bluuebunny/crossref_metadata_2025 huggingface dataset:
Whether Green Finance Can Effectively Moderate the Green Technology Innovation Effect of Heterogeneous Environmental Regulation
Authors: Fang Yong , Shao Zhenquan
Published: March 2022

As an essential way to promote ecological civilization, green finance is attracting wide attention. However, whether green finance can successfully regulate the green technology innovation effect of heterogeneous environmental regulations and boost green technology innovation in coordination with heterogeneous environmental regulations remains unclear. Based on the re-measurement of the green finance development index of various provinces and cities in China, this study uses the spatial Durbin model to test the above problems empirically. The results show that green finance and “market incentive” environmental regulations can promote regional green technology innovation, while “command and control” environmental regulations inhibit regional green technology innovation. Green finance plays a negative regulatory role in the mechanism of heterogeneous environmental regulations affecting green technology innovation. Green finance alleviates the negative impact of “command and control” environmental regulations on green technology innovation and weakens the positive impact of “market-incentive” environmental regulations on green technology innovation. In terms of spillover effects, green finance can effectively promote green technology innovation in neighboring regions, while heterogeneous environmental regulations have a crowding-out effect on green technology innovation in neighboring regions.
Variables Influencing Professors’ Adaptation to Digital Learning Environments during the COVID-19 Pandemic
Authors: Vergara-Rodríguez Diego , Antón-Sancho Álvaro , Fernández-Arias Pablo
Published: March 2022

This paper conducts quantitative research on the influence of the COVID-19 pandemic on the adaptation to digital learning environments (DLE) of a group of 908 university professors. We compared the perceptions of participants who were digital natives (born before 1980) with those of digital immigrants (born after 1980). For this purpose, a validated survey was used and the obtained responses statistically analyzed. The results show a negative correlation between pandemic stress and the digital competence of professors and their adaptation skills to digital environments, which although weak for both of the two groups compared are stronger for digital immigrants. Both self-confidence and digital competence show a positive influence on the perception of adaptation of skills to DLE, and this is weaker in digital natives. Gaps were identified by gender and area of knowledge of the participants; consequently, the need to carry out training actions for university faculty on skills linked to their digital competence in teaching is clear.
Exposure and Risk Assessment of Second- and Third-Hand Tobacco Smoke Using Urinary Cotinine Levels in South Korea
Authors: Yang Jiyeon , Hashemi Shervin , Han Wonseok , Song Yoojin , Lim Youngwook
Published: March 2022

Exposure to environmental tobacco smoke (ETS) is the reason for approximately 1% of global mortality. ETS exposure can happen either as inhalation of direct cigarette smoke (second-hand smoke) or its associated residue particles (third-hand smoke), especially when living with a smoker in the same family. This study investigated the association between the urinary cotinine levels, as biomarkers of exposure to tobacco smoke, of smokers and those exposed to second-hand and third-hand smoke while living in the same family, through a Korean nationwide survey. Direct assessment of ETS exposure and its lifetime effect on human health is practically difficult. Therefore, this study evaluated the internal estimated daily intake (I-EDI) of nicotine and equivalent smoked cigarette per day (CPD). The carcinogenic and non-carcinogenic inhalation risks of ETS exposure were assessed by considering the calculated equivalent CPD and composition of cigarette smoke of high-selling cigarette brands in South Korea. The results show that there is a statistically significant positive correlation between the cotinine levels of smokers and those of the non-smokers living in the same family. The risk assessment results yielded that hazard index (HI) and total excess lifetime cancer risk (ECR) for both second-hand and third-hand smoke exposure can exceed 1 and 1 × 10−6, respectively, especially in women and children. In the composition of the cigarette smoke, 1,3-butadiene and acrolein substances had the highest contribution to HI and ECR. Consequently, the provision of appropriate plans for smoking cessation as a strategy for the prevention of ETS exposure to women and children is deemed necessary.
Financial Regulation, Financial Inclusion and Competitiveness in the Banking Sector in SADC and SAARC Countries: The Moderating Role of Financial Stability
Authors: Jungo João , Madaleno Mara , Botelho Anabela
Published: March 2022

Financial inclusion is a widely used measure to improve the living standards of households and foster inclusive economic growth. Thus, financial inclusion is one of the main policy objectives in developing countries. Besides, financial regulation (capital adequacy requirement) is a policy measure used to ensure financial stability. The objective of this study is to examine the effect of financial regulation on competitiveness and financial inclusion in 15 countries in the SADC (Southern Africa Development Community) region and 8 countries in the SAARC (South Asian Association for Regional Cooperation) region over the period 2005–2018. The result of Feasible Generalized Least Squares (FGLS) estimation suggests that financial regulation reduces competitiveness and hampers financial inclusion in the banking sector in the two regions. Furthermore, we find that financial stability moderates the negative effect of financial regulation on competitiveness and financial inclusion, meaning that financially stable banks remain competitive and normally offer financial products and services even if strong capital adequacy requirements are implemented. Additionally, we find that competitiveness increases financial inclusion in countries in the SADC region. The policy implication of this study focuses on regulatory flexibility to preserve the need for greater financial inclusion in the two regions. As for the practical implication, the study calls for strategic measures to preserve stability such as complementing financial inclusion with financial literacy, fostering corporate governance.
A Fine-Grain Batching-Based Task Allocation Algorithm for Spatial Crowdsourcing
Authors: Jiao Yuxin , Lin Zhikun , Yu Long , Wu Xiaozhu
Published: March 2022

Task allocation is a critical issue of spatial crowdsourcing. Although the batching strategy performs better than the real-time matching mode, it still has the following two drawbacks: (1) Because the granularity of the batch size set obtained by batching is too coarse, it will result in poor matching accuracy. However, roughly designing the batch size for all possible delays will result in a large computational overhead. (2) Ignoring non-stationary factors will lead to a change in optimal batch size that cannot be found as soon as possible. Therefore, this paper proposes a fine-grained, batching-based task allocation algorithm (FGBTA), considering non-stationary setting. In the batch method, the algorithm first uses variable step size to allow for fine-grained exploration within the predicted value given by the multi-armed bandit (MAB) algorithm and uses the results of pseudo-matching to calculate the batch utility. Then, the batch size with higher utility is selected, and the exact maximum weight matching algorithm is used to obtain the allocation result within the batch. In order to cope with the non-stationary changes, we use the sliding window (SW) method to retain the latest batch utility and discard the historical information that is too far away, so as to finally achieve refined batching and adapt to temporal changes. In addition, we also take into account the benefits of requesters, workers, and the platform. Experiments on real data and synthetic data show that this method can accomplish the task assignment of spatial crowdsourcing effectively and can adapt to the non-stationary setting as soon as possible. This paper mainly focuses on the spatial crowdsourcing task of ride-hailing.
Temperature Accuracy Analysis by Land Cover According to the Angle of the Thermal Infrared Imaging Camera for Unmanned Aerial Vehicles
Authors: Lee Kirim , Lee Won Hee
Published: March 2022

Land surface temperature (LST) is one of the crucial factors that is important in various fields, including the study of climate change and the urban heat island (UHI) phenomenon. The existing LST was acquired using satellite imagery, but with the development of unmanned aerial vehicles (UAV) and thermal infrared (TIR) cameras, it has become possible to acquire LST with a spatial resolution of cm. The accuracy evaluation of the existing TIR camera for UAV was conducted by shooting vertically. However, in the case of a TIR camera, the temperature value may change because the emissivity varies depending on the viewing angle. Therefore, it is necessary to evaluate the accuracy of the TIR camera according to each angle. In this study, images were simultaneously acquired at 2–min intervals for each of the three research sites by TIR camera angles (70°, 80°, 90°). Then, the temperature difference by land cover was evaluated with respect to the LST obtained by laser thermometer and the LST obtained using UAV and TIR. As a result, the image taken at 80° showed the smallest difference compared with the value obtained with a laser thermometer, and the 70° image showed a large difference of 1–6 °C. In addition, in the case of the impervious surface, there was a large temperature difference by angle, and in the case of the water-permeable surface, there was no temperature difference by angle. Through this, 80° is best when acquiring TIR data, and if it is impossible to take images at 80°, it is considered good to acquire TIR images between 80° and 90°. To obtain more accurate LST, correction studies considering the external environment, camera attitude, and shooting height are needed in future studies.
A Geospatial Platform for Crowdsourcing Green Space Area Management Using GIS and Deep Learning Classification
Authors: Puttinaovarat Supattra , Horkaew Paramate
Published: March 2022

Green space areas are one of the key factors in people’s livelihoods. Their number and size have a significant impact on both the environment and people’s quality of life, including their health. Accordingly, government agencies often rely on information relating to green space areas when devising suitable plans and mandating necessary regulations. At present, obtaining information on green space areas using conventional ground surveys faces a number of limitations. This approach not only requires a lengthy period, but also tremendous human and financial resources. Given such restrictions, the status of a green space is not always up to date. Although software applications, especially those based on geographical information systems and remote sensing, have increasingly been applied to these tasks, the capability to use crowdsourcing data and produce real-time reports is lacking. This is partly because the quantity of data required has, to date, prohibited effective verification by human operators. To address this issue, this paper proposes a novel geospatial platform for green space area management by means of GIS and artificial intelligence. In the proposed system, all user-submitted data are automatically verified by deep learning classification and analyses of the greenness areas on satellite imagery. The experimental results showed that the classification and analyses can identify green space areas at accuracies of 93.50% and 97.50%, respectively. To elucidate the merits of the proposed approach, web-based application software was implemented to demonstrate multimodal data management, cleansing, and reporting. This geospatial system was thus proven to be a viable tool for assisting governmental agencies to devise appropriate plans toward sustainable development goals.
An Urban Hot/Cold Spot Detection Method Based on the Page Rank Value of Spatial Interaction Networks Constructed from Human Communication Records
Authors: Zhang Haitao , Shen Huixian , Ji Kang , Song Rui , Liu Jinyuan , Yang Yuxin
Published: March 2022

Applying spatial clustering algorithms on large-scale spatial interactive dataset to find urban hot/cold spots is a new idea to assist urban management. However, the research usually focuses on the dataset with spatio-temporal proximity, rather than remote dataset. This article proposes a spatial hot/cold spot detection method for human communication by auto-correlating the PageRank values of the spatial interaction networks constructed by records. Milan was selected as the study area, and the spatial interaction records reflected by telephone calls, the land-use dataset, and the POI dataset were used as experimental data. The results showed that the proposed method can be applied to long-distance spatial interactive recording data, and the hot/cold spot were clearly distinguished by the statistical distribution of the containing land-use dataset and the POI dataset. These differences were consistent with the actual situation in the study area, indicating the accuracy of the proposed method for detecting hot/cold areas.
Oncogenic Pathways in Neurodegenerative Diseases
Authors: Varela Luis , Garcia-Rendueles Maria E. R.
Published: March 2022

Cancer and neurodegenerative diseases are two of the leading causes of premature death in modern societies. Their incidence continues to increase, and in the near future, it is believed that cancer will kill more than 20 million people per year, and neurodegenerative diseases, due to the aging of the world population, will double their prevalence. The onset and the progression of both diseases are defined by dysregulation of the same molecular signaling pathways. However, whereas in cancer, these alterations lead to cell survival and proliferation, neurodegenerative diseases trigger cell death and apoptosis. The study of the mechanisms underlying these opposite final responses to the same molecular trigger is key to providing a better understanding of the diseases and finding more accurate treatments. Here, we review the ten most common signaling pathways altered in cancer and analyze them in the context of different neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) diseases.
Assessment of Automated Flow Cytometry Data Analysis Tools within Cell and Gene Therapy Manufacturing
Authors: Cheung Melissa , Campbell Jonathan J. , Thomas Robert J. , Braybrook Julian , Petzing Jon
Published: March 2022

Flow cytometry is widely used within the manufacturing of cell and gene therapies to measure and characterise cells. Conventional manual data analysis relies heavily on operator judgement, presenting a major source of variation that can adversely impact the quality and predictive potential of therapies given to patients. Computational tools have the capacity to minimise operator variation and bias in flow cytometry data analysis; however, in many cases, confidence in these technologies has yet to be fully established mirrored by aspects of regulatory concern. Here, we employed synthetic flow cytometry datasets containing controlled population characteristics of separation, and normal/skew distributions to investigate the accuracy and reproducibility of six cell population identification tools, each of which implement different unsupervised clustering algorithms: Flock2, flowMeans, FlowSOM, PhenoGraph, SPADE3 and SWIFT (density-based, k-means, self-organising map, k-nearest neighbour, deterministic k-means, and model-based clustering, respectively). We found that outputs from software analysing the same reference synthetic dataset vary considerably and accuracy deteriorates as the cluster separation index falls below zero. Consequently, as clusters begin to merge, the flowMeans and Flock2 software platforms struggle to identify target clusters more than other platforms. Moreover, the presence of skewed cell populations resulted in poor performance from SWIFT, though FlowSOM, PhenoGraph and SPADE3 were relatively unaffected in comparison. These findings illustrate how novel flow cytometry synthetic datasets can be utilised to validate a range of automated cell identification methods, leading to enhanced confidence in the data quality of automated cell characterisations and enumerations.
Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence
Authors: Koliaki Chrysi , Katsilambros Nicholas
Published: March 2022

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease.
Phosphatidic Acid in Plant Hormonal Signaling: From Target Proteins to Membrane Conformations
Authors: Kolesnikov Yaroslav , Kretynin Serhii , Bukhonska Yaroslava , Pokotylo Igor , Ruelland Eric , Martinec Jan , Kravets Volodymyr
Published: March 2022

Cells sense a variety of extracellular signals balancing their metabolism and physiology according to changing growth conditions. Plasma membranes are the outermost informational barriers that render cells sensitive to regulatory inputs. Membranes are composed of different types of lipids that play not only structural but also informational roles. Hormones and other regulators are sensed by specific receptors leading to the activation of lipid metabolizing enzymes. These enzymes generate lipid second messengers. Among them, phosphatidic acid (PA) is a well-known intracellular messenger that regulates various cellular processes. This lipid affects the functional properties of cell membranes and binds to specific target proteins leading to either genomic (affecting transcriptome) or non-genomic responses. The subsequent biochemical, cellular and physiological reactions regulate plant growth, development and stress tolerance. In the present review, we focus on primary (genome-independent) signaling events triggered by rapid PA accumulation in plant cells and describe the functional role of PA in mediating response to hormones and hormone-like regulators. The contributions of individual lipid signaling enzymes to the formation of PA by specific stimuli are also discussed. We provide an overview of the current state of knowledge and future perspectives needed to decipher the mode of action of PA in the regulation of cell functions.
SARS-CoV-2 Associated Immune Dysregulation and COVID-Associated Pulmonary Aspergilliosis (CAPA): A Cautionary Tale
Authors: Worku Dominic Adam
Published: March 2022

As the global SARS-CoV-2 pandemic continues to plague healthcare systems, it has become clear that opportunistic pathogens cause a considerable proportion of SARS-CoV-2-associated mortality and morbidity cases. Of these, Covid-Associated Pulmonary Aspergilliosis (CAPA) is a major concern with evidence that it occurs in the absence of traditional risk factors such as neutropenia and is diagnostically challenging for the attending physician. In this review, we focus on the immunopathology of SARS-CoV-2 and how this potentiates CAPA through dysregulation of local and systemic immunity as well as the unintended consequences of approved COVID treatments including corticosteroids and IL-6 inhibitors. Finally, we will consider how knowledge of the above may aid in the diagnosis of CAPA using current diagnostics and what treatment should be instituted in probable and confirmed cases.
Compendium on Food Crop Plants as a Platform for Pharmaceutical Protein Production
Authors: Gerszberg Aneta , Hnatuszko-Konka Katarzyna
Published: March 2022

Tremendous advances in crop biotechnology related to the availability of molecular tools and methods developed for transformation and regeneration of specific plant species have been observed. As a consequence, the interest in plant molecular farming aimed at producing the desired therapeutic proteins has significantly increased. Since the middle of the 1980s, recombinant pharmaceuticals have transformed the treatment of many serious diseases and nowadays are used in all branches of medicine. The available systems of the synthesis include wild-type or modified mammalian cells, plants or plant cell cultures, insects, yeast, fungi, or bacteria. Undeniable benefits such as well-characterised breeding conditions, safety, and relatively low costs of production make plants an attractive yet competitive platform for biopharmaceutical production. Some of the vegetable plants that have edible tubers, fruits, leaves, or seeds may be desirable as inexpensive bioreactors because these organs can provide edible vaccines and thus omit the purification step of the final product. Some crucial facts in the development of plant-made pharmaceuticals are presented here in brief. Although crop systems do not require more strictly dedicated optimization of methodologies at any stages of the of biopharmaceutical production process, here we recall the complete framework of such a project, along with theoretical background. Thus, a brief review of the advantages and disadvantages of different systems, the principles for the selection of cis elements for the expression cassettes, and available methods of plant transformation, through to the protein recovery and purification stage, are all presented here. We also outline the achievements in the production of biopharmaceuticals in economically important crop plants and provide examples of their clinical trials and commercialization.
Full-Length Transcriptome and RNA-Seq Analyses Reveal the Mechanisms Underlying Waterlogging Tolerance in Kiwifruit (Actinidia valvata)
Authors: Li Zhi , Bai Danfeng , Zhong Yunpeng , Lin Miaomiao , Sun Leiming , Qi Xiujuan , Hu Chungen , Fang Jinbao
Published: March 2022

Actinidia valvata possesses waterlogging tolerance; however, the mechanisms underlying this trait are poorly characterized. Here, we performed a transcriptome analysis by combining single-molecule real-time (SMRT) sequencing and Illumina RNA sequencing and investigated the physiological responses of the roots of KR5 (A. valvata, a tolerant genotype) after 0, 12, 24 and 72 h of waterlogging stress. KR5 roots responded to waterlogging stress mainly via carbohydrate and free amino acids metabolism and reactive oxygen species (ROS) scavenging pathways. Trehalose-6-phosphate synthase (TPS) activity, alcohol dehydrogenase (ADH) activity and the total free amino acid content increased significantly under waterlogging stress. The nicotinamide adenine dinucleotide-dependent glutamate synthase/alanine aminotransferase (NADH-GOGAT/AlaAT) cycle was correlated with alanine accumulation. Levels of genes encoding peroxidase (POD) and catalase (CAT) decreased and enzyme activity increased under waterlogging stress. Members of the LATERAL ORGAN BOUNDARIES (LOB), AP2/ERF-ERF, Trihelix and C3H transcription factor families were identified as potential regulators of the transcriptional response. Several hub genes were identified as key factors in the response to waterlogging stress by a weighted gene co-expression network analysis (WGCNA). Our results provide insights into the factors contributing to waterlogging tolerance in kiwifruit, providing a basis for further studies of interspecific differences in an important plant trait and for molecular breeding.
MicroRNA Cross-Involvement in Acne Vulgaris and Hidradenitis Suppurativa: A Literature Review
Authors: Borgia Francesco , Peterle Lucia , Custurone Paolo , Vaccaro Mario , Pioggia Giovanni , Gangemi Sebastiano
Published: March 2022

Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.
Vector and Host C-Type Lectin Receptor (CLR)–Fc Fusion Proteins as a Cross-Species Comparative Approach to Screen for CLR–Rift Valley Fever Virus Interactions
Authors: Schön Kathleen , Lindenwald Dimitri L. , Monteiro João T. , Glanz Julien , Jung Klaus , Becker Stefanie C. , Lepenies Bernd
Published: March 2022

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to Africa and the Arabian Peninsula, which causes diseases in humans and livestock. C-type lectin receptors (CLRs) represent a superfamily of pattern recognition receptors that were reported to interact with diverse viruses and contribute to antiviral immune responses but may also act as attachment factors or entry receptors in diverse species. Human DC-SIGN and L-SIGN are known to interact with RVFV and to facilitate viral host cell entry, but the roles of further host and vector CLRs are still unknown. In this study, we present a CLR–Fc fusion protein library to screen RVFV–CLR interaction in a cross-species approach and identified novel murine, ovine, and Aedes aegypti RVFV candidate receptors. Furthermore, cross-species CLR binding studies enabled observations of the differences and similarities in binding preferences of RVFV between mammalian CLR homologues, as well as more distant vector/host CLRs.
Physical Exercise, a Potential Non-Pharmacological Intervention for Attenuating Neuroinflammation and Cognitive Decline in Alzheimer’s Disease Patients
Authors: Ribarič Samo
Published: March 2022

This narrative review summarises the evidence for considering physical exercise (PE) as a non-pharmacological intervention for delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Ageing is the most important risk factor for AD. A hallmark of the ageing process is a systemic low-grade chronic inflammation that also contributes to neuroinflammation. Neuroinflammation is associated with AD, Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders. Pharmacological treatment of AD is currently limited to mitigating the symptoms and attenuating progression of the disease. AD animal model studies and human studies on patients with a clinical diagnosis of different stages of AD have concluded that PE attenuates cognitive decline not only by improving cardiovascular fitness but possibly also by attenuating neuroinflammation. Therefore, low-grade chronic inflammation and neuroinflammation should be considered potential modifiable risk factors for AD that can be attenuated by PE. This opens the possibility for personalised attenuation of neuroinflammation that could also have important health benefits for patients with other inflammation associated brain disorders (i.e., Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders). In summary, life-long, regular, structured PE should be considered as a supplemental intervention for attenuating the progression of AD in human. Further studies in human are necessary to develop optimal, personalised protocols, adapted to the progression of AD and the individual’s mental and physical limitations, to take full advantage of the beneficial effects of PE that include improved cardiovascular fitness, attenuated systemic inflammation and neuroinflammation, stimulated brain Aβ peptides brain catabolism and brain clearance.
Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin
Authors: Kawaguchi Kotoku , Asano Shinji
Published: March 2022

Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure about forty years ago. Since then, it has been revealed as a key protein with functions in a variety of fields including cell migration, survival, and signal transduction, as well as functioning as a structural component. Ezrin acts as a cross-linker of membrane proteins or phospholipids in the plasma membrane and the actin cytoskeleton. It also functions as a platform for signaling molecules at the cell surface. Moreover, ezrin is regarded as an important target protein in cancer diagnosis and therapy because it is a key protein involved in cancer progression and metastasis, and its high expression is linked to poor survival in many cancers. Small molecule inhibitors of ezrin have been developed and investigated as candidate molecules that suppress cancer metastasis. Here, we wish to comprehensively review the roles of ezrin from the pathophysiological points of view.
The EPH/Ephrin System in Gynecological Cancers: Focusing on the Roots of Carcinogenesis for Better Patient Management
Authors: Psilopatis Iason , Pergaris Alexandros , Vrettou Kleio , Tsourouflis Gerasimos , Theocharis Stamatios
Published: March 2022

Gynecological cancers represent some of the most common types of malignancy worldwide. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest subfamily of receptor tyrosine kinases, binding membrane-bound proteins called ephrins. EPHs/ephrins exhibit widespread expression in different cell types, playing an important role in carcinogenesis. The aim of the current review was to examine the dysregulation of the EPH/ephrin system in gynecological cancer, clarifying its role in ovarian, endometrial, and cervical carcinogenesis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms ephrin, ephrin receptor, ovarian cancer, endometrial cancer, and cervical cancer were employed and we were able to identify 57 studies focused on gynecological cancer and published between 2001 and 2021. All researched ephrins seemed to be upregulated in gynecological cancer, whereas EPHs showed either significant overexpression or extensive loss of expression in gynecological tumors, depending on the particular receptor. EPHA2, the most extensively studied EPH in ovarian cancer, exhibited overexpression both in ovarian carcinoma cell lines and patient tissue samples, while EPHB4 was found to be upregulated in endometrial cancer in a series of studies. EPHs/ephrins were shown to exert their role in different stages of gynecological cancer and to influence various clinicopathological parameters. The analysis of patients’ gynecological cancer tissue samples, most importantly, revealed the significant role of the EPH/ephrin system in the development and progression of gynecological cancer, as well as overall patient survival. In conclusion, the EPH/ephrin system represents a large family of biomolecules with promising applications in the fields of diagnosis, prognosis, disease monitoring, and treatment of gynecological cancer, with an established important clinical impact.
The Inflammatory Conspiracy in Multiple Sclerosis: A Crossroads of Clues and Insights through Mast Cells, Platelets, Inflammation, Gut Microbiota, Mood Disorders and Stem Cells
Authors: Cocchi Massimo , Mondo Elisabetta , Romeo Marcello , Traina Giovanna
Published: March 2022

Multiple Sclerosis is a chronic neurological disease characterized by demyelination and axonal loss. This pathology, still largely of unknown etiology, carries within it a complex series of etiopathogenetic components of which it is difficult to trace the origin. An inflammatory state is likely to be the basis of the pathology. Crucial elements of the inflammatory process are the interactions between platelets and mast cells as well as the bacterial component of the intestinal microbiota. In addition, the involvement of mast cells in autoimmune demyelinating diseases has been shown. The present work tries to hang up on that Ariadne’s thread which, in the molecular complexity of the interactions between mast cells, platelets, microbiota and inflammation, characterizes Multiple Sclerosis and attempts to bring the pathology back to the causal determinism of psychopathological phenomenology. Therefore, we consider the possibility that the original error of Multiple Sclerosis can be investigated in the genetic origin of the depressive pathology.
A Histone Deacetylase (HDAC) Inhibitor with Pleiotropic In Vitro Anti-Toxoplasma and Anti-Plasmodium Activities Controls Acute and Chronic Toxoplasma Infection in Mice
Authors: Jublot Delphine , Cavaillès Pierre , Kamche Salima , Francisco Denise , Fontinha Diana , Prudêncio Miguel , Guichou Jean-Francois , Labesse Gilles , Sereno Denis , Loeuillet Corinne
Published: March 2022

Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of Toxoplasma strains, as well as against the liver and blood stages of Plasmodium parasites, the causative agents of malaria. In vivo administration of the drug significantly increases the survival of mice during the acute phase of infection by T. gondii, thus delaying its spreading. We further provide evidence of the compound’s efficiency in controlling the formation of cysts in the brain of T. gondii-infected mice. A convincing docking of the JF363 compound in the active site of the five annotated ME49 T. gondii HDACs was performed by extensive sequence–structure comparison modeling. The resulting complexes show a similar mode of binding in the five paralogous structures and a quite similar prediction of affinities in the micromolar range. Altogether, these results pave the way for further development of this compound to treat acute and chronic toxoplasmosis. It also shows promise for the future development of anti-Plasmodium therapeutic interventions.
In Vitro Studies Regarding the Safety of Chitosan and Hyaluronic Acid-Based Nanohydrogels Containing Contrast Agents for Magnetic Resonance Imaging
Authors: Gheran Cecilia Virginia , Voicu Sorina Nicoleta , Galateanu Bianca , Callewaert Maité , Moreau Juliette , Cadiou Cyril , Chuburu Françoise , Dinischiotu Anca
Published: March 2022

The aim of this study was to investigate the biocompatibility of contrast agents, such as gadolinium 1, 4, 7, 10 tetraazacyclo-dodecane tetraacetic acid (GdDOTA) and gadolinium dioctyl terephthalate (GdDOTP), encapsulated in a polymeric matrix containing chitosan and hyaluronic acid using RAW264.7 murine macrophages and human blood samples. The cell viability and cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, while cell cycle analysis was determined in RAW264.7 cells using flow cytometry. The mitochondrial membrane potential (MMP), hemolytic index, complement activation, and thrombogenic potential of gadolinium (Gd) containing nanohydrogels were measured by fluorometric and spectrophotometric methods. Taken together, our results demonstrate the good bio- and hemocompatibility of chitosan-based nanohydrogels with the RAW264.7 cell line and human blood cells, suggesting that these could be used as injectable formulations for the magnetic resonance imaging diagnostic of lymph nodes.
Polymeric Hydrogels for In Vitro 3D Ovarian Cancer Modeling
Authors: Braccini Simona , Tacchini Chiara , Chiellini Federica , Puppi Dario
Published: March 2022

Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture.
Sex Hormones and Their Effects on Ocular Disorders and Pathophysiology: Current Aspects and Our Experience
Authors: Nuzzi Raffaele , Caselgrandi Paolo
Published: March 2022

Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies.
Hydrogels in Regenerative Medicine and Other Biomedical Applications
Authors: Jervis Peter J.
Published: March 2022

It is my great pleasure to be part of this Special Issue in the International Journal of Molecular Sciences—“Hydrogels in Regenerative Medicine and Other Biomedical Applications” [...]
Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis
Authors: Oliva-Rico Diego , Fabian-Morales Eunice , Cáceres-Gutiérrez Rodrigo E. , Gudiño Adriana , Cisneros-Soberanis Fernanda , Dominguez Julieta , Almaraz-Rojas Oscar , Arriaga-Canon Cristian , Castro-Hernández Clementina , De la Rosa Carlos , Reyes José L. , Herrera Luis A.
Published: March 2022

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.
Transcriptomic Identification of Wheat AP2/ERF Transcription Factors and Functional Characterization of TaERF-6-3A in Response to Drought and Salinity Stresses
Authors: Yu Yang , Yu Ming , Zhang Shuangxing , Song Tianqi , Zhang Mingfei , Zhou Hongwei , Wang Yukun , Xiang Jishan , Zhang Xiaoke
Published: March 2022

AP2/ERF (APETALA2/ethylene responsive factor) is a family of plant-specific transcription factors whose members are widely involved in many biological processes, such as growth, development, and biotic and abiotic stress responses. Here, 20 AP2/ERF genes were identified based on wheat RNA-seq data before and after drought stress, and classified as AP2, ERF, DREB, and RAV. The analysis of gene structure revealed that about 85% of AP2/ERF family members had lost introns, which are presumed to have been lost during the formation and evolution of the wheat genome. The expression of 20 AP2/ERF family genes could be verified by qRT-PCR, which further supported the validity of the RNA-seq data. Subsequently, subcellular localization and transcriptional activity experiments showed that the ERF proteins were mainly located in the nucleus and were self-activating, which further supports their functions as transcription factors. Furthermore, we isolated a novel ERF gene induced by drought, salt, and cold stresses and named it TaERF-6-3A. TaERF-6-3A overexpression increased sensitivity to drought and salt stresses in Arabidopsis, which was supported by physiological and biochemical indices. Moreover, the expression of stress- and antioxidant-related genes was downregulated in TaERF-6-3A-overexpressing plants. Overall, these results contribute to the further understanding of the TaERF-6-3A gene function in wheat.
Emerging New Biomarkers for Cardiovascular Disease
Authors: Rochette Luc
Published: March 2022

In this Special Issue of the International Journal of Molecular Sciences, we include insightful reviews and research papers on the subject “Emerging New Biomarkers for Cardiovascular Disease” [...]
Controlling the Phase Behavior and Reflection of Main-Chain Cholesteric Oligomers Using a Smectic Monomer
Authors: Yue Lansong , Shi Xiuyi , Zhou Guofu , de Haan Laurens T.
Published: March 2022

Cholesteric liquid crystals (CLCs) are a significant class of temperature-responsive photonic materials that have the ability to selectively reflect light of a specific wavelength. However, the fabrication of main-chain CLC oligomers with dramatic reflection band variation upon varying the temperatures remains a challenge. Here, a feasible method for improving and controlling the responsiveness of main-chain cholesteric liquid crystal oligomers by the incorporation of a smectic monomer is reported. The smectic monomer strengthens the smectic character of the oligomers and enhances the magnitude of the change of the pitch as a function of temperature upon approaching the cholesteric–smectic phase transition temperature. The central wavelength of the reflection band can be easily modified by mixing in an additional chiral dopant. This promising method will open the door to the preparation of temperature-responsive photonic devices with excellent responsiveness.