bluuebunny/crossref_metadata_2025 huggingface dataset:
What Mechanisms Do Financial Marketization and China’s Fiscal Decentralization Have on Regional Energy Intensity? Evidence Based on Spatial Spillover and Panel Threshold Effects Perspectives
Authors: Pan Junbai , Lv Kun , Yu Shurong , Fu Dian
Published: May 2022

Energy efficiency and energy intensity are gradually gaining attention, and it is now an important proposition to reconcile financial marketization, fiscal decentralization, and regional energy intensity. Using Chinese mainland provincial panel data (except Tibet) from 2007 to 2019, this study applied the dynamic panel system generalized method of moments model, the spatial Durbin model, and the panel threshold model to investigate the mechanisms of financial marketization and fiscal decentralization on regional energy intensity. The study found that financial marketization can play a significant role in suppressing regional energy intensity, while fiscal decentralization promotes energy intensity. Meanwhile, financial marketization in one province can have a negative spatial transmission effect on energy intensity in other provinces, while fiscal decentralization in one province has a negative spatial spillover effect on energy intensity in other provinces. Based on the analysis of the moderating and threshold effects, financial marketization not only moderates the negative externality of fiscal decentralization, making it inhibit energy intensity in the opposite direction, but also gradually increases the moderating effect on fiscal decentralization as the degree of financial marketization increases, showing a nonlinear inhibiting effect on regional energy intensity.
Development and Validation of Earthquake Fire Response Simulation Protocol for Korean College Students in Health Programs
Authors: Jung Hyun-Ok , Han Seung-Woo
Published: May 2022

The purpose of this study is to evaluate the adequacy of the developed protocol by verifying the validity of the expert group for the earthquake and fire response simulation protocol. A protocol development team consisting of one emergency rescue professor, one counseling psychology professor, three paramedics, and one firefighter developed the study’s protocols to promote the core response and capabilities required at an earthquake fire site. We checked the content validity for the appropriateness of the contextual connection for each stage for the protocol. We also created an evaluation checklist to measure the items for each stage. The protocol developed in this study consists of earthquake response, fire response, evacuation, and fire suppression. We set the situation for each stage and composed learner activities and learning performance goals. The earthquake response stage included (1) shout “it’s an earthquake,” (2) protect yourself, (3) turn off electricity and gas, and (4) evacuate to a safe place. In the fire response stage, (1) shout “fire,” (2) press the emergency bell and call 119, (3) close the door of a dangerous place where fire can spread, and (4) evacuate to a safe place. In the evacuation stage, (1) open the emergency exit, (2) cover your nose and mouth, (3) lower your posture, and (4) evacuate quickly in one direction. Lastly, in the firefighting stage, (1) pull out the safety pin, (2) hold the nozzle and face the fire, (3) grab the handle, and (4) spray the powder evenly. The protocol contributes to the development of systematic and elaborate simulation education materials in the future. Furthermore, it provides basic data for future disaster simulation operation and protocol development through continuous training and practical exercises.
Implementation of Mental Health Centres Pilots in Poland since 2018: A Chance to Move towards Community-Based Mental Health Services
Authors: Sagan Anna , Kowalska-Bobko Iwona , Biechowska Daria , Rogala Maciej , Gałązka-Sobotka Małgorzata
Published: May 2022

Provision of mental health care in Poland has long been characterised by an overreliance on psychiatric hospitals and the underdevelopment of community care. The introduction of the first National Mental Health Protection Programme for 2011–2015, with the explicit goal to base provision of mental care on the community mental health centres, failed to achieve any tangible results. The ensuing critique led to the launch of the second National Mental Health Protection Programme for 2017–2022 and the establishment, from mid-2018 onwards, of 41 (33 in operation) mental health centres across Poland. These will be piloted until the end of 2022 but have already shown positive results in terms of access to non-stationary care and a small fall in hospitalisations. They have also performed well during the COVID-19 pandemic, allowing for a quick reorganization of care and continued provision of mental health services. Some of the key innovations of the new model include the introduction of recovery assistants (a new profession) and mental health coordinators (a new role); liaison with social assistance services; and a shift to budget financing. The key obstacles to the national rollout of mental health centres are the low financing of mental health care in Poland, which is among the lowest in Europe, and acute workforce shortages.
Gender, Age, Family and Territorial Features of Dietary and Physical Activity Patterns in Russian Youths
Authors: Kotova Marina B. , Maksimov Sergey A. , Drapkina Oksana M.
Published: May 2022

Objective: Identifying dietary and physical activity (PA) patterns in Russian youths and examining their dependence on gender, age, family characteristics and area of residence features. The research involved 783 school students 10–17 years of age and their parents living in the cities of Moscow and Murmansk. Using the principal component analysis, four integral indices were identified that characterized the habits and dietary patterns, PA and lifestyle. Boys, compared with girls, were more likely to consume unhealthy foods but less likely to practice malnutrition. Within the age ranges of 13–15 years old and 16–17 years old, the proportions of school students with a poor sleep pattern and low PA were higher than in children 10–12 years of age. In smoking families, children were less likely to consume healthy foods and more likely to eat unhealthy foods. In Murmansk school students, compared with their Moscow peers, a reduction in both sleep time and PA was observed less often. Our study demonstrated that the most significant factors of a balanced and healthy diet, rational daily routine and lifestyle in school students were their gender and age characteristics, as well as some contextual factors.
Cereal and Juice, Lead and Arsenic, Our Children at Risk: A Call for the FDA to Re-Evaluate the Allowable Limits of Lead and Arsenic That Children May Ingest
Authors: Neuwirth Lorenz S. , Cabañas Ericka , Cadet Patrick , Zhu Wei , Markowitz Morri E.
Published: May 2022

Eliminating heavy metal contamination of foods is a goal yet to be achieved in the U.S. In recent months, efforts have been underway to have the Food and Drug Administration (FDA) re-evaluate the permissible limits of lead (Pb) and arsenic (As) allowable in cereals and juices aimed for consumption by children. This report discusses the recent scientific literature that support proposed revisions in these limits. It presents proactive suggestions for the FDA to consider in its response to concerns of ongoing Pb and As exposures in food and drinks. While more scientific studies are needed to better define ‘safe’ levels of Pb and As exposures and ingestion of these elements in general are neurotoxic, the higher sensitivity of children to these toxic elements makes it imperative that the FDA adjust standards to be most protective of infants, toddlers, and children.
Anatomical Classification for Plantaris Tendon Insertion and Its Clinical Implications: A Cadaveric Study
Authors: Park Jeong-Hyun , Cho Jaeho , Kim Digud , Kwon Hyung-Wook , Lee Mijeong , Choi Yu-Jin , Yoon Kwan Hyun , Park Kwang-Rak
Published: May 2022

The purposes of this study were to ascertain the morphological characteristics of a plantaris tendon (PT) insertion using a larger-scale dissection of Korean cadavers and to classify the types of PT insertion related to the calcaneal tendon (CT). A total of 108 feet from adult formalin-fixed cadavers (34 males, 20 females) were dissected. The morphological characteristics and measurements of the PT insertion were evaluated. Five types of PT insertion were classified, wherein the most common type was Type 1 (39 feet, 63.1%). Type 2 and Type 3 were similar, with 16 feet (14.8%) and 15 feet (13.9%), respectively. Type 4 (6 feet, 5.6%) was the rarest type, and Type 5 had 25 feet (23.1%). The case of an absent PT was noted in 7 feet (6.5%). In the proximal portion, the tendon had a thick and narrow shape, became thin and wide in the middle portion, and then changed to thick and narrow again just before the insertion into the calcaneal tuberosity. This study confirmed the five types according to the location of the PT and the area of its insertion-related CT. The morphology of the PT insertion may be anatomically likely to influence the occurrence of tendinopathy in the CT.
Content, Structure and Delivery Characteristics of Yoga Interventions for the Management of Osteoarthritis: A Systematic Review Protocol
Authors: Biswas Isha , Lewis Sarah , Chattopadhyay Kaushik
Published: May 2022

The global burden of osteoarthritis among adults is rising. Yoga might be a potential solution for the management of osteoarthritis. This systematic review aims to synthesise the content, structure and delivery characteristics of effective yoga interventions for the management of osteoarthritis. The JBI methodology for systematic reviews of effectiveness and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines will be followed. Randomised controlled trials (RCTs) assessing the effectiveness of yoga interventions for the management of osteoarthritis in adults will be included in this review. We aim to search the following databases to find published and unpublished studies: MEDLINE, EMBASE, CINAHL, PsycInfo, SPORTDiscus, AMED, Web of Science, CENTRAL, TRIP, AYUSH Research Portal, ABIM, CAM-QUEST, PeDro, OpenGrey, EthOS, ProQuest Dissertations and Theses and DART-Europe-e-theses portal. No date or language restrictions will be applied. A narrative synthesis will be conducted with the help of tables. A meta-regression will be conducted to explore the statistical evidence for which the components (content, structure and delivery characteristics) of yoga interventions are effective.
Low-Level Radon Activity Concentration—A MetroRADON International Intercomparison
Authors: Otahal Petr P. S. , Fialova Eliska , Vosahlik Josef , Wiedner Hannah , Grossi Claudia , Vargas Arturo , Michielsen Nathalie , Turtiainen Tuukka , Luca Aurelian , Wołoszczuk Katarzyna , Beck Thomas R.
Published: May 2022

An international comparison of continuous monitors measuring radon activity concentration was performed to validate the traceability of the European radon calibration facilities. It was carried out by comparing the secondary standards used by these previous facilities, ranging from 100 Bq·m−3 to 300 Bq·m−3. Secondary standards were individually compared to a secondary reference device previously calibrated in a reference radon atmosphere traceable to a primary standard. The intercomparison was organized by the National Institute for Nuclear, Chemical, and Biological Protection (SUJCHBO) in the period from October 2019 to April 2020 within the European Metrology Program for Innovation and Research (EMPIR), JRP-Contract 16ENV10 MetroRADON. Eight European laboratories participated in this study. The results of the experiment are presented and discussed.
Effects of Core Training in Physical Fitness of Youth Karate Athletes: A Controlled Study Design
Authors: Kabadayı Menderes , Karadeniz Soner , Yılmaz Ali Kerim , Karaduman Emre , Bostancı Özgür , Akyildiz Zeki , Clemente Filipe Manuel , Silva Ana Filipa
Published: May 2022

This study aimed to analyse the impact of an 8-week core strength training (CST) programme in youth karate practitioners on core endurance, agility, flexibility, sprinting, jumping, and kick performance. This study followed a randomized parallel design. Twenty-nine participants (age: 12.86 ± 0.81 years old; height: 152.55 ± 10.37 cm; weight: 42.93 ± 8.85 kg) were allocated to a CST programme (n = 16) performed thrice weekly or to a control group (n = 13) only performing the sport-specific (karate) training. Participants were assessed three times (baseline, mid and post-intervention) for the following tests: (i) flexor endurance test (FET); (ii) back extensor test (BET); (iii) lateral musculature test (LMT); (iv) flexibility; (v) chance of direction (COD); (vi) countermovement jump (CMJ); (vii) back muscle strength (BMS); (viii) horizontal jump (LJ); (ix) sprint test; and (x) karate kick test (KKT). Between-group analysis revealed significant advantages for the CST group on the FET (p < 0.001), BET (p < 0.001), LMT (p < 0.001), 20 m sprint (p = 0.021) and KKT for right (p < 0.006) and left (p < 0.020) legs. No significant differences were found between groups in the remaining physical fitness variables (p > 0.05). The within-group changes revealed significant improvements in the CST group at flexibility (p = 0.002), COD (p < 0.001), CMJ (p < 0.001), BMS (p < 0.002), 20 m sprint (p = 0.033), and KKT (p < 0.001). In addition, within-group changes in the control group were also significant in flexibility (p = 0.024) and right kick (p < 0.042). We conclude that the CST programme improves core endurance and karate kick performance; however, it is not effective enough for other physical performance parameters in KR practitioners.
Cross-Sectional Associations between Living and Built Environments and Depression Symptoms among Chinese Older Adults
Authors: Hou Fangfang , Han Xiao , Wang Qiong , Zhou Shuai , Zhang Jingya , Shen Guodong , Zhang Yan
Published: May 2022

In this study, we explored the cross-sectional associations between living and built environments and depression among older Chinese adults. Data from 5822 participants were obtained. Depression symptoms were evaluated through the use of the Patient Health Questionnaire (PHQ-9), with a score higher than 4 categorized as having depression symptoms. The living environment was assessed by asking about dust in the environment and barrier-free facilities. We considered the presence of amenities within a 10 min walking distance and the proportion of green space within an 800 m distance from participants’ dwellings to reflect the built environment. Data were analyzed by multilevel logistic regression. Participants living in a non-dusty environment with proximity to green space had a lower risk of depression (non-dusty environment: OR = 0.784, 95% CI = 0.642, 0.956; green space: OR = 0.834, 95% CI = 0.697, 0.998). However, having no access to barrier-free facilities and hospital proximity increased the depression risk (barrier-free facilities: OR = 1.253, 95% CI = 1.078, 1.457; hospital: OR = 1.318, 95% CI = 1.104, 1.574). Dusty environments, access to barrier-free facilities and proximity to hospitals and green spaces were associated with depression symptoms among older Chinese adults.
Psychometric Properties for Multidimensional Cognitive Load Scale in an E-Learning Environment
Authors: Choi Younyoung , Lee Hyunwoo
Published: May 2022

(1) Background: A learner’s cognitive load in a learning system should be effectively addressed to provide optimal learning processing because the cognitive load explains individual learning differences. However, little empirical research has been conducted into the validation of a cognitive load measurement tool (cognitive load scale, i.e., CLS) suited to online learning systems within higher education. The purpose of this study was to evaluate the psychometric properties of the CLS in an online learning system within higher education through the framework suggested by the Standards for Educational and Psychological Testing. (2) Methods: Data from 800 learners were collected from a cyber-university in South Korea. The age of students ranged from 20 to 64. The CLS was developed, including three components: extraneous cognitive load, intrinsic cognitive load, and germane cognitive load. Then, psychometric properties of the CLS were evaluated including reliability and validity. Evidence relating to content validity, construct validity, and criterion validity were collected. The response pattern of each item was evaluated on the basis of item response theory (IRT). Cronbach’s α was computed for reliability. (3) Results: The CLS presented high internal consistency. A three-factor model with extraneous cognitive load, intrinsic cognitive load, and germane cognitive load was suggested by exploratory and confirmatory factor analysis. This three-factor model is consistent with the previous research into the cognitive load in an offline learning environment. Higher levels of the extraneous cognitive load and intrinsic cognitive load were related to lower levels of academic achievement in an online learning environment, but the germane cognitive load was not significantly positively associated with midterm exam scores, though it was significantly related to the final exam scores. IRT analysis showed that the item-fit statistics for all items were acceptable. Lastly, the measurement invariance was examined through differential item functioning analysis (DIF), with the results suggesting that the items did not contain measurement variance in terms of gender. (4) Conclusions: This validation study of the CLS in an online learning environment within higher education assesses psychometric properties and suggests that the CLS is valid and reliable with a three-factor model. There is a need for an evaluation tool to take into account the cognitive load among learners in online learning system because the characteristics of learners within higher education were varied. This CLS will help instructional/curriculum designers and educational instructors to provide more effective instructions and identify individual learning differences in an online learning environment within higher education.
The Structure and Function of Next-Generation Gingival Graft Substitutes—A Perspective on Multilayer Electrospun Constructs with Consideration of Vascularization
Authors: Webb Brian C. W. , Glogauer Michael , Santerre J. Paul
Published: May 2022

There is a shortage of suitable tissue-engineered solutions for gingival recession, a soft tissue defect of the oral cavity. Autologous tissue grafts lead to an increase in morbidity due to complications at the donor site. Although material substitutes are available on the market, their development is early, and work to produce more functional material substitutes is underway. The latter materials along with newly conceived tissue-engineered substitutes must maintain volumetric form over time and have advantageous mechanical and biological characteristics facilitating the regeneration of functional gingival tissue. This review conveys a comprehensive and timely perspective to provide insight towards future work in the field, by linking the structure (specifically multilayered systems) and function of electrospun material-based approaches for gingival tissue engineering and regeneration. Electrospun material composites are reviewed alongside existing commercial material substitutes’, looking at current advantages and disadvantages. The importance of implementing physiologically relevant degradation profiles and mechanical properties into the design of material substitutes is presented and discussed. Further, given that the broader tissue engineering field has moved towards the use of pre-seeded scaffolds, a review of promising cell options, for generating tissue-engineered autologous gingival grafts from electrospun scaffolds is presented and their potential utility and limitations are discussed.
Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue
Authors: Cohn Whitaker , Zhu Chunni , Campagna Jesus , Bilousova Tina , Spilman Patricia , Teter Bruce , Li Feng , Guo Rong , Elashoff David , Cole Greg M. , Avidan Alon , Faull Kym Francis , Whitelegge Julian , Wong David T. W. , John Varghese
Published: May 2022

Fatigue and other deleterious mood alterations resulting from prolonged efforts such as a long work shift can lead to a decrease in vigilance and cognitive performance, increasing the likelihood of errors during the execution of attention-demanding activities such as piloting an aircraft or performing medical procedures. Thus, a method to rapidly and objectively assess the risk for such cognitive fatigue would be of value. The objective of the study was the identification in saliva-borne exosomes of molecular signals associated with changes in mood and fatigue that may increase the risk of reduced cognitive performance. Using integrated multiomics analysis of exosomes from the saliva of medical residents before and after a 12 h work shift, we observed changes in the abundances of several proteins and miRNAs that were associated with various mood states, and specifically fatigue, as determined by a Profile of Mood States questionnaire. The findings herein point to a promising protein biomarker, phosphoglycerate kinase 1 (PGK1), that was associated with fatigue and displayed changes in abundance in saliva, and we suggest a possible biological mechanism whereby the expression of the PGK1 gene is regulated by miR3185 in response to fatigue. Overall, these data suggest that multiomics analysis of salivary exosomes has merit for identifying novel biomarkers associated with changes in mood states and fatigue. The promising biomarker protein presents an opportunity for the development of a rapid saliva-based test for the assessment of these changes.
Fluorescence Lifetime Phasor Analysis of the Decamer–Dimer Equilibrium of Human Peroxiredoxin 1
Authors: Villar Sebastián F. , Dalla-Rizza Joaquín , Möller Matías N. , Ferrer-Sueta Gerardo , Malacrida Leonel , Jameson David M. , Denicola Ana
Published: May 2022

Protein self-assembly is a common feature in biology and is often required for a myriad of fundamental processes, such as enzyme activity, signal transduction, and transport of solutes across membranes, among others. There are several techniques to find and assess homo-oligomer formation in proteins. Naturally, all these methods have their limitations, meaning that at least two or more different approaches are needed to characterize a case study. Herein, we present a new method to study protein associations using intrinsic fluorescence lifetime with phasors. In this case, the method is applied to determine the equilibrium dissociation constant (KD) of human peroxiredoxin 1 (hPrx1), an efficient cysteine-dependent peroxidase, that has a quaternary structure comprised of five head-to-tail homodimers non-covalently arranged in a decamer. The hPrx1 oligomeric state not only affects its activity but also its association with other proteins. The excited state lifetime of hPrx1 has distinct values at high and low concentrations, suggesting the presence of two different species. Phasor analysis of hPrx1 emission lifetime allowed for the identification and quantification of hPrx1 decamers, dimers, and their mixture at diverse protein concentrations. Using phasor algebra, we calculated the fraction of hPrx1 decamers at different concentrations and obtained KD (1.1 × 10−24 M4) and C0.5 (1.36 μM) values for the decamer–dimer equilibrium. The results were validated and compared with size exclusion chromatography. In addition, spectral phasors provided similar results despite the small differences in emission spectra as a function of hPrx1 concentration. The phasor approach was shown to be a highly sensitive and quantitative method to assess protein oligomerization and an attractive addition to the biophysicist’s toolkit.
Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis
Authors: Belgacemi Randa , Danopoulos Soula , Deutsch Gail , Glass Ian , Dormoy Valérian , Bellusci Saverio , Al Alam Denise
Published: May 2022

The Hedgehog (HH) signaling pathway plays an essential role in mouse lung development. We hypothesize that the HH pathway is necessary for branching during human lung development and is impaired in pulmonary hypoplasia. Single-cell, bulk RNA-sequencing data, and human fetal lung tissues were analyzed to determine the spatiotemporal localization of HH pathway actors. Distal human lung segments were cultured in an air-liquid interface and treated with an SHH inhibitor (5E1) to determine the effect of HH inhibition on human lung branching, epithelial-mesenchymal markers, and associated signaling pathways in vitro. Our results showed an early and regulated expression of HH pathway components during human lung development. Inhibiting HH signaling caused a reduction in branching during development and dysregulated epithelial (SOX2, SOX9) and mesenchymal (ACTA2) progenitor markers. FGF and Wnt pathways were also disrupted upon HH inhibition. Finally, we demonstrated that HH signaling elements were downregulated in lung tissues of patients with a congenital diaphragmatic hernia (CDH). In this study, we show for the first time that HH signaling inhibition alters important genes and proteins required for proper branching of the human developing lung. Understanding the role of the HH pathway on human lung development could lead to the identification of novel therapeutic targets for childhood pulmonary diseases.
Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
Authors: Son So-Eun , Koh Jung-Min , Im Dong-Soon
Published: May 2022

Epidemiological and clinical studies have suggested that intake of n-3 polyunsaturated fatty acids (PUFA) reduces the incidence of allergic airway diseases and improves pulmonary function in patients with allergic asthma. However, the pharmacological targets of PUFA have not been elucidated upon. We investigated whether free fatty acid receptor 4 (FFA4, also known as GPR120) is a molecular target for beneficial PUFA in asthma therapy. In an ovalbumin (OVA)-induced allergic asthma model, compound A (a selective agonist of FFA4) was administrated before OVA sensitization or OVA challenge in FFA4 wild-type (WT) and knock-out (KO) mice. Compound A treatment of RBL-2H3 cells suppressed mast cell degranulation in vitro in a concentration-dependent manner. Administration of compound A suppressed in vivo allergic characteristics in bronchoalveolar lavage fluid (BALF) and lungs, such as inflammatory cytokine levels and eosinophil accumulation in BALF, inflammation and mucin secretion in the lungs. Compound A-induced suppression was not only observed in mice treated with compound A before OVA challenge, but in mice treated before OVA sensitization as well, implying that compound A acts on mast cells as well as dendritic cells. Furthermore, this suppression by compound A was only observed in FFA4-WT mice and was absent in FFA4-KO mice, implying that compound A action is mediated through FFA4. Activation of FFA4 may be a therapeutic target of PUFA in allergic asthma by suppressing the activation of dendritic cells and mast cells, suggesting that highly potent specific agonists of FFA4 could be a novel therapy for allergic asthma.
Granzymes—Their Role in Colorectal Cancer
Authors: Pączek Sara , Łukaszewicz-Zając Marta , Mroczko Barbara
Published: May 2022

Colorectal cancer (CRC) is among the most common malignancies worldwide. CRC is considered a heterogeneous disease due to various clinical symptoms, biological behaviours, and a variety of mutations. A number of studies demonstrate that as many as 50% of CRC patients have distant metastases at the time of diagnosis. However, despite the fact that social and medical awareness of CRC has increased in recent years and screening programmes have expanded, there is still an urgent need to find new diagnostic tools for early detection of CRC. The effectiveness of the currently used classical tumour markers in CRC diagnostics is very limited. Therefore, new proteins that play an important role in the formation and progression of CRC are being sought. A number of recent studies show the potential significance of granzymes (GZMs) in carcinogenesis. These proteins are released by cytotoxic lymphocytes, which protect the body against viral infection as well specific signalling pathways that ultimately lead to cell death. Some studies suggest a link between GZMs, particularly the expression of Granzyme A, and inflammation. This paper summarises the role of GZMs in CRC pathogenesis through their involvement in the inflammatory process. Therefore, it seems that GZMs could become the focus of research into new CRC biomarkers.
Solvation, Cancer Cell Photoinactivation and the Interaction of Chlorin Photosensitizers with a Potential Passive Carrier Non-Ionic Surfactant Tween 80
Authors: Kustov Andrey V. , Morshnev Philipp K. , Kukushkina Natal’ya V. , Smirnova Nataliya L. , Berezin Dmitry B. , Karimov Dmitry R. , Shukhto Olga V. , Kustova Tatyana V. , Belykh Dmitry V. , Mal’shakova Marina V. , Zorin Vladimir P. , Zorina Tatyana E.
Published: May 2022

Cancer and drug-resistant superinfections are common and serious problems afflicting millions worldwide. Photodynamic therapy (PDT) is a successful and clinically approved modality used for the management of many neoplastic and nonmalignant diseases. The combination of the light-activated molecules, so-called photosensitizers (PSs), with an appropriate carrier, is proved to enhance PDT efficacy both in vitro and in vivo. In this paper, we focus on the solvation of several potential chlorin PSs in the 1-octanol/phosphate saline buffer biphasic system, their interaction with non-ionic surfactant Tween 80 and photoinactivation of cancer cells. The chlorin conjugates containing d-galactose and l-arginine fragments are found to have a much stronger affinity towards a lipid-like environment compared to ionic chlorins and form molecular complexes with Tween 80 micelles in water with two modes of binding. The charged macrocyclic PSs are located in the periphery of surfactant micelles near hydrophilic head groups, whereas the d-galactose and l-arginine conjugates are deeper incorporated into the micelle structure occupying positions around the first carbon atoms of the hydrophobic surfactant residue. Our results indicate that both PSs have a pronounced affinity toward the lipid-like environment, leading to their preferential binding to low-density lipoproteins. This and the conjugation of chlorin e6 with the tumor-targeting molecules are found to enhance their accumulation in cancer cells and PDT efficacy.
Profiling of Non-Coding Regulators and Their Targets in Epicardial Fat from Patients with Coronary Artery Disease
Authors: Flinn Brendin , Adams Christopher , Chowdhury Nepal , Gress Todd , Santanam Nalini
Published: May 2022

Epicardial fat is a continuously growing target of investigation in cardiovascular diseases due to both its anatomical proximity to the heart and coronary circulation and its unique physiology among adipose depots. Previous reports have demonstrated that epicardial fat plays key roles in coronary artery disease, but the non-coding RNA and transcriptomic alterations of epicardial fat in coronary artery disease have not been investigated thoroughly. Micro- and lncRNA microarrays followed by GO-KEGG functional enrichment analysis demonstrated sex-dependent unique mi/lncRNAs altered in human epicardial fat in comparison to subcutaneous fat in both patients with and without coronary artery disease (IRB approved). Among the 14 differentially expressed microRNAs in epicardial fat between patients with and without coronary artery disease, the hsa-miR-320 family was the most highly represented. IPW lncRNA interacted with three of these differentially expressed miRNAs. Next-generation sequencing and pathway enrichment analysis identified six unique mRNAs–miRNA pairs. Pathway enrichment identified inflammation, adipogenesis, and cardiomyocyte apoptosis as the most represented functions altered by the mi/lncRNAs and atherosclerosis and myocardial infarction among the highest cardiovascular pathologies associated with them. Overall, the epicardial fat in patients with coronary artery disease has a unique mi/lncRNA profile which is sex-dependent and has potential implications for regulating cardiac function.
Editorial to Special Issue “Sleep Apnea and Intermittent Hypoxia 2.0”
Authors: Takasawa Shin
Published: May 2022

Sleep apnea syndrome (SAS) is the most common form of sleep-disordered breathing and is associated with many adverse health consequences, including increased overall mortality risk [...]
The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity
Authors: DeVera Christopher , Dixon Jendayi , Chrenek Micah A. , Baba Kenkichi , Le Yun Z. , Iuvone P. Michael , Tosini Gianluca
Published: May 2022

The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments (POS) is under circadian control and believed that this process involves interactions from the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE. Thereby, the aim of this study was to determine whether the clock in the retina or RPE controls the diurnal phagocytic peak and whether disruption of the circadian clock in the RPE would affect cellular function and the viability during aging. To that, we generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then, using electroretinography, spectral domain-optical coherence tomography, and optomotor response of visual function we determined the effect of Bmal1 removal in young (6 months) and old (18 months) mice. RPE morphology and lipofuscin accumulation was determined in young and old mice. Our data shows that the clock in the RPE, rather than the retina clock, controls the diurnal phagocytic peak. Surprisingly, absence of a functional RPE clock and phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the circadian clock in the RPE controls the daily peak of phagocytic activity. However, the absence of the clock in the RPE does not result in deterioration of photoreceptors or the RPE during aging.
Design of Artificial Enzymes Bearing Several Active Centers: New Trends, Opportunities and Problems
Authors: Carballares Diego , Morellon-Sterling Roberto , Fernandez-Lafuente Roberto
Published: May 2022

Harnessing enzymes which possess several catalytic activities is a topic where intense research has been carried out, mainly coupled with the development of cascade reactions. This review tries to cover the different possibilities to reach this goal: enzymes with promiscuous activities, fusion enzymes, enzymes + metal catalysts (including metal nanoparticles or site-directed attached organometallic catalyst), enzymes bearing non-canonical amino acids + metal catalysts, design of enzymes bearing a second biological but artificial active center (plurizymes) by coupling enzyme modelling and directed mutagenesis and plurizymes that have been site directed modified in both or in just one active center with an irreversible inhibitor attached to an organometallic catalyst. Some examples of cascade reactions catalyzed by the enzymes bearing several catalytic activities are also described. Finally, some foreseen problems of the use of these multi-activity enzymes are described (mainly related to the balance of the catalytic activities, necessary in many instances, or the different operational stabilities of the different catalytic activities). The design of new multi-activity enzymes (e.g., plurizymes or modified plurizymes) seems to be a topic with unarguable interest, as this may link biological and non-biological activities to establish new combo-catalysis routes.
Role of Leptin and Adiponectin in Endometrial Cancer
Authors: Słabuszewska-Jóźwiak Aneta , Lukaszuk Aron , Janicka-Kośnik Marta , Wdowiak Artur , Jakiel Grzegorz
Published: May 2022

Endometrial cancer is the most common malignancy of the female genital tract. Obesity is a strong risk factor for endometrial cancer. Adipose tissue is an active endocrine organ that synthesizes biologically active cytokine peptides, called adipokines. Adiponectin and leptin are the main cytokines of adipose tissue, which may influence the development of metabolic diseases and carcinogenesis. In this scenario, we describe the role of leptin and adiponectin in the development of endometrial cancer. A better understanding of the signalling pathway of these cytokines in endometrial cancerogenesis will provide an opportunity for effective target therapy and may be usable in fertility-sparing treatment. In the future, clinical trials focusing on adipokines, molecular biology, and genetics of the tumour will be needed.
Anti-Fungal Analysis of Bacillus subtilis DL76 on Conidiation, Appressorium Formation, Growth, Multiple Stress Response, and Pathogenicity in Magnaporthe oryzae
Authors: Kgosi Veronica Tshogofatso , Tingting Bao , Ying Zhao , Liu Hongxia
Published: May 2022

In recent years, biological control has gained more attention as a promising method to combat plant disease. Such severe diseases cited include rice blasts caused by Magnaporthe oryzae. However, more effective microbial strains with strong adaptability still need to be identified. Therefore, we sought to assess the conidia germination, and formation of appressorium of DL76 in Magnaporthe oryzae. Besides, we also aimed at understanding the growth, multiple stress response and pathogenicity in Magnaporthe oryzae. We isolated Bacillus subtilis DL76 from a rice farm, which observed a strong antimicrobial effect on M. oryzae. The sterilized culture filtrate of DL76 inhibited the growth of M. oryzae, which motivated us to deduce the influence of DL76 on the pathogenicity of M. oryzae. We screened the effect of Bacillus subtilis DL76 on M. oryzae guy11. It demonstrated that sterilized culture filtrate (1 × 107 CFU/mL) of DL76 can delay and even suppress the germination of conidia and (1 × 107 and 1 × 106 CFU/mL) prevent the formation of appressorium in vitro and in vivo. DL76 became hypersensitive to osmotic, oxidative, and cell wall degrading agents. In addition, the relative transcript levels of stress-responsive genes oxidative and osmotic were down-regulated by DL76 except for sod1, cat1, and cat2. In vivo assessment of the antifungal activity of Bacillus subtilis using conidia suspension of DL76 reduced the incidence and severity of rice blast. Conclusively, our results show that DL76 is essential for controlling rice blast by inhibiting conidiation, growth, multiple stress tolerance, and pathogenicity in M. oryzae.
Physiological Role of ATPase for GABAA Receptor Resensitization
Authors: Menzikov Sergey A. , Zaichenko Danila M. , Moskovtsev Aleksey A. , Morozov Sergey G. , Kubatiev Aslan A.
Published: May 2022

γ-Aminobutyric acid type A receptors (GABAARs) mediate primarily inhibitory synaptic transmission in the central nervous system. Following fast-paced activation, which provides the selective flow of mainly chloride (Cl−) and less bicarbonate (HCO3−) ions via the pore, these receptors undergo desensitization that is paradoxically prevented by the process of their recovery, referred to as resensitization. To clarify the mechanism of resensitization, we used the cortical synaptoneurosomes from the rat brain and HEK 293FT cells. Here, we describe the effect of γ-phosphate analogues (γPAs) that mimic various states of ATP hydrolysis on GABAAR-mediated Cl− and HCO3− fluxes in response to the first and repeated application of the agonist. We found that depending on the presence of bicarbonate, opened and desensitized states of the wild or chimeric GABAARs had different sensitivities to γPAs. This study presents the evidence that recovery of neuronal Cl− and HCO3− concentrations after desensitization is accompanied by a change in the intracellular ATP concentration via ATPase performance. The transition between the desensitization and resensitization states was linked to changes in both conformation and phosphorylation. In addition, the chimeric β3 isoform did not exhibit the desensitization of the GABAAR-mediated Cl− influx but only the resensitization. These observations lend a new physiological significance to the β3 subunit in the manifestation of GABAAR resensitization.
Oral Administration of Omega-3 Fatty Acids Attenuates Lung Injury Caused by PM2.5 Respiratory Inhalation Simply and Feasibly In Vivo
Authors: Li Juan , Mao Meiru , Li Jiacheng , Chen Ziteng , Ji Ying , Kong Jianglong , Wang Zhijie , Zhang Jiaxin , Wang Yujiao , Liang Wei , Liang Haojun , Lv Linwen , Liu Qiuyang , Yan Ruyu , Yuan Hui , Chen Kui , Chang Yanan , Chen Guogang , Xing Gengmei
Published: May 2022

For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.
The Synthesis Methodology and Characterization of Nanogold-Coated Fe3O4 Magnetic Nanoparticles
Authors: Kędzierska Magdalena , Drabczyk Anna , Jamroży Mateusz , Kudłacik-Kramarczyk Sonia , Głąb Magdalena , Tyliszczak Bożena , Bańkosz Wojciech , Potemski Piotr
Published: May 2022

Core-shell nanostructures are widely used in many fields, including medicine and the related areas. An example of such structures are nanogold-shelled Fe3O4 magnetic nanoparticles. Systems consisting of a magnetic core and a shell made from nanogold show unique optical and magnetic properties. Thus, it is essential to develop the methodology of their preparation. Here, we report the synthesis methodology of Fe3O4@Au developed so as to limit their agglomeration and increase their stability. For this purpose, the impact of the reaction environment was verified. The properties of the particles were characterized via UV-Vis spectrophotometry, dynamic light scattering (DLS), X-ray diffraction (XRD), and Scanning Electron Microscopy-Energy Dispersive X-ray analysis (SEM-EDS technique). Moreover, biological investigations, including determining the cytotoxicity of the particles towards murine fibroblasts and the pro-inflammatory activity were also performed. It was demonstrated that the application of an oil and water reaction environment leads to the preparation of the particles with lower polydispersity, whose agglomerates’ disintegration is 24 times faster than the disintegration of nanoparticle agglomerates formed as a result of the reaction performed in a water environment. Importantly, developed Fe3O4@Au nanoparticles showed no pro-inflammatory activity regardless of their concentration and the reaction environment applied during their synthesis and the viability of cell lines incubated for 24 h with the particle suspensions was at least 92.88%. Thus, the developed synthesis methodology of the particles as well as performed investigations confirmed a great application potential of developed materials for biomedical purposes.
Environmental and Production Aspects of Using Fertilizers Based on Waste Elemental Sulfur and Organic Materials
Authors: Lisowska Aneta , Filipek-Mazur Barbara , Komorowska Monika , Niemiec Marcin , Bar-Michalczyk Dominika , Kuboń Maciej , Tabor Sylwester , Gródek-Szostak Zofia , Szeląg-Sikora Anna , Sikora Jakub , Kocira Sławomir , Wasąg Zbigniew
Published: May 2022

Crop fertilization with sulfur is an important part of agricultural practices, as is the systematic increase in soil organic matter content. Materials of waste origin constitute a source of plant-available sulfur, as well as soil organic matter. The study was to verify the hypothesis assuming that combining waste sulfur pulp and its mixtures with organic materials enables simultaneous soil enrichment with readily available sulfur and organic matter. A 240-day incubation experiment was conducted, on two soils: very light and heavy; with two sulfur doses applied to each soil (20 and 40 mg S/kg d.m. for very light soil, and 30 and 60 mg S/kg d.m. for heavy soil). The sulfate sulfur content in the incubated soil material, treated with the addition of sulfur pulp and its mixtures with organic materials, increased significantly up to day 60 and then decreased. The application of these materials significantly increased the content of available sulfur and decreased the pH value of the incubated material. The effect of the introduced materials on dehydrogenase activity depended on soil granulometric composition (the impact of the applied materials on the activity of these enzymes in very light soil was small, and in heavy soil, their activity was usually limited by the presence of introduced materials). Application of the studied materials had little effect on the total organic carbon content in the incubated soil material (a significant change in the value of this parameter, in relation to the control soil, was recorded in some treatments of heavy soil).
Comparison of Melting Processes for WPC and the Resulting Differences in Thermal Damage, Emissions and Mechanics
Authors: Wiedl Sebastian , Karlinger Peter , Schemme Michael , List Manuela , Ruckdäschel Holger
Published: May 2022

The necessity for resource-efficient manufacturing technologies requires new developments within the field of plastic processing. Lightweight design using wood fibers as sustainable reinforcement for thermoplastics might be one solution. The processing of wood fibers requires special attention to the applied thermal load. Even at low processing temperatures, the influence of the dwell time, temperature and shear force is critical to ensure the structural integrity of fibers. Therefore, this article compares different compounding rates for polypropylene with wood fibers and highlights their effects on the olfactory, visual and mechanical properties of the injection-molded part. The study compares one-step processing, using an injection-molding compounder (IMC), with two-step processing, using a twin-scew-extruder (TSE), a heating/cooling mixer (HCM) and an internal mixer (IM) with subsequent injection molding. Although the highest fiber length was achieved by using the IMC, the best mechanical properties were achieved by the HCM and IM. The measured oxidation induction time and volatile organic compound content indicate that the lowest amount of thermal damage occurred when using the HCM and IM. The advantage of one-time melting was evened out by the dwell time. The reinforcement of thermoplastics by wood fibers depends more strongly on the structural integrity of the fibers compared to their length and homogeneity.