh Tej
Published: May 2021

Many microslits are typically manufactured on quartz substrates and are used to improve their industrial performance. The fabrication of microslits on quartz is difficult and expensive to achieve using recent traditional machining processes due to its hardness, electrically insulating nature, and brittleness. The key objective of the current study was to demonstrate the fabrication of microslits on quartz material through a magnetohydrodynamics (MHD)-assisted traveling wire-electrochemical discharge micromachining process. Hydrogen gas bubbles were concentrated around the entire wire surface during electrolysis. This led to a less active dynamic region of the wire electrode, which decreased the adequacy of the electrolysis process and the machining effectiveness. The test results affirmed that the MHD convection approach evacuated the gas bubbles more rapidly and improved the void fraction in the gas bubble scattering layer. Furthermore, the improvements in the material removal rate and length of the cut were 85.28% and 48.86%, respectively, and the surface roughness was reduced by 30.39% using the MHD approach. A crossover methodology with a Taguchi design and ANOVA was utilized to study the machining performance. This exploratory investigation gives an unused strategy that shows a few advantages over the traditional TW-ECDM process.
Mechanical Behavior of Ultrahigh-Performance Concrete Tunnel Lining Segments
Authors: Abbas Safeer , Nehdi Moncef
Published: May 2021

Ultrahigh-performance concrete (UHPC) is a novel material demonstrating superior mechanical, durability and sustainability performance. However, its implementation in massive structures is hampered by its high initial cost and the lack of stakeholders’ confidence, especially in developing countries. Therefore, the present study explores, for the first time, a novel application of UHPC, incorporating hybrid steel fibers in precast tunnel lining segments. Reduced scale curved tunnel lining segments were cast using UHPC incorporating hybrid 8 mm and 16 mm steel fibers at dosages of 1%, 2% and 3% by mixture volume. Flexural and thrust load tests were conducted to investigate the mechanical behavior of UHPC tunnel lining segments thus produced. It was observed that the flow of UHPC mixtures decreased due to steel fibers addition, yet steel fibers increased the mechanical and durability properties. Flexural tests on lining segments showed that both the strain hardening (multiple cracking) and strain softening (post-peak behavior) phases were enhanced due to hybrid addition of steel fibers in comparison with the control segments without fibers. Specimens incorporating 3% of hybrid steel fibers achieved 57% increase in ultimate load carrying capacity and exhibited multiple cracking patterns compared to that of identical UHPC segments with 1% fibers. Moreover, segments without fibers incurred excessive cracking and spalling of concrete at the base under the thrust load test. However, more stable behavior was observed for segments incorporating steel fibers under the thrust load, indicating its capability to resist typical thrust loads during tunnel lining field installation. This study highlights the potential use of UHPC with hybrid steel fibers for improved structural behavior. Moreover, the use of UHPC allows producing structural members with reduced cross-sectional dimensions, leading to reduced overall structural weight and increased clear space.
Transformed Corrugated Shell Units Used as a Material Determining Unconventional Forms of Complex Building Structures
Authors: Abramczyk Jacek
Published: May 2021

This article is an insight into interdisciplinary topics in the field of civil engineering, morphology, architecture, mechanics, and computer programming. A novel method for shaping unconventional complex roofs in which regular folded units transformed into various shells are used as a complex substitute material is proposed. The original method’s algorithm for building systems of planes defining diversified polyhedral networks in the three-dimensional space by means of division coefficients of the subsequently determined vertices is presented. The algorithm is based on the proportions between the lengths of the edges of the reference network, the location and shape of the ruled shell units included in the designed complex roof structure, so it is intuitive. The shell units are made up of nominally flat folded sheets transformed effectively into shell forms whose static-strength properties are controlled by geometric quantities characteristic of ruled surfaces. The presented original approach to the shaping of the shell roof structures determining specific complex building forms allows us to go beyond the limitations related to the orthotropic structure of the folded roof sheeting and the shape transformations.
Investigation of Forging Metal Specimens of Different Relative Reductions Using Ultrasonic Waves
Authors: Moravec Ján , Bury Peter , Černobila František
Published: May 2021

Forgings produced in industry are an irreplaceable basis for subsequent elaborating on machine tools. The quality of the semi-finished product produced by forging is a necessary prerequisite for ensuring the final quality of the final product because the forging can produce some defects. The presented paper is aimed at investigation of selected characteristics of forging steel specimens for various levels of their relative reduction. Ultrasound testing belongs to methods for investigation of structure changes, including defects. Experimental investigation, using both the attenuation and velocity measurements, verify that the reduction of specimens’ material can have an effect on the propagation of ultrasound waves passing through the specimen body. The procedure of steel samples forging corresponds accordingly to the process of their hardening. The increase of toughness after relative reduction of forging in the range of 10–50% is with highest probability caused by the strength matrices development due to the relatively important deformation hardening. It is evident that the deformation hardening is almost the same after every 10% addition of relative reduction. Experiments are supplemented by Barkhausen noise detection and metallographic characteristics of the samples. While differences between the Barkhausen noise values are in principle relatively small and significant differences are only in the values of the position of the envelope, there is maximum coincidence with ultrasonic investigation.
A Carbon Composite Film with Three-Dimensional Reticular Structure for Electromagnetic Interference Shielding and Electro-Photo-Thermal Conversion
Authors: Lin Na , Chen Hanning , Mei Xiaokang , Chai Shitong , Lu Longsheng
Published: May 2021

The design of flexible wearable electronic devices that can shield electromagnetic waves and work in all weather conditions remains a challenge. We present in this work a low-cost technology to prepare an ultra-thin carbon fabric–graphene (CFG) composite film with outstanding electromagnetic interference shielding effectiveness (EMI SE) and electro-photo-thermal effect. The compatibility between flexible carbon fabric skeleton and brittle pure graphene matrix empowers this CFG film with adequate flexibility. The reticular fibers and porous structures play a vital role in multiple scattering and absorption of electromagnetic waves. In the frequency range of 30–1500 MHz, the CFG film can achieve a significantly high EMI SE of about 46 dB at tiny thickness (0.182 mm) and density (1.4 g cm−3) predominantly by absorption. At low safe voltages or only in sunlight, the film can self-heat to its saturation value rapidly in 40 s. Once the electricity or light supply is stopped, it can quickly dissipate heat in tens of seconds. A combination of the EMI SE and the prominent electro-photo-thermal effect further enables such a remarkable EMI shielding film to have more potential applications for communication devices in extreme zones.
Reversibility of the Magnetocaloric Effect in the Bean-Rodbell Model
Authors: Moreno-Ramírez Luis M. , Franco Victorino
Published: May 2021

The applicability of magnetocaloric materials is limited by irreversibility. In this work, we evaluate the reversible magnetocaloric response associated with magnetoelastic transitions in the framework of the Bean-Rodbell model. This model allows the description of both second- and first-order magnetoelastic transitions by the modification of the η parameter (η<1 for second-order and η>1 for first-order ones). The response is quantified via the Temperature-averaged Entropy Change (TEC), which has been shown to be an easy and effective figure of merit for magnetocaloric materials. A strong magnetic field dependence of TEC is found for first-order transitions, having a significant increase when the magnetic field is large enough to overcome the thermal hysteresis of the material observed at zero field. This field value, as well as the magnetic field evolution of the transition temperature, strongly depend on the atomic magnetic moment of the material. For a moderate magnetic field change of 2 T, first-order transitions with η≈1.3−1.8 have better TEC than those corresponding to stronger first-order transitions and even second-order ones.
Magnetic and Structural Properties of Organic Radicals Based on Thienyl- and Furyl-Substituted Nitronyl Nitroxide
Authors: Sugano Tadashi , Blundell Stephen J. , Hayes William , Mori Hatsumi
Published: May 2021

Magnetic properties of organic radicals based on thienyl- and furyl-substituted nitronyl nitroxide (NN) and iminonitroxide (IN) were investigated by measuring the temperature dependence of the magnetization. The magnetic behavior of 2-benzo[b]thienyl NN (2-BTHNN) is interpreted in terms of the two-magnetic-dimer model, in which one dimer exhibits ferromagnetic (FM) intermolecular interaction and the other dimer shows antiferromagnetic (AFM) interaction. The existence of two dimers in 2-BTHNN is supported by crystal structure analysis. The magnetic behaviors of 2-bithienyl NN, 4-(2′-thienyl)phenyl NN (2-THPNN), 2- and 3-furyl NN, 2-benzo[b]furyl NN, and 3-benzo[b]thienyl IN are also reported. The one-dimensional alternating AFM nature observed in 2-THPNN is consistent with its crystal structure.
Packaging Process Optimization in Multihead Weighers with Double-Layered Upright and Diagonal Systems
Authors: García-Jiménez Rafael , García-Díaz J. Carlos , Pulido-Rojano Alexander D.
Published: May 2021

In multihead weighers, packaging processes seek to find the best combination of passage hoppers whose product content provides a total package weight as close as possible to its (nominal) label weight. The weighing hoppers arranged in these machines dispense the product quantity that each package contains through computer algorithms designed and executed for this purpose. For its part, in the packaging process for double-layered multihead weighers, all hoppers are arranged in two levels. The first layer comprises a group of weighing hoppers, and the second comprises a set of booster hoppers placed uprightly or diagonally to each weighing hopper based on design of the machine. In both processes, the initial machine configuration is the same; however, the hopper selection algorithm works differently. This paper proposes a new packaging process optimization algorithm for double-layer upright and diagonal machines, wherein the hopper subset combined has previously been defined, and the packaging weight is expressed as actual values. As part of its validation, product filling strategies were implemented for weighing hoppers to assess the algorithm in different scenarios. Results from the process performance metrics prove that the new algorithm improves processes by reducing variability. In addition, results reveal that some machine configurations were also able to improve their operation.
Alternative Financial Methods for Improving the Investment in Renewable Energy Companies
Authors: Miralles-Quirós José Luis , Miralles-Quirós María Mar
Published: May 2021

Renewable energies have increased in importance in recent years due to the harm caused to the environment by fossil fuels. As a result, renewable energy companies seem to be profitable investment opportunities given their likely substantial future earnings. However, previous empirical evidence has not always agreed about this likely profitability. In addition, the methodologies employed in the existing empirical literature are complicated and not feasible for most investors to use. Therefore, it is proposed an approach which combines the use of performance measures, screening rules, devolatized returns and portfolio strategies, all of which can be implemented by investors. This approach results in high cumulative returns of more than 200% and other positive ratios, even when transaction costs are considered. This should encourage people to invest in these renewable energies and contribute to improving the environment.
Optimal Design of High-Voltage Disconnecting Switch Drive System Based on ADAMS and Particle Swarm Optimization Algorithm
Authors: Liu Benxue , Yuan Peng , Wang Mengjian , Bi Cheng , Liu Chong , Li Xia
Published: May 2021

This paper focuses on the analysis of the stability of the GW17 high-voltage disconnecting switch drive system. Firstly, the optimization model of the disconnector is established, and the simulation analysis is carried out by ADAMS (Automatic Dynamic Analysis of Mechanical Systems) and the simulation results are verified by experiments. Afterwards, ADAMS optimization design and particle swarm optimization algorithm (PSO) are used to optimize the drive system of the disconnector, and the results are verified on the experimental platform. After optimization, the space rod is reduced by 15 mm, the minimum corner angle of the lower conductive rod is reduced by 71.0%, the minimum folding arm angle is reduced by 88.7% and the maximum force of the ball pair is reduced by 35.7%, which realizes the lightweight of the rod, reduces the wear of the ball pair, and improves the stability of the equipment operation.
Study of the Residual Bond Strength between Corroded Steel Bars and Concrete—A Comparison with the Recommendations of Fib Model Code 2010
Authors: Koulouris Konstantinos , Apostolopoulos Charis
Published: May 2021

As is well known, corrosion of steel reinforcement deteriorates the steel–concrete interface and causes concrete cracking, degrading significantly the bond strength. Several experimental studies have investigated the magnitude of residual bond strength due to corrosion, which affects either the function of corrosion-damaged steel bars or the surface crack width in concrete. As a result, linear and exponential correlation relationships have been proposed in order to predict the bond loss due to corrosion. Based on the results of an ongoing experimental campaign on the degradation of bond strength of RC specimens, combined with comparable outcomes from existing literature, this manuscript summarizes a database, comparing with the recommendations of Model Code 2010, to analyze and interpret the corrosion effect on the bond loss and highlights some points that need improvement in the current regulations. As indicated, the density of transverse reinforcement (stirrups spacing) has intense impact on the resulting bond loss due to corrosion. Hence, in order to quantify this aspect, the present manuscript introduces a discretization of confinement levels of RC elements, depending on the stirrups spacing. Based on this, regression analyses of data were conducted to extract fitting curves of bond loss, taking into account the amount of transverse reinforcement and predictive zones of residual bond strength in relationship to either corrosion penetration or surface crack width. Furthermore, the outcomes demonstrate that the corrosion penetration depth is an appropriate assessment tool to correlate the residual bond strength with the corrosion level, whereas the surface crack width on concrete is not yet an effective index, since there is a plethora of factors affecting the crack width. Due to this, more research is needed to improve the current level of knowledge on the surface crack width and link it with the corrosion damage of the steel bar and the residual bond strength due to corrosion.