bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Hydrogen and Synthetic Natural Gas within Legacy Power Generation Facilities
Authors: Dominguez-Gonzalez German , Muñoz-Hernandez Jose Ignacio , Bunn Derek , Garcia-Checa Carlos Jesus
Published: June 2022

Whilst various new technologies for power generation are continuously being evaluated, the owners of almost-new facilities, such as combined-cycle gas turbine (CCGT) plants, remain motivated to adapt these to new circumstances and avoid the balance-sheet financial impairments of underutilization. Not only are the owners reluctant to decommission the legacy CCGT assets, but system operators value the inertia and flexibilities they contribute to a system becoming predominated with renewable generation. This analysis therefore focuses on the reinvestment cases for adapting CCGT to hydrogen (H2), synthetic natural gas (SNG) and/or retrofitted carbon capture and utilization systems (CCUS). Although H2, either by itself or as part of SNG, has been evaluated attractively for longer-term electricity storage, the business case for how it can be part of a hybrid legacy CCGT system has not been analyzed in a market context. This work compares the power to synthetic natural gas to power (PSNGP) adaptation with the simpler and less expensive power to hydrogen to power (P2HP) adaptation. Both the P2HP and PSNGP configurations are effective in terms of decarbonizations. The best results of the feasibility analysis for a UK application with low CCGT load factors (around 31%) were obtained for 100% H2 (P2HP) in the lower range of wholesale electricity prices (less than 178 GBP/MWh), but in the higher range of prices, it would be preferable to use the PSNGP configuration with a low proportion of SNG (25%). If the CCGT load factor increased to 55% (the medium scenario), the breakeven profitability point between P2HP and PSNGP decreased to a market price of 145 GBP/MWh. Alternatively, with the higher load factors (above 77%), satisfactory results were obtained for PSNGP using 50% SNG if with market prices above 185 GBP/MWh.
Improving the Efficiency of Oil Recovery in Research and Development
Authors: Kremieniewski Marcin
Published: June 2022

By creating a special edition entitled Fundamentals of Enhanced Oil Recovery, the editors focus on the problem of the global increase in energy demand [...]
Performance Evaluation of Convolutional Auto Encoders for the Reconstruction of Li-Ion Battery Electrode Microstructure
Authors: Faraji Niri Mona , Mafeni Mase Jimiama , Marco James
Published: June 2022

Li-ion batteries play a critical role in the transition to a net-zero future. The discovery of new materials and the design of novel microstructures for battery electrodes is necessary for the acceleration of this transition. The battery electrode microstructure can potentially reveal the cells’ electrochemical characteristics in great detail. However, revealing this relation is very challenging due to the high dimensionality of the problem and the large number of microstructure features. In fact, it cannot be achieved via the traditional trial-and-error approaches, which are associated with significant cost, time, and resource waste. In search for a systematic microstructure analysis and design method, this paper aims at quantifying the Li-ion battery electrode structural characteristics via deep learning models. Deliberately, here, a methodology and framework are developed to reveal the hidden microstructure characteristics via 2D and 3D images through dimensionality reduction. The framework is based on an auto-encoder decoder for microstructure reconstruction and feature extraction. Unlike most of the existing studies that focus on a limited number of features extracted from images, this study concentrates directly on the images and has the potential to define the number of features to be extracted. The proposed methodology and model are computationally effective and have been tested on a real open-source dataset where the results show the efficiency of reconstruction and feature extraction based on the training and validation mean squared errors between 0.068 and 0.111 and from 0.071 to 0.110, respectively. This study is believed to guide Li-ion battery scientists and manufacturers in the design and production of next generation Li-ion cells in a systematic way by correlating the extracted features at the microstructure level and the cell’s electrochemical characteristics.
The Sense and Non-Sense of PEDs—Feeding Back Practical Experiences of Positive Energy District Demonstrators into the European PED Framework Definition Development Process
Authors: Vandevyvere Han , Ahlers Dirk , Wyckmans Annemie
Published: June 2022

This article discusses early developments of the Positive Energy District (PED) concept, both in terms of its definition and of its implementation in real world demonstrators. Based on the specific challenges for creating an operational definition for the European +CityxChange project, the feasibility of creating a PED was practically explored by identifying 4 possible subtypes that respond to varying constraints regarding the energy balance of the PED. This article provides the context and describes these 4 ambitions levels: PEDautonomous, PEDdynamic, PEDvirtual, and PrePED; and the 3 boundary modes: geographical, functional, and virtual. The work thus expands on the first general PED definitions as they were put forward in the SET-plan and by the European Commission, while allowing a better response to the specific boundary conditions of PEDs’ physical context. As such, it provides an operational, city-focused, bottom-up PED definition. The present study analyses how these efforts connect to current work being performed on the development of a European PED Framework Definition. In the latter, new elements such as context factors are introduced in order to account for the varying boundary conditions that PEDs must address, and in particular the difficulties of realising PEDs in existing and densely built-up urban areas. Hereby it can be argued that the approach with 4 subtypes is a bottom-up method of addressing the same challenges as a context factor based approach operating in a top-down manner, this time starting from the regional or national renewable energy potentials. Both approaches indeed strive towards an optimum setup of PEDs both within their geographical boundaries and in their interactions with the surrounding energy infrastructures and cities. These efforts are instrumental in helping to prevent that a PED is being regarded as a goal in se, functionally disconnected from its surroundings. There are strong arguments in favour of handling PEDs as building blocks for the broader realisation of carbon neutral cities and regions, thus contributing to the systemic change that is needed to futureproof the built environment as a whole. Without applying this integrating perspective, PEDs risk creating a sub-optimal lock-in within their sites and thus remain one-off experiments, lacking connection to the wider urban sustainability strategies that are needed to properly address today’s energy and climate emergencies. This holds even more when considering the quality-related requirements that come with sustainable urban design and governance. Therefore, this study further explores how PEDs can fully support such a deep urban sustainability transition, and what could consequently be the next steps towards successful and upscaled PED deployment.
What Can Game Theory Tell Us about an AI ‘Theory of Mind’?
Authors: Harré Michael S.
Published: June 2022

Game theory includes a rich source of methods for analysing strategic interactions where there are a small number of agents, each having only a few choices. In more complex settings though, where there are many choices over indefinite time horizons involving large social groups, these methods are unlikely to fully capture the causes of agent behaviour. If agents are able to simplify the task of understanding what others might do by modelling the constraints of others, particularly unobservable cognitive constraints, then the possible behavioural outcomes can be similarly restricted, thereby reducing the complexity of a social interaction. Having a cognitive representation of the unobserved causal states of others is an aspect of a ‘Theory of Mind’ and it plays a central role in the psychology of social interactions. In this article I examine a selection of results on the theory of mind and connect these with the ‘game theory of mind’ to draw conclusions regarding the complexity of one-on-one and large-scale social coordination. To make this explicit, I will illustrate the relationship between the two psychological terms ‘introspection’ and ‘theory of mind’ and the economic analysis of game theory, while retaining as much as possible of the richness of the psychological concepts. It will be shown that game theory plays an important role in modelling interpersonal relationships for both biological and artificial agents, but it is not yet the whole story, and some psychological refinements to game theory are discussed.
Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus
Authors: Hearn Jack , Riveron Jacob M. , Irving Helen , Weedall Gareth D. , Wondji Charles S.
Published: June 2022

Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of An. funestus, with an average πn of 0.027 versus a genome-wide average of 0.002, and πn is consistently high in populations across Africa. Elevated APL1 diversity was consistent between the independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide resistance was observed. Although lacking the diversity of APL1, two further mosquito innate-immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. The cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, a result discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogues, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. In conclusion, we hypothesize that higher gene expression of APL1 than its paralogues is correlated with a more open chromatin formation, which enhances gene conversion and elevated diversity at this locus.
The Impact of Sociodemographic Characteristics on Coping Strategies Used by Nurses Working at COVID and Non-COVID Hospital Departments during COVID-19 Pandemic: A Cross-Sectional Study
Authors: Dolić Matea , Antičević Vesna , Dolić Krešimir , Pogorelić Zenon
Published: June 2022

Background: The aim of our study was to compare coping strategies applied by nurses working during the COVID-19 pandemic at COVID-19 (CoV) and non-COVID-19 (non-CoV) hospital departments with regards to their sociodemographic characteristics in order that the system can provide them better support in future similar situations. Methods: A total of 380 out of 1305 nurses participated in the survey during December 2020. Coping Inventory for Stressful Situations (CISS) was used. Stepwise regression analysis was used to determine the interaction between sociodemographic characteristics and coping strategies. Results: The CoV married nurses (62.2%) used problem- (p = 0.010) and emotion- (p = 0.003) focused coping more and avoidance coping less (p = 0.007). CoV nurses with master’s degrees (11.1%) used both problem- and emotion-focused coping less (p < 0.01), and older nurses used emotional coping more than the younger nurses (p = 0.027), whereas younger nurses used more avoidance coping (p < 0.01). CoV nurses without children (41%) used avoidance strategies more than nurses who had 2–3 children (p < 0.001). Among non-CoV nurses, less use of emotional coping was recorded in nurses with master’s degrees (4%) than in those with a high school diploma (44.2%) (p = 0.002). Avoidance coping was also used more by married non-CoV nurses (79.1%) (p < 0.001) and those without children (p < 0.001). Conclusions: Sociodemographic factors such as working experience, age, level of education and marital status influenced chosen coping strategies during the health crisis.
Early Oxygen Treatment Measurements Can Predict COVID-19 Mortality: A Preliminary Study
Authors: Levi Yosi , Yamin Dan , Brandes Tomer , Shmueli Erez , Patalon Tal , Peretz Asaf , Gazit Sivan , Nahir Barak
Published: June 2022

Halting the rapid clinical deterioration, marked by arterial hypoxemia, is among the greatest challenges clinicians face when treating COVID-19 patients in hospitals. While it is clear that oxygen measures and treatment procedures describe a patient’s clinical condition at a given time point, the potential predictive strength of the duration and extent of oxygen supplementation methods over the entire course of hospitalization for a patient death from COVID-19 has yet to be assessed. In this study, we aim to develop a prediction model for COVID-19 mortality in hospitals by utilizing data on oxygen supplementation modalities of patients. We analyzed the data of 545 patients hospitalized with COVID-19 complications admitted to Assuta Ashdod Medical Center, Israel, between 7 March 2020, and 16 March 2021. By solely analyzing the daily data on oxygen supplementation modalities in 182 random patients, we could identify that 75% (9 out of 12) of individuals supported by reservoir oxygen masks during the first two days died 3–30 days following hospital admission. By contrast, the mortality rate was 4% (4 out of 98) among those who did not require any oxygenation supplementation. Then, we combined this data with daily blood test results and clinical information of 545 patients to predict COVID-19 mortality. Our Random Forest model yielded an area under the receiver operating characteristic curve (AUC) score on the test set of 82.5%, 81.3%, and 83.0% at admission, two days post-admission, and seven days post-admission, respectively. Overall, our results could essentially assist clinical decision-making and optimized treatment and management for COVID-19 hospitalized patients with an elevated risk of mortality.
Psychometric Properties and Effects on Health Outcomes of the Patient Assessment of Chronic Illness Care (PACIC) in Korean Hemodialysis Patients
Authors: Seo Ae-Rim , Kim Bo-Kyoung , Park Ki-Soo
Published: June 2022

Background: The satisfaction of patients receiving integrated care with End-Stage Renal Disease (ESRD) is widely advocated and patients with ESRD have special health needs, but few studies have investigated whether integrated care was associated with health outcomes. Our aims were to evaluate the psychometric properties of the Korean-translated patient assessment of chronic illness care (PACIC) in patients with ESRD, and to evaluate whether PACIC evaluated by patients was associated with health outcomes. Methods: ESRD patients on hemodialysis (n = 172) at 2 dialysis centers. Data quality, internal consistency and correlation between items and scales were assessed. To test the external validity, the association between PACIC and the health behaviour and outcomes of hemodialysis patients was analyzed. Results: The mean score of the PACIC items was 3.0. The item-scale correlation (0.67–0.85) and test-retest correlation (0.72–0.82) regarding scales for internal consistency showed excellent consistency. Total PACIC score was significantly associated with dietary self-efficacy (β = 0.22) and serum potassium (Exp(B) = 1.65). Higher overall PACIC score was significantly associated with higher physical health status (β = 3.52). Conclusions: The Korean-translated PACIC questionnaire is a tool with reliability and validity. Comprehensive treatment strategies for ESRD patients may improve their health behaviors and outcomes.
The Fellini Museum of Rimini in Italy and the Genetic Algorithms-Based Method to Optimize the Design of an Integrated System Network and Installations
Authors: Garzia Fabio
Published: June 2022

The Fellini Museum is an exhibition hall dedicated to the Rimini film director Federico Fellini, included by the Ministry of Culture of Italy among the great national cultural projects. It was inaugurated on 19 August 2021, and it is the first worldwide exhibition hall dedicated to the famous film director. The museum, intended as a widespread museum center, is divided into three separate places in the historic center of Rimini: Sismondo Castle (built at the behest of Sigismondo Malatesta, at that time Lord of Rimini and Fano, starting from 1437 AD), Fulgor Palace and Malatesta square. The goal of the present paper is double. In the first part, as a case study, the innovative integrated system and installations planned for the optimal functioning and management of the Fellini Museum of Rimini in Italy is illustrated, showing its related complexity, due to its extension and articulation through different environments and due to the respect for architectural/historical heritage. In the second part, as dedicated and linked research, a proper Genetic Algorithms-based method, studied and applied for the optimization of the design of the wired network of the integrated system, the electrical power network and the air conditioning network is illustrated. It guarantees a decrease of realization costs, considering also the typical vincula and restrictions of already existing historical buildings, such as the considered one.
Real-Time Detection of the Nutritional Compounds in Green ‘Ratuni UNPAD’ Cayenne Pepper
Authors: Kusumiyati Kusumiyati , Putri Ine Elisa , Hamdani Jajang Sauman , Suhandy Diding
Published: June 2022

The detection of nutritional compounds is usually performed through laboratory analysis, which requires extensive planning, time, cost, and effort. Alternatively, visible/near-infrared (Vis/NIR) spectroscopy can be used to determine the presence of nutritional compounds in real-time. This study aimed to investigate the potential application of the Vis/NIR spectroscopy in the quantitative detection of nutritional compounds in green ‘Ratuni UNPAD’ cayenne pepper. Prior to the model development, 80 samples were prepared for the calibration set, while another 40 samples were provided for the prediction set. Subsequently, the parameters used to calculate the model accuracy included the coefficient of correlation in calibration set (Rcal), coefficient of correlation in prediction set (Rpred), root mean square error of calibration set (RMSEC), root mean square error of prediction set (RMSEP) and the ratio of prediction to deviation (RPD). The experimental results involving the total carotenoids showed good model indicators with Rcal, Rpred, RMSEC, RMSEP, and RPD at 0.94, 0.89, 1.29, 1.75, and 2.21, respectively. Additionally, the analysis of the water content indicated Rcal, Rpred, RMSEC, RMSEP, and RPD values of 0.86, 0.85, 0.59, 0.61, and 1.90, respectively, while that of capsaicin had Rcal, Rpred, RMSEC, RMSEP, and RPD values of 0.89, 0.90, 117.82, 115.62, and 2.29, respectively. The results showed that Vis/NIR spectroscopy can be used to detect the nutritional compounds in green ‘Ratuni UNPAD’ cayenne pepper based on total carotenoids, water content, and capsaicin parameters.
Influence of the Thickness of the Seasonally Thawed Layer of Permafrost in the Eastern Siberia Catchments on the Content of Organic Matter in River Waters
Authors: Gabysheva Olga I. , Gabyshev Viktor A. , Barinova Sophia , Yakshina Irina A. , Pavlov Innokentiy S.
Published: June 2022

In the context of global climate change, a significant increase in the active layer thickness (ALT) of permafrost is expected in the current century. This process has been observed by researchers over the past few decades. If the current climate trend continues, an increase in ALT may have a significant impact on the concentration of organic matter in Arctic river waters. The relationship between the thickness of the seasonally thawed layer of permafrost and the concentration of dissolved organic matter in river waters has been explored using clustering, one-way ANOVA, and cross-tabulation analysis. The data set for analysis included original details on the content of organic matter in the rivers of Eastern Siberia (in terms of COD, BOD5, and the color of the water), phytoplankton abundance and biomass, and data on the permafrost active layer thickness (ALT) in the catchments. It was revealed that in the areas of catchments where the ALT is deeper, the content of organic matter in the rivers is lower than in areas with a shallow, seasonally thawed permafrost. Our results are consistent with the existing conceptual model of the influence of ALT on the chemistry of river waters in the cryolithozone. This knowledge is important for predicting the chemical composition of the Arctic rivers, eutrophication, and the rate of inflow of dissolved solids into the Arctic Ocean under the current conditions of ALT deepening.
Anxiety towards COVID-19, Fear of Negative Appearance, Healthy Lifestyle, and Their Relationship with Well-Being during the Pandemic: A Cross-Cultural Study between Indonesia and Poland
Authors: Novita Shally , Andriani Dhini , Erika  , Lipowski Mariusz , Lipowska Małgorzata
Published: June 2022

The COVID-19 pandemic has led to massive changes in almost all aspects of human life, including emotional states such as anxiety and fear, perspectives about healthy lifestyles, and psychological outcomes. This study aimed to disentangle the mechanisms that underlie the relationships of anxiety towards COVID-19 and fear of negative appearance with well-being, we also investigated the effects of cultural variations on levels of anxiety, fear of negative appearance, healthy lifestyles, and well-being. A total of 881 Indonesians (n = 172) and Poles (n = 709) participated in this study. Participants completed self-report measures of psychological well-being, anxiety, fear of negative appearance, compulsive exercise, and eating disorders. Multigroup structural equation modelling (SEM) was used. The results showed no statistically meaningful relationship between anxiety towards COVID-19 and well-being. However, it was found that, in the Polish sample, compulsive exercise and eating disorders mediated the relationship between fear of negative appearance and well-being. Cultural differences were also found in the mean scores of all examined constructs, with eating disorders being an exception. Therefore, this study highlights cultural aspects that determine emotional states, healthy lifestyles, and well-being.
Gait Alteration Due to Haemophilic Arthropathies in Patients with Moderate Haemophilia
Authors: Fouasson-Chailloux Alban , Leboeuf Fabien , Maugars Yves , Trossaert Marc , Menu Pierre , Rannou François , Vinatier Claire , Guicheux Jérome , Gross Raphael , Dauty Marc
Published: June 2022

Some patients with moderate haemophilia (PWMH) report joint damage potentially responsible for gait disorders. Three-dimensional gait analysis (3DGA) is a relevant tool for the identification of complex musculoskeletal impairment. We performed an evaluation with 3DGA of 24 PWMH aged 44.3 ± 16.1 according to their joint status [Haemophilia Joint Health Score (HJHS) < 10 or HJHS ≥ 10] and assessed the correlation with the radiological and clinical parameters. Sixteen had HJHS < 10 (group 1) and eight had HJHS ≥ 10 (group 2). They were compared to 30 healthy subjects of a normative dataset. Both knee and ankle gait variable scores were increased in group 2 compared to the controls (p = 0.02 and p = 0.04, respectively). The PWMH of group 2 had a significant increase in their stance phase, double support duration, and stride width compared to the controls and group 1 (p < 0.01). Very low correlations were found for the ankle gait variable score with the ankle Pettersson sub-score (r2 = 0.250; p = 0.004) and ankle HJHS sub-score (r2 = 0.150; p = 0.04). For the knee, very low correlation was also found between the knee gait variable score and its HJHS sub-score (r2 = 0.290; p < 0.0001). Patients with moderate haemophilia presented a gait alteration in the case of poor lower limb joint status.
Improvements of Warning Signs for Black Ice Based on Driving Simulator Experiments
Authors: Lee Ghangshin , Hwang Sooncheon , Lee Dongmin
Published: June 2022

Black ice is one of the main causes of traffic accidents in winter, and warning signs for black ice are generally ineffective because of the lack of credible information. To overcome this limitation, new warning signs for black ice were developed using materials that change color in response to different temperatures. The performance and effects of the new signs were investigated by conducting driver behavior analysis. To this end, driving simulator experiments were conducted with 37 participants for two different rural highway sections, i.e., a curve and a tangent. The analysis results of the driving behavior and visual behavior experiments showed that the conventional signs had insufficient performance in terms of inducing changes in driving behavior for safety. Meanwhile, the new signs actuated by weather conditions offered a statistically significant performance improvement. Typically, driver showed two times higher speed deceleration when they fixed eyes on the new weather-actuated warning sign (12.80 km/h) compared to the conventional old warning sign (6.84 km/h) in the curve segment. Accordingly, this study concluded that the new weather-actuated warning signs for black ice are more effective than the conventional ones for accident reduction during winters.
Pesticide Exposure in Relation to the Incidence of Abnormal Glucose Regulation: A Retrospective Cohort Study
Authors: Kim Sung-Kyung , Oh Hyun-Jung , Oh Sung-Soo , Koh Sang-Baek
Published: June 2022

Diabetes and prediabetes (called abnormal glucose regulation (AGR)) are adverse health effects associated with exposure to pesticides. However, there are few epidemiological studies on the relationship between pesticide use and the incidence of AGR. We examined the causal relationship between pesticide use and AGR incidence in a rural population using data from a Korean Farmers’ Cohort study of 1076 participants. Poisson regression with robust error variance was used to calculate the relative risks (RR) and 95% confidence intervals (CI) to estimate the relationship between pesticide exposure and AGR. The incidence of AGR in the pesticide-exposed group was 29.1%. Pesticide use increased the RR of AGR (RR 1.32, 95% CI 1.03–1.69). We observed a low-dose effect related to exposure of pesticides to AGR and a U-shaped dose–response relationship in men. Pesticide exposure is related to the incidence of AGR, and the causal relationship differs between men and women.
Crosstalk between MicroRNA and Oxidative Stress in Physiology and Pathology 2.0
Authors: Fioravanti Antonella , Giordano Antonio , Dotta Francesco , Pirtoli Luigi
Published: June 2022

MicroRNAs (miRNAs) are a class of small non-coding RNAs around 22 nucleotides long that regulate gene expression by binding specific sequences within target messenger RNA (mRNA) [...]
Design and Development of a Bimodal Optical Instrument for Simultaneous Vibrational Spectroscopy Measurements
Authors: Arévalo Laura A. , O’Brien Stephen A. , Lopez Eneko , Singh Gajendra Pratap , Seifert Andreas
Published: June 2022

Vibrational spectroscopy techniques are widely used in analytical chemistry, physics and biology. The most prominent techniques are Raman and Fourier-transform infrared spectroscopy (FTIR). Combining both techniques delivers complementary information of the test sample. We present the design, construction, and calibration of a novel bimodal spectroscopy system featuring both Raman and infrared measurements simultaneously on the same sample without mutual interference. The optomechanical design provides a modular flexible system for solid and liquid samples and different configurations for Raman. As a novel feature, the Raman module can be operated off-axis for optical sectioning. The calibrated system demonstrates high sensitivity, precision, and resolution for simultaneous operation of both techniques and shows excellent calibration curves with coefficients of determination greater than 0.96. We demonstrate the ability to simultaneously measure Raman and infrared spectra of complex biological material using bovine serum albumin. The performance competes with commercial systems; moreover, it presents the additional advantage of simultaneously operating Raman and infrared techniques. To the best of our knowledge, it is the first demonstration of a combined Raman-infrared system that can analyze the same sample volume and obtain optically sectioned Raman signals. Additionally, quantitative comparison of confocality of backscattering micro-Raman and off-axis Raman was performed for the first time.
Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome
Authors: Ermolenko Elena , Simanenkova Anna , Voropaeva Lyubov , Lavrenova Nadezhda , Kotyleva Maryna , Minasian Sarkis , Chernikova Alena , Timkina Natalya , Gladyshev Nikita , Dmitriev Alexander , Suvorov Alexander , Galagudza Michael , Karonova Tatiana
Published: June 2022

Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.
Genome-Wide Studies in Ischaemic Stroke: Are Genetics Only Useful for Finding Genes?
Authors: Gallego-Fabrega Cristina , Muiño Elena , Cárcel-Márquez Jara , Llucià-Carol Laia , Lledós Miquel , Martín-Campos Jesús M. , Cullell Natalia , Fernández-Cadenas Israel
Published: June 2022

Ischaemic stroke is a complex disease with some degree of heritability. This means that heritability factors, such as genetics, could be risk factors for ischaemic stroke. The era of genome-wide studies has revealed some of these heritable risk factors, although the data generated by these studies may also be useful in other disciplines. Analysis of these data can be used to understand the biological mechanisms associated with stroke risk and stroke outcome, to determine the causality between stroke and other diseases without the need for expensive clinical trials, or to find potential drug targets with higher success rates than other strategies. In this review we will discuss several of the most relevant studies regarding the genetics of ischaemic stroke and the potential use of the data generated.
Release Kinetics and In Vitro Characterization of Sodium Percarbonate and Calcium Peroxide to Oxygenate Bioprinted Tissue Models
Authors: Ke Dongxu , Kengla Carlos , Lee Sang Jin , Yoo James J. , Zhu Xuesong , Murphy Sean Vincent
Published: June 2022

Oxygen-generating materials have been used in several tissue engineering applications; however, their application as in situ oxygen supply within bioprinted constructs has not been deeply studied. In this study, two oxygen-generating materials, sodium percarbonate (SPO) and calcium peroxide (CPO), were studied for their oxygen release kinetics under a 0.1% O2 condition. In addition, a novel cell-culture-insert setup was used to evaluate the effects of SPO and CPO on the viability of skeletal muscle cells under the same hypoxic condition. Results showed that SPO had a burst oxygen release, while CPO had a more stable oxygen release than SPO. Both SPO and CPO reduced cell viability when used alone. The addition of catalase in SPO and CPO increased the oxygen release rate, as well as improving the viability of skeletal muscle cells; however, CPO still showed cytotoxicity with catalase. Additionally, the utilization of 1 mg/mL SPO and 20 U catalase in a hydrogel for bioprinting significantly enhanced the cell viability under the hypoxic condition. Moreover, bioprinted muscle constructs could further differentiate into elongated myotubes when transferring back to the normoxic condition. This work provides an excellent in vitro model to test oxygen-generating materials and further discover their applications in bioprinting, where they represent promising avenues to overcome the challenge of oxygen shortage in bioprinted constructs before their complete vascularization.
Invertebrate Models in Innate Immunity and Tissue Remodeling Research
Authors: La Corte Claudia , Baranzini Nicolò , Grimaldi Annalisa , Parisi Maria Giovanna
Published: June 2022

The aim of this Special Issue is to highlight the close functional and highly conserved link between innate immunity, homeostasis maintenance, inflammation, tissue remodeling and regeneration [...]
A Small Molecule That Promotes Cellular Senescence Prevents Fibrogenesis and Tumorigenesis
Authors: Meang Moon Kee , Kim Saesbyeol , Kim Ik-Hwan , Kim Han-Soo , Youn Byung-Soo
Published: June 2022

Uncontrolled proliferative diseases, such as fibrosis or cancer, can be fatal. We previously found that a compound containing the chromone scaffold (CS), ONG41008, had potent antifibrogenic effects associated with EMT or cell-cycle control resembling tumorigenesis. We investigated the effects of ONG41008 on tumor cells and compared these effects with those in pathogenic myofibroblasts. Stimulation of A549 (lung carcinoma epithelial cells) or PANC1 (pancreatic ductal carcinoma cells) with ONG41008 resulted in robust cellular senescence, indicating that dysregulated cell proliferation is common to fibrotic cells and tumor cells. The senescence was followed by multinucleation, a manifestation of mitotic slippage. There was significant upregulation of expression and rapid nuclear translocation of p-TP53 and p16 in the treated cancer cells, which thereafter died after 72 h confirmed by 6 day live imaging. ONG41008 exhibited a comparable senogenic potential to that of dasatinib. Interestingly, ONG41008 was only able to activate caspase-3, 7 in comparison with quercetin and fisetin, also containing CS in PANC1. ONG41008 did not seem to be essentially toxic to normal human lung fibroblasts or primary prostate epithelial cells, suggesting ONG41008 can distinguish the intracellular microenvironment between normal cells and aged or diseased cells. This effect might occur as a result of the increased NAD/NADH ratio, because ONG41008 restored this important metabolic ratio in cancer cells. Taken together, this is the first study to demonstrate that a small molecule can arrest uncontrolled proliferation during fibrogenesis or tumorigenesis via both senogenic and senolytic potential. ONG41008 could be a potential drug for a broad range of fibrotic or tumorigenic diseases.
Nurr1 Is Not an Essential Regulator of BDNF in Mouse Cortical Neurons
Authors: Abdollahi Mona , Fahnestock Margaret
Published: June 2022

Nurr1 and brain-derived neurotrophic factor (BDNF) play major roles in cognition. Nurr1 regulates BDNF in midbrain dopaminergic neurons and cerebellar granule cells. Nurr1 and BDNF are also highly expressed in the cerebral cortex, a brain area important in cognition. Due to Nurr1 and BDNF tissue specificity, the regulatory effect of Nurr1 on BDNF in different brain areas cannot be generalized. The relationship between Nurr1 and BDNF in the cortex has not been investigated previously. Therefore, we examined Nurr1-mediated BDNF regulation in cortical neurons in activity-dependent and activity-independent states. Mouse primary cortical neurons were treated with the Nurr1 agonist, amodiaquine (AQ). Membrane depolarization was induced by KCl or veratridine and reversed by nimodipine. AQ and membrane depolarization significantly increased Nurr1 (p < 0.001) and BDNF (pAQ < 0.001, pKCl < 0.01) as assessed by real-time qRT-PCR. However, Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized neurons. Accordingly, the positive correlation between Nurr1 and BDNF expression in AQ and membrane depolarization experiments does not imply co-regulation because Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized cortical neurons. Therefore, in contrast to midbrain dopaminergic neurons and cerebellar granule cells, Nurr1 does not regulate BDNF in cortical neurons.
Solid-State Construction of CuOx/Cu1.5Mn1.5O4 Nanocomposite with Abundant Surface CuOx Species and Oxygen Vacancies to Promote CO Oxidation Activity
Authors: Liu Baolin , Wu Hao , Li Shihao , Xu Mengjiao , Cao Yali , Li Yizhao
Published: June 2022

Carbon monoxide (CO) oxidation performance heavily depends on the surface-active species and the oxygen vacancies of nanocomposites. Herein, the CuOx/Cu1.5Mn1.5O4 were fabricated via solid-state strategy. It is manifested that the construction of CuOx/Cu1.5Mn1.5O4 nanocomposite can produce abundant surface CuOx species and a number of oxygen vacancies, resulting in substantially enhanced CO oxidation activity. The CO is completely converted to carbon dioxide (CO2) at 75 °C when CuOx/Cu1.5Mn1.5O4 nanocomposites were involved, which is higher than individual CuOx, MnOx, and Cu1.5Mn1.5O4. Density function theory (DFT) calculations suggest that CO and O2 are adsorbed on CuOx/Cu1.5Mn1.5O4 surface with relatively optimal adsorption energy, which is more beneficial for CO oxidation activity. This work presents an effective way to prepare heterogeneous metal oxides with promising application in catalysis.
Orchestrated Action of AMPK Activation and Combined VEGF/PD-1 Blockade with Lipid Metabolic Tunning as Multi-Target Therapeutics against Ovarian Cancers
Authors: Yung Mingo M. H. , Siu Michelle K. Y. , Ngan Hextan Y. S. , Chan David W. , Chan Karen K. L.
Published: June 2022

Ovarian cancer is one of the most lethal gynecological malignancies worldwide, and chemoresistance is a critical obstacle in the clinical management of the disease. Recent studies have suggested that exploiting cancer cell metabolism by applying AMP-activated protein kinase (AMPK)-activating agents and distinctive adjuvant targeted therapies can be a plausible alternative approach in cancer treatment. Therefore, the perspectives about the combination of AMPK activators together with VEGF/PD-1 blockade as a dual-targeted therapy against ovarian cancer were discussed herein. Additionally, ferroptosis, a non-apoptotic regulated cell death triggered by the availability of redox-active iron, have been proposed to be governed by multiple layers of metabolic signalings and can be synergized with immunotherapies. To this end, ferroptosis initiating therapies (FITs) and metabolic rewiring and immunotherapeutic approaches may have substantial clinical potential in combating ovarian cancer development and progression. It is hoped that the viewpoints deliberated in this review would accelerate the translation of remedial concepts into clinical trials and improve the effectiveness of ovarian cancer treatment.
Nano–Liposomes Double Loaded with Curcumin and Tetrandrine: Preparation, Characterization, Hepatotoxicity and Anti–Tumor Effects
Authors: Song Jia-Wen , Liu Yu-Shi , Guo Yu-Rou , Zhong Wen-Xiao , Guo Yi-Ping , Guo Li
Published: June 2022

(1) Background: Curcumin (CUR) and tetrandrine (TET) are natural compounds with various bioactivities, but have problems with low solubility, stability, and absorption rate, resulting in low bioavailability, and limited applications in food, medicine, and other fields. It is very important to improve the solubility while maintaining the high activity of drugs. Liposomes are micro–vesicles synthesized from cholesterol and lecithin. With high biocompatibility and biodegradability, liposomes can significantly improve drug solubility, efficacy, and bioavailability. (2) Methods: In this work, CUR and TET were encapsulated with nano–liposomes and g DSPE–MPEG 2000 (DP)was added as a stabilizer to achieve better physicochemical properties, biosafety, and anti–tumor effects. (3) Results: The nano–liposome (CT–DP–Lip) showed stable particle size (under 100 nm) under different conditions, high solubility, drug encapsulation efficiency (EE), loading capacity (LC), release rate in vitro, and stability. In addition, in vivo studies demonstrated CT–DP–Lip had no significant toxicity on zebrafish. Tumor cytotoxicity test showed that CT–DP–Lip had a strong inhibitory effect on a variety of cancer cells. (4) Conclusions: This work showed that nano–liposomes can significantly improve the physical and chemical properties of CUR and TET and make them safer and more efficient.
AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin
Authors: Geoffroy Marine , Lemesle Marine , Kleinclauss Alexandra , Mazerbourg Sabine , Batista Levy , Barberi-Heyob Muriel , Bastogne Thierry , Boireau Wilfrid , Rouleau Alain , Dupommier Dorian , Boisbrun Michel , Comoy Corinne , Flament Stéphane , Grillier-Vuissoz Isabelle , Kuntz Sandra
Published: June 2022

Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ and AB186. Previous studies showed that both compounds induce apoptosis, nevertheless AB186 was a more potent agent. The kinetic of cellular events was investigated by real-time cell analysis system (RTCA) in MCF-7 (hormone dependent) and MDA-MB-231 (triple negative) breast cancer (TNBC) cells, followed by cell morphology analysis by immuno-localization. Both compounds induced a rapid modification of both impedance-based signals and cellular morphology. This process was associated with an inhibition of cell migration measured by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cells. In order to identify cytoplasmic targets of AB186, we performed surface plasmon resonance (SPR) and pull-down analyses. Subsequently, 6 cytoskeleton components were identified as potential targets. We further validated α-tubulin as one of the direct targets of AB186. In conclusion, our results suggested that AB186 could be promising to develop novel therapeutic strategies to treat aggressive forms of breast cancer such as TNBC.
RNA Polymerase II Transcription in Pneumocystis: TFIIB from Pneumocystis carinii Can Replace the Transcriptional Functions of Fission Yeast Schizosaccharomyces pombe TFIIB In Vivo and In Vitro
Authors: Rojas Diego A. , Urbina Fabiola , Solari Aldo , Maldonado Edio
Published: June 2022

The Pneumocystis genus is an opportunistic fungal pathogen that infects patients with AIDS and immunocompromised individuals. The study of this fungus has been hampered due to the inability to grow it in a (defined media/pure) culture. However, the use of modern molecular techniques and genomic analysis has helped researchers to understand its complex cell biology. The transcriptional process in the Pneumocystis genus has not been studied yet, although it is assumed that it has conventional transcriptional machinery. In this work, we have characterized the function of the RNA polymerase II (RNAPII) general transcription factor TFIIB from Pneumocystis carinii using the phylogenetically related biological model Schizosaccharomyces pombe. The results of this work show that Pneumocystis carinii TFIIB is able to replace the essential function of S. pombe TFIIB both in in vivo and in vitro assays. The S. pombe strain harboring the P carinii TFIIB grew slower than the parental wild-type S. pombe strain in complete media and in minimal media. The S. pombe cells carrying out the P. carinii TFIIB are larger than the wild-type cells, indicating that the TFIIB gene replacement confers a phenotype, most likely due to defects in transcription. P. carinii TFIIB forms very weak complexes with S. pombe TATA-binding protein on a TATA box promoter but it is able to form stable complexes in vitro when S. pombe TFIIF/RNAPII are added. P. carinii TFIIB can also replace the transcriptional function of S. pombe TFIIB in an in vitro assay. The transcription start sites (TSS) of the endogenous adh gene do not change when P. carinii TFIIB replaces S. pombe TFIIB, and neither does the TSS of the nmt1 gene, although this last gene is poorly transcribed in vivo in the presence of P. carinii TFIIB. Since transcription by RNA polymerase II in Pneumocystis is poorly understood, the results described in this study are promising and indicate that TFIIB from P. carinii can replace the transcriptional functions of S. pombe TFIIB, although the cells expressing the P. carini TFIIB show an altered phenotype. However, performing studies using a heterologous approach, like this one, could be relevant to understanding the basic molecular processes of Pneumocystis such as transcription and replication.
Short-Term, Voluntary Exercise Affects Morpho-Functional Maturation of Adult-Generated Neurons in Rat Hippocampus
Authors: Lattanzi Davide , Savelli David , Pagliarini Marica , Cuppini Riccardo , Ambrogini Patrizia
Published: June 2022

Physical exercise is a well-proven neurogenic stimulus, promoting neuronal progenitor proliferation and affecting newborn cell survival. Besides, it has beneficial effects on brain health and cognition. Previously, we found that three days of physical activity in a very precocious period of adult-generated granule cell life is able to antedate the appearance of the first GABAergic synaptic contacts and increase T-type Ca2+ channel expression. Considering the role of GABA and Ca2+ in fostering neuronal maturation, in this study, we used short-term, voluntary exercise on a running wheel to investigate if it is able to induce long-term morphological and synaptic changes in newborn neurons. Using adult male rats, we found that: (i) three days of voluntary physical exercise can definitively influence the morpho-functional maturation process of newborn granule neurons when applied very early during their development; (ii) a significant percentage of new neurons show more mature morphological characteristics far from the end of exercise protocol; (iii) the long-term morphological effects result in enhanced synaptic plasticity. Present findings demonstrate that the morpho-functional changes induced by exercise on very immature adult-generated neurons are permanent, affecting the neuron maturation and integration in hippocampal circuitry. Our data contribute to underpinning the beneficial potential of physical activity on brain health, also performed for short times.