bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydro-Stratigraphic Conditions and Human Activity Leading to Development of a Sinkhole Cluster in a Mediterranean Water Ecosystem
Authors: Margiotta Stefano , Marini Gabriele , Fay Sergio , D’Onghia Francesco M. , Liso Isabella S. , Parise Mario , Pinna Maurizio
Published: August 2021

Salento Peninsula (Apulia, southern Italy) is characterised by many active sinkholes, which represent the main geological hazard. The stretch of coastline between the village of Casalabate and Le Cesine wildlife reserve is highly affected, with a system of dunes separating the low beach from extensive wetlands, which were subject to uncontrolled urban development after reclamation. The overall morphology is characterized by flat topography, whilst from a hydrogeological standpoint, the mixing of inland freshwater with advancing brackish water favours the higher aggressivity with respect to soluble rocks, and the development of enhanced dissolution (hyperkarst). The relict landscapes within the protected areas still allow for the recognition of actively occurring sinkholes, which cause damage to houses, the road network and infrastructures. In this article the case of Aquatina di Frigole is described, where in the last 15 years numerous sinkholes have formed, with the processes still in rapid evolution. Detailed surveys allow for to identification of the mechanisms of sinkhole formation (suffusion sinkholes), the deriving cluster, and the main hydrogeological links among the different water bodies in the area. Acquatina di Frigole provides an excellent natural laboratory to observe development and evolution of sinkholes, and their relationships with the stratigraphic and hydrogeological elements.
Occurrence, Distribution, and Ecological Risk Assessment of Antibiotics in Different Environmental Media in Anqing, Anhui Province, China
Authors: Chen Haiying , Zheng Wenfang , Shen Xiaoming , Zhang Fei , Zhou Xiaoping , Shen Jialin , Lu Ming
Published: August 2021

The widespread usage of antibiotics in human and animal medication has brought global concerns over environmental contamination of antibiotic residues. In this study, 16 kinds of antibiotics in different environmental media of water, sediments, and soils in Anqing city, Anhui province were determined by ultra-performance liquid chromatography tandem mass spectrometry. A total of fourteen kinds of antibiotics were detected in surface water, with a total concentration up to 479 ng·L−1, while six kinds of antibiotics were detected in sediment and soil with concentrations ranging from 15.1 to 108 μg·kg−1. Ciprofloxacin (12.8–99.5 ng·L−1) and tetracycline (17.2–225 μg·kg−1) antibiotics exhibited the highest concentration in water and soil, respectively. In spatial distribution, the total concentration of antibiotics in surface water from the highest to the lowest followed the order of urban area, mainstream of Wan River, suburbs, tributaries of Wan River, indicating that the level of antibiotic concentration in surface water is positively associated with the frequency of human activities. In addition, the antibiotic mass fraction in agriculture land and fishpond were found higher than that in other sampling sites. Moreover, the environmental risk assessment results showed that ciprofloxacin, erythromycin, ofloxacin, enrofloxacin and tetracycline might pose medium to high risks to algae and bacteria in aquatic ecosystem.
Effect of Summer Sunshine Exposure on Vitamin D Status in Young and Middle Age Poles: Is 30 ng/mL Vitamin D Cut-Off Really Suitable for the Polish Population?
Authors: Basińska-Lewandowska Magdalena , Lewiński Andrzej , Horzelski Wojciech , Skowrońska-Jóźwiak Elżbieta
Published: August 2021

Background: There is no consensus regarding vitamin sufficiency status with either 20 ng/mL or 30 ng/mL sufficiency cut-off. We assessed the effects of summer sunshine exposure on vitamin D status. Participants: We measured vitamin D concentrations, PTH, creatinine, and total calcium in 132 healthy subjects, age 29.36 ± 13.57 years, in spring and autumn. Results: There was an overall increase in vitamin D concentrations from spring to autumn from 18.1 ± 7.39 ng/mL to 24.58 ± 7.72 ng/mL, (p < 0.001), accompanied by a decrease in PTH from 44.4 ± 17.76 pg/mL to 36.6 ± 14.84 pg/mL, (p < 0.001). In spring, only 5.3% of individuals were vitamin D sufficient for a 30 ng/mL cut-off, increasing to 23.2% in autumn (p < 0.001). In contrast, when a 20 ng/mL cut-off was employed, vitamin D sufficiency was found in 34.1% in spring and 66.4% individuals in autumn, respectively, (p < 0.001). In multiple regression analysis, holiday leave was the only significant determinant of vitamin D increase (p < 0.001). Conclusions: Holiday leave is the strongest determinant of an increase in vitamin D. The majority of healthy individuals fail to reach a 30 ng/mL vitamin D cut-off after summer sunshine exposure. This raises the question, whether such a cut-off is indeed suitable for the Polish population.
Parental Factors Related to Adolescent Girls’ Suicide Attempts: A Cross-Sectional Study from 2015 to 2018
Authors: Lee Yeon-Jung , Lee Jin-Young , Kim Minjae
Published: August 2021

Adolescent suicide is a serious global health concern. Although familial transmission of suicidal behaviors has been identified in previous research, the effects of parental gender remain unknown. This study identified the influence of parental suicidal behaviors on suicide attempts among adolescent girls. We collected data through a cross-sectional, nationwide, population-based survey in South Korea and evaluated data from 890 adolescent girls (aged 12–18 years) who had attempted suicide and their parents. Hierarchical logistic regression was used to analyze the risk factors related to suicide attempts among adolescent girls. The final model indicated that mothers’ suicidal plans and attempts (OR = 6.39, OR = 12.38, respectively) were important risk factors for suicide attempts in adolescent girls. Future studies should identify specific methods for effective prevention and treatment through path analysis of the related factors affecting suicidal behavior of adolescents according to their parents’ gender.
Supportive Care and Unmet Needs in Upper Gastrointestinal Cancer Patients: Screening and Related Factors
Authors: Tseng Ya-Ting , Hsieh Chia-Hsun , Hung Chien-Wei , Chen Chia-Chia , Lee Shu-Hui , Lee Li-Yun , Chen Shu-Ching
Published: August 2021

Upper gastrointestinal (UGI) cancer treatment can cause physical and psychological distress and may result in unmet needs. The purposes of this study were to (1) examine the levels of gastrointestinal (GI) symptom distress, social support, and supportive care needs; (2) screen the priorities of unmet supportive care needs; and (3) identify the factors associated with supportive care needs among UGI cancer patients receiving chemotherapy. This cross-sectional study examined UGI cancer patients who received treatment from the outpatient chemotherapy department of a single cancer center in northern Taiwan. Questionnaires were used to collect data regarding GI symptom distress, social support, unmet needs, and supportive care needs. The top three unmet needs were “fears about the cancer spreading”, “uncertainty about the future”, and “being informed about things you can do to help yourself to get well”. Descriptive statistics examined the levels of GI symptom distress, social support, supportive care needs, and priorities of unmet supportive care needs. Stepwise regression was conducted to determine significant factors related to supportive care needs. Greater supportive care needs were found to be associated with higher levels of disease-related worries, increased treatment-related symptoms, and a lower level of physical performance. These factors explained 48.0% of the variance in supportive care needs. Disease-related worries and treatment-related symptoms strongly influence overall supportive care needs and each domain of supportive care needs. Symptom management and psychological support for patients receiving outpatient chemotherapy may help patients meet needs.
Perfectionism, Motives, and Barriers to Exercise from a Person-Oriented Approach
Authors: Vicent María , Sanmartín Ricardo , Gonzálvez Carolina , Vásconez-Rubio Oswaldo , García-Fernández José Manuel
Published: August 2021

Perfectionism is considered to be a significant personality factor within the sport and exercise field. However, very little is known about the reasons why individuals with different perfectionistic tendencies engage or not in physical activity. This study aims, from a person-oriented approach, to analyze if participation motives and barriers may differ among four perfectionistic profiles: Non-Perfectionists (low perfectionistic strivings, PS, and perfectionistic concerns, PC), Adaptive Perfectionists (high PS and low PC), Maladaptive Perfectionists (high PS and PC), and Moderate Perfectionists (moderate PS and PC). A sample composed of 597 (Mage = 22.08, SD = 3.33) undergraduates enrolled in a sport science degree from Ecuador participated in this study. Non-Perfectionists reported lower levels of motives, whereas Adaptive and Maladaptive Perfectionists reported higher scores on all participation motives. Significant and positive correlations were found between PS and both autonomous and controlled motives, whereas PC was positively correlated with controlled reasons and only significantly correlated with some autonomous reasons by the effect of PS. In terms of barriers, Maladaptive Perfectionists reported significantly higher scores on all barriers analyzed in comparison with the other three profiles, with moderate and large effect sizes. The results of the bivariate and partial correlations suggest that these inter-profile differences were explained by PC. Considering the results, it is advised to develop strategies to identify Maladaptive Perfectionists in order to increase their intrinsic reasons for practicing physical exercise, and to minimize their perceived barriers.
One Year of Online Education in COVID-19 Age, a Challenge for the Romanian Education System
Authors: Edelhauser Eduard , Lupu-Dima Lucian
Published: August 2021

The study tried to analyze the implication of one year of online education in the Romanian education system. To achieve this goal, the authors of this study analyzed all the levels of education, primary education, lower secondary education, upper secondary education, and even the early childhood system, but also one of the smallest Romanian universities, considered representative for grade 1 universities representing 60% of the Romanian universities. The study is based on four online questionnaires for investigation, first with more than 2500 respondents from the primary and secondary Romanian education system, and the other three applied to more than 800 students and professors from the University of Petroșani. The investigation took place during 29 January 2021 and 11 February 2021. The authors had investigated the main feature of a standard online or a classical e-learning solution, such as the meeting solution or the video conference software, the collaborative work, such as homework or projects, and the testing method or the quizzes from both perspectives of the students and of the professors. The study results could influence the expected future hybrid educational system because these results were not covered in the previous literature but proved to be necessary for relevant knowledge strategies to be implemented in the new pandemic and also in the future context.
Effects of Acute Beta-Alanine Ingestion and Immersion-Plus-Exercise on Connectedness to Nature and Perceived Pain
Authors: Salatto R. W. , McGinnis Graham R. , Davis Dustin W. , Carrier Bryson , Manning Jacob W. , DeBeliso Mark , Navalta James W.
Published: August 2021

This double-blinded, placebo-controlled, crossover study examined the effect of induced painful sensation (via acute Beta Alanine (B-ALA) ingestion) on Love and Care of Nature (LCN), heart rate (HR), rating of perceived exertion (RPE), and McGill Pain Questionnaire (MPQ) during outdoor exercise. Twenty participants volunteered on consecutive days to complete a 0.8 km (0.5 mi) up-hill hike after consuming either B-ALA (6.4 g) or placebo. Immediately after consumption participants answered LCN, RPE, and MPQ questionnaires, immersed in a natural environment for 45 min, and then completed a hike as quickly as possible without running. No difference in HR (p = 0.846), or RPE (p = 0.606) were observed between treatments. Total MPQ scores increased with consumption of B-ALA (p = 0.001). An increased LCN score was observed following exercise regardless of condition (p = 0.035). The results demonstrate that acute B-ALA supplementation is effective in increasing perceived pain sensations. The results also demonstrate an increase in LCN in the presence of increased perceptions of pain sensations during exercise.
Improving Millennial Employees’ OCB: A Multilevel Mediated and Moderated Model of Ethical Leadership
Authors: Su Wei , Hahn Juhee
Published: August 2021

In the field of organizational behavior, the influence of leadership in organizations and the organizational citizenship behavior (OCB) of employees have always been two hot topics studied by scholars. However, previous studies have mainly examined the OCB of baby boomers and Generation Xers. With millennials now entering the workforce, they will highly likely not take the initiative to engage in OCB due to their different values. Scholars have found that millennials respond well to ethical leadership. Although this statement has a theoretical basis, empirical research regarding this topic is still insufficient. Thus, this study explores whether ethical leadership can effectively promote millennials’ OCB. Moreover, the mediating effect of group-level ethical climate and individual-level affective well-being, and the moderating effect of individual-level moral identity, were examined. The study hypotheses were verified based on 384 valid questionnaires collected from 61 teams using Mplus 8.3. The results showed that (1) ethical leadership was a positive predictor of millennials’ OCB; (2) ethical climate and affective well-being partially mediated the relationship between ethical leadership and OCB; and (3) moral identity moderated the relationship between ethical leadership and affective well-being and the indirect impact of ethical leadership on OCB. These findings provide empirical support for applying social learning theory, social information processing theory, and conservation of resources (COR)theory. This research also provides several managerial implications through which managers can more effectively improve the OCB of millennial employees.
Understanding the Life, Pain, and Barriers to Physical Activity in Korean Patients with Panic Disorder: Photovoice Inquiry
Authors: Kim Kyung-O , Ryu Jae-Hyeong , Chung Hae-Ryong , Butler Marcia K. , Gritzmacher Deborah
Published: August 2021

Purpose: This study attempted to understand the life, pain, and barriers to physical activity in the daily life of patients with panic disorder (PD). It aimed to provide specific evidence to promote physical activity for patients, suggesting that suitable physical activity strategies for patients with PD would be of value. Methods: Seven patients were invited to participate in a photovoice study. Photovoice is one example of participatory action research. Results: This study inductively identified two main themes: the life and pain of patients with PD and perceived barriers to participate in physical activity by patients with panic disorder. Conclusion: Based on a specific understanding of the population, this study attempted to provide evidence why patients with panic disorder need appropriate physical-activity-promoting strategies.
Diet, Nutrition, and Oral Health: What Influences Mother’s Decisions on What to Feed Their Young Children?
Authors: Arora Amit , Chew Louise , Kang Kaye , Tang Lily , Estai Mohamed , Thepsourinthone Jack , Chandio Navira , Parmar Jinal , Doyizode Ashish M. , Jain K. Vipin , Bhole Sameer
Published: August 2021

The purpose of this study was to learn about mothers’ experiences with food choices for their pre-school children in underprivileged communities in Greater Western Sydney (GWS). A total of 20 mother-child dyads living in GWS were recruited to a qualitative study from an ongoing birth cohort study. Participants’ houses were visited for semi-structured interviews, which were recorded, transcribed verbatim, and analysed thematically. The interviews yielded five main themes: (i) food choices, nutrition, and health; (ii) accessibility and availability of foods (iii) buying time for parents; (iv) child’s age and their preference on food choices; (v) conditioning certain behaviours by family and cultural factors. Nutrition literacy, child’s preferences, unhealthy food intake by family members, child’s demand, advertising and availability of harmful foods, and time constraints were all mentioned as hurdles to mothers making appropriate meal choices for their children. However, some identified facilitators were promoting parents’ knowledge, increasing access to health educational materials, upskilling mothers to providing healthier alternatives, regulating the marketing of unhealth foods. Although, the present study identified critical factors that influence mothers’ food choices for their young children, making healthy food choices is a complex practice as it is shaped by individual, social and environmental influences.
Cancer Healthcare Workers’ Perceptions toward Psychedelic-Assisted Therapy: A Preliminary Investigation
Authors: Reynolds Lisa M. , Akroyd Amelia , Sundram Frederick , Stack Aideen , Muthukumaraswamy Suresh , Evans William J.
Published: August 2021

Recent clinical trials suggest that psychedelic-assisted therapy is a promising intervention for reducing anxiety and depression and ameliorating existential despair in advanced cancer patients. However, little is known about perceptions toward this treatment from the key gatekeepers to this population. The current study aimed to understand the perceptions of cancer healthcare professionals about the potential use of psychedelic-assisted therapy in advanced cancer patients. Twelve cancer healthcare professionals including doctors, nurses, psychologists and social workers took part in a semi-structured interview which explored their awareness and perceptions toward psychedelic-assisted therapy with advanced cancer patients. Data were analysed using thematic analysis. Four inter-connected themes were identified. Two themes relate to the role and responsibility of being a cancer healthcare worker: (1) ‘beneficence: a need to alleviate the suffering of cancer patients’ and (2) ‘non-maleficence: keeping vulnerable cancer patients safe’, and two themes relate specifically to the potential for psychedelic-assisted therapy as (3) ‘a transformative approach with the potential for real benefit’ but that (4) ‘new frontiers can be risky endeavours’. The findings from this study suggest intrigue and openness in cancer healthcare professionals to the idea of utilising psychedelic-assisted therapy with advanced cancer patients. Openness to the concept appeared to be driven by a lack of current effective treatment options and a desire to alleviate suffering. However, acceptance was tempered by concerns around safety and the importance of conducting rigorous, well-designed trials. The results from this study provide a useful basis for engaging with healthcare professionals about future research, trial design and potential clinical applications.
Association of Regular Leisure-Time Physical Activity with Happiness among Middle-Aged and Older Adults in Taiwan
Authors: Liang Chyi , Wu Pei-Ling , Lee Po-Fu , Ho Chien-Chang
Published: August 2021

The aim of the present study was to clarify the relationship between regular LTPA (i.e., 150–300 min of moderate-intensity or 75–150 min of high-intensity physical activity) and happiness among middle-aged and older adults in Taiwan. The cross-sectional study data were obtained from the Taiwan National Physical Activity Survey, a nationally representative survey of the Taiwanese population. A total of 12,687 middle-aged and older adults (45–108 years) were ultimately enrolled in this study. The questionnaire data obtained through this national telephone survey included sociodemographic characteristics, self-reported health status, self-evaluations (comprising height, body weight, and happiness), and zip code of residence. The results suggest a significant positive relationship between regular LTPA and happiness scores; that is, the middle-aged adults who engaged in more LTPA may report higher happiness occurrence than others. This study suggests that regular LTPA is an essential factor influencing happiness. LTPA is an essential form of physical activity that helps middle-aged and older people to relax.
A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease
Authors: de Haan Luuk , Suijker Johnny , van Roey Ruthger , Berges Nina , Petrova Elissaveta , Queiroz Karla , Strijker Wouter , Olivier Thomas , Poeschke Oliver , Garg Sakshi , van den Broek Lenie J.
Published: August 2021

The recruitment of T cells is a crucial component in the inflammatory cascade of the body. The process involves the transport of T cells through the vascular system and their stable arrest to vessel walls at the site of inflammation, followed by extravasation and subsequent infiltration into tissue. Here, we describe an assay to study 3D T cell dynamics under flow in real time using a high-throughput, artificial membrane-free microfluidic platform that allows unimpeded extravasation of T cells. We show that primary human T cells adhere to endothelial vessel walls upon perfusion of microvessels and can be stimulated to undergo transendothelial migration (TEM) by TNFα-mediated vascular inflammation and the presence of CXCL12 gradients or ECM-embedded melanoma cells. Notably, migratory behavior was found to differ depending on T cell activation states. The assay is unique in its comprehensiveness for modelling T cell trafficking, arrest, extravasation and migration, all in one system, combined with its throughput, quality of imaging and ease of use. We envision routine use of this assay to study immunological processes and expect it to spur research in the fields of immunological disorders, immuno-oncology and the development of novel immunotherapeutics.
Effects of Cancer Presence and Therapy on the Platelet Proteome
Authors: Walraven Maudy , Sabrkhany Siamack , Knol Jaco , Dekker Henk , de Reus Inge , Piersma Sander , Pham Thang , Griffioen Arjan , Broxterman Henk , Oude Egbrink Mirjam , Verheul Henk , Jimenez Connie
Published: August 2021

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome.
Imaging of C-fos Activity in Neurons of the Mouse Parietal Association Cortex during Acquisition and Retrieval of Associative Fear Memory
Authors: Ivashkina Olga I. , Gruzdeva Anna M. , Roshchina Marina A. , Toropova Ksenia A. , Anokhin Konstantin V.
Published: August 2021

The parietal cortex of rodents participates in sensory and spatial processing, movement planning, and decision-making, but much less is known about its role in associative learning and memory formation. The present study aims to examine the involvement of the parietal association cortex (PtA) in associative fear memory acquisition and retrieval in mice. Using ex vivo c-Fos immunohistochemical mapping and in vivo Fos-EGFP two-photon imaging, we show that PtA neurons were specifically activated both during acquisition and retrieval of cued fear memory. Fos immunohistochemistry revealed specific activation of the PtA neurons during retrieval of the 1-day-old fear memory. In vivo two-photon Fos-EGFP imaging confirmed this result and in addition detected specific c-Fos responses of the PtA neurons during acquisition of cued fear memory. To allow a more detailed study of the long-term activity of such PtA engram neurons, we generated a Fos-Cre-GCaMP transgenic mouse line that employs the Targeted Recombination in Active Populations (TRAP) technique to detect calcium events specifically in cells that were Fos-active during conditioning. We show that gradual accumulation of GCaMP3 in the PtA neurons of Fos-Cre-GCaMP mice peaks at the 4th day after fear learning. We also describe calcium transients in the cell bodies and dendrites of the TRAPed neurons. This provides a proof-of-principle for TRAP-based calcium imaging of PtA functions during memory processes as well as in experimental models of fear- and anxiety-related psychiatric disorders and their specific therapies.
Comparison of Silks from Pseudoips prasinana and Bombyx mori Shows Molecular Convergence in Fibroin Heavy Chains but Large Differences in Other Silk Components
Authors: Rindos Michal , Kucerova Lucie , Rouhova Lenka , Sehadova Hana , Sery Michal , Hradilova Miluse , Konik Peter , Zurovec Michal
Published: August 2021

Many lepidopteran larvae produce silk feeding shelters and cocoons to protect themselves and the developing pupa. As caterpillars evolved, the quality of the silk, shape of the cocoon, and techniques in forming and leaving the cocoon underwent a number of changes. The silk of Pseudoips prasinana has previously been studied using X-ray analysis and classified in the same category as that of Bombyx mori, suggesting that silks of both species have similar properties despite their considerable phylogenetic distance. In the present study, we examined P. prasinana silk using ‘omics’ technology, including silk gland RNA sequencing (RNA-seq) and a mass spectrometry-based proteomic analysis of cocoon proteins. We found that although the central repetitive amino acid sequences encoding crystalline domains of fibroin heavy chain molecules are almost identical in both species, the resulting fibers exhibit quite different mechanical properties. Our results suggest that these differences are most probably due to the higher content of fibrohexamerin and fibrohexamerin-like molecules in P. prasinana silk. Furthermore, we show that whilst P. prasinana cocoons are predominantly made of silk similar to that of other Lepidoptera, they also contain a second, minor silk type, which is present only at the escape valve.
Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime?
Authors: Vásquez Ximena , Sánchez-Gómez Pilar , Palma Verónica
Published: August 2021

Glioblastoma (GBM) is the most aggressive and common primary tumor of the central nervous system. It is characterized by having an infiltrating growth and by the presence of an excessive and aberrant vasculature. Some of the mechanisms that promote this neovascularization are angiogenesis and the transdifferentiation of tumor cells into endothelial cells or pericytes. In all these processes, the release of extracellular microvesicles by tumor cells plays an important role. Tumor cell-derived extracellular microvesicles contain pro-angiogenic molecules such as VEGF, which promote the formation of blood vessels and the recruitment of pericytes that reinforce these structures. The present study summarizes and discusses recent data from different investigations suggesting that Netrin-1, a highly versatile protein recently postulated as a non-canonical angiogenic ligand, could participate in the promotion of neovascularization processes in GBM. The relevance of determining the angiogenic signaling pathways associated with the interaction of Netrin-1 with its receptors is posed. Furthermore, we speculate that this molecule could form part of the microvesicles that favor abnormal tumor vasculature. Based on the studies presented, this review proposes Netrin-1 as a novel biomarker for GBM progression and vascularization.
A Facile Strategy to Prepare Small Water Clusters via Interacting with Functional Molecules
Authors: Zhang Shanmeiyu , Zhang Yanyan , Wu Chongchong , Yang Hui , Zhang Qiqi , Wang Fuyi , Wang Jingyi , Gates Ian , Wang Jinben
Published: August 2021

Although small water clusters (SWCs) are important in many research fields, efficient methods of preparing SWCs are still rarely reported, which is mainly due to the lack of related materials and understanding of the molecular interaction mechanisms. In this study, a series of functional molecules were added in water to obtain small water cluster systems. The decreasing rate of the half-peak width in a sodium dodecyl sulfate (SDS)–water system reaches ≈20% at 0.05 mM from 17O nuclear magnetic resonance (NMR) results. Based on density functional theory (DFT) and molecular dynamics (MD) simulation calculation, it can be concluded that functional molecules with stronger negative electrostatic potential (ESP) and higher hydrophilicity have a stronger ability to destroy big water clusters. Notably, the concentrations of our selected molecule systems are one to two magnitudes lower than that of previous reports. This study provides a promising way to optimize aqueous systems in various fields such as oilfield development, protein stability, and metal anti-corrosion.
DIA-Based Quantitative Proteomics Reveals the Protein Regulatory Networks of Floral Thermogenesis in Nelumbo nucifera
Authors: Sun Yueyang , Zou Yu , Jin Jing , Chen Hao , Liu Zhiying , Zi Qinru , Xiong Zeyang , Wang Ying , Li Qian , Peng Jing , Ding Yi
Published: August 2021

The sacred lotus (Nelumbo nucifera) can maintain a stable floral chamber temperature between 30 and 35 °C when blooming despite fluctuations in ambient temperatures between about 8 and 45 °C, but the regulatory mechanism of floral thermogenesis remains unclear. Here, we obtained comprehensive protein profiles from receptacle tissue at five developmental stages using data-independent acquisition (DIA)-based quantitative proteomics technology to reveal the molecular basis of floral thermogenesis of N. nucifera. A total of 6913 proteins were identified and quantified, of which 3513 differentially abundant proteins (DAPs) were screened. Among them, 640 highly abundant proteins during the thermogenic stages were mainly involved in carbon metabolism processes such as the tricarboxylic acid (TCA) cycle. Citrate synthase was identified as the most connected protein in the protein-protein interaction (PPI) network. Next, the content of alternative oxidase (AOX) and plant uncoupling protein (pUCP) in different tissues indicated that AOX was specifically abundant in the receptacles. Subsequently, a protein module highly related to the thermogenic phenotype was identified by the weighted gene co-expression network analysis (WGCNA). In summary, the regulation mechanism of floral thermogenesis in N. nucifera involves complex regulatory networks, including TCA cycle metabolism, starch and sucrose metabolism, fatty acid degradation, and ubiquinone synthesis, etc.
Revisiting the Proposition of Binding Pockets and Bioactive Poses for GSK-3β Allosteric Modulators Addressed to Neurodegenerative Diseases
Authors: Silva Guilherme M. , Borges Rosivaldo S. , Santos Kelton L. B. , Federico Leonardo B. , Francischini Isaque A. G. , Gomes Suzane Q. , Barcelos Mariana P. , Silva Rai C. , Santos Cleydson B. R. , Silva Carlos H. T. P.
Published: August 2021

Glycogen synthase kinase-3 beta (GSK-3β) is an enzyme pertinently linked to neurodegenerative diseases since it is associated with the regulation of key neuropathological features in the central nervous system. Among the different kinds of inhibitors of this kinase, the allosteric ones stand out due to their selective and subtle modulation, lowering the chance of producing side effects. The mechanism of GSK-3β allosteric modulators may be considered still vague in terms of elucidating a well-defined binding pocket and a bioactive pose for them. In this context, we propose to reinvestigate and reinforce such knowledge by the application of an extensive set of in silico methodologies, such as cavity detection, ligand 3D shape analysis and docking (with robust validation of corresponding protocols), and molecular dynamics. The results here obtained were consensually consistent in furnishing new structural data, in particular by providing a solid bioactive pose of one of the most representative GSK-3β allosteric modulators. We further applied this to the prospect for new compounds by ligand-based virtual screening and analyzed the potential of the two obtained virtual hits by quantum chemical calculations. All potential hits achieved will be subsequently tested by in vitro assays in order to validate our approaches as well as to unveil novel chemical entities as GSK-3β allosteric modulators.
Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors
Authors: Molagoda Ilandarage Menu Neelaka , Kavinda Mirissa Hewage Dumindu , Ryu Hyung Won , Choi Yung Hyun , Jeong Jin-Woo , Kang Sanghyuck , Kim Gi-Young
Published: August 2021

Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (MITF) and tyrosinase expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABAA and GABAB receptors, with subsequent inhibition of Ca2+ accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABAA receptor antagonist, and CGP 46381, a GABAB receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca2+ accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders.
Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging
Authors: Uddin Md Jamal , Farjana Mithila , Moni Akhi , Hossain Khandkar Shaharina , Hannan Md. Abdul , Ha Hunjoo
Published: August 2021

Aging is an unavoidable part of life. The more aged we become, the more susceptible we become to various complications and damages to the vital organs, including the kidneys. The existing drugs for kidney diseases are mostly of synthetic origins; thus, natural compounds with minimal side-effects have attracted growing interest from the scientific community and pharmaceutical companies. A literature search was carried out to collect published research information on the effects of resveratrol on kidney aging. Recently, resveratrol has emerged as a potential anti-aging agent. This versatile polyphenol exerts its anti-aging effects by intervening in various pathologies and multi-signaling systems, including sirtuin type 1, AMP-activated protein kinase, and nuclear factor-κB. Researchers are trying to figure out the detailed mechanisms and possible resveratrol-mediated interventions in divergent pathways at the molecular level. This review highlights (i) the causative factors implicated in kidney aging and the therapeutic aspects of resveratrol, and (ii) the effectiveness of resveratrol in delaying the aging process of the kidney while minimizing all possible side effects.
Optical Properties of Composites Based on Poly(o-phenylenediamine), Poly(vinylenefluoride) and Double-Wall Carbon Nanotubes
Authors: Baibarac Mihaela , Daescu Monica , Matei Elena , Nastac Daniela , Cramariuc Oana
Published: August 2021

In this work, synthesis and optical properties of a new composite based on poly(o-phenylenediamine) (POPD) fiber like structures, poly(vinylidene fluoride) (PVDF) spheres and double-walled carbon nanotubes (DWNTs) are reported. As increasing the PVDF weight in the mixture of the chemical polymerization reaction of o-phenylenediamine, the presence of the PVDF spheres onto the POPD fibers surface is highlighted by scanning electron microscopy (SEM). The down-shift of the Raman line from 1421 cm−1 to 1415 cm−1 proves the covalent functionalization of DWNTs with the POPD-PVDF blends. The changes in the absorbance of the IR bands peaked around 840, 881, 1240 and 1402 cm−1 indicate hindrance steric effects induced of DWNTs to the POPD fiber like structures and the PVDF spheres, as a consequence of the functionalization process of carbon nanotubes with macromolecular compounds. The presence of the PVDF spheres onto the POPD fiber like structures surface induces a POPD photoluminescence (PL) quenching process. An additional PL quenching process of the POPD-PVDF blends is reported to be induced in the presence of DWNTs. The studies of anisotropic PL highlight a change of the angle of the binding of the PVDF spheres onto the POPD fiber like structures surface from 50.2° to 38° when the carbon nanotubes concentration increases in the POPD-PVDF/DWNTs composites mass up to 2 wt.%.
Features of Lipid Metabolism in Humanized ApoE Knockin Rat Models
Authors: Wu Yang , Johnson Gem , Zhao Fujie , Wu Yin , Zhao Guojun , Brown Andrew , You Shaojin , Zou Ming-Hui , Song Ping
Published: August 2021

Apolipoprotein E (ApoE), an essential plasma apolipoprotein, has three isoforms (E2, E3, and E4) in humans. E2 is associated with type III hyperlipoproteinemia. E4 is the major susceptibility gene to Alzheimer’s disease (AD) and coronary heart disease (CHD). We investigated lipid metabolism and atherosclerotic lesions of novel humanized ApoE knockin (hApoE KI) rats in comparison to wide-type (WT) and ApoE knockout (ApoE KO) rats. The hApoE2 rats showed the lowest bodyweight and white fat mass. hApoE2 rats developed higher serum total cholesterol (TC), total triglyceride (TG), and low- and very low density lipoprotein (LDL-C&VLDL-C). ApoE KO rats also exhibited elevated TC and LDL-C&VLDL-C. Only mild atherosclerotic lesions were detected in hApoE2 and ApoE KO aortic roots. Half of the hApoE2 rats developed hepatic nodular cirrhosis. A short period of the Paigen diet (PD) treatment led to the premature death of the hApoE2 and ApoE KO rats. Severe vascular wall thickening of the coronary and pulmonary arteries was observed in 4-month PD-treated hApoE4 rats. In conclusion, hApoE2 rats develop spontaneous hyperlipidemia and might be suitable for studies of lipid metabolism-related diseases. With the PD challenge, hApoE4 KI rats could be a novel model for the analysis of vascular remodeling.
Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast
Authors: Knyazev Nickolay A. , Shmakov Stanislav V. , Pechkovskaya Sofya A. , Filatov Alexander S. , Stepakov Alexander V. , Boitsov Vitali M. , Filatova Natalia A.
Published: August 2021

Novel heterocyclic compounds containing 3-spiro[3-azabicyclo[3.1.0]hexane]oxindole framework (4a, 4b and 4c) have been studied as potential antitumor agents. The in silico ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed on 4a–c compounds with promising antiproliferative activity, previously synthetized and screened against human erythroleukemic cell line K562 tumor cell line. Cytotoxicity of 4a–c against murine fibroblast 3T3 and SV-40 transformed murine fibroblast 3T3-SV40 cell lines were evaluated. The 4a and 4c compounds were cytotoxic against 3T3-SV40 cells in comparison with those of 3T3. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Using confocal microscopy, we found that with 4a and 4c treatment of 3T3 cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 82–97% of cells. The number of 3T3-SV40 cells with stress fibers increased to 7–30% against 2% in control. We discovered that transformed 3T3-SV40 cells after treatment with compounds 4a and 4c significantly reduced the number of cells with filopodium-like membrane protrusions (from 86 % in control cells to 6–18% after treatment), which indirectly suggests a decrease in cell motility. We can conclude that the studied compounds 4a and 4c have a cytostatic effect, which can lead to a decrease in the number of filopodium-like membrane protrusions.
High-Throughput Phenotyping Methods for Breeding Drought-Tolerant Crops
Authors: Kim Minsu , Lee Chaewon , Hong Subin , Kim Song Lim , Baek Jeong-Ho , Kim Kyung-Hwan
Published: August 2021

Drought is a main factor limiting crop yields. Modern agricultural technologies such as irrigation systems, ground mulching, and rainwater storage can prevent drought, but these are only temporary solutions. Understanding the physiological, biochemical, and molecular reactions of plants to drought stress is therefore urgent. The recent rapid development of genomics tools has led to an increasing interest in phenomics, i.e., the study of phenotypic plant traits. Among phenomic strategies, high-throughput phenotyping (HTP) is attracting increasing attention as a way to address the bottlenecks of genomic and phenomic studies. HTP provides researchers a non-destructive and non-invasive method yet accurate in analyzing large-scale phenotypic data. This review describes plant responses to drought stress and introduces HTP methods that can detect changes in plant phenotypes in response to drought.
Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia
Authors: Brennan Steven K , Ferkol Thomas W , Davis Stephanie D
Published: August 2021

Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.
Computational Investigation of the pH Dependence of Stability of Melanosome Proteins: Implication for Melanosome formation and Disease
Authors: Koirala Mahesh , Shashikala H. B. Mihiri , Jeffries Jacob , Wu Bohua , Loftus Stacie K. , Zippin Jonathan H. , Alexov Emil
Published: August 2021

Intravesicular pH plays a crucial role in melanosome maturation and function. Melanosomal pH changes during maturation from very acidic in the early stages to neutral in late stages. Neutral pH is critical for providing optimal conditions for the rate-limiting, pH-sensitive melanin-synthesizing enzyme tyrosinase (TYR). This dramatic change in pH is thought to result from the activity of several proteins that control melanosomal pH. Here, we computationally investigated the pH-dependent stability of several melanosomal membrane proteins and compared them to the pH dependence of the stability of TYR. We confirmed that the pH optimum of TYR is neutral, and we also found that proteins that are negative regulators of melanosomal pH are predicted to function optimally at neutral pH. In contrast, positive pH regulators were predicted to have an acidic pH optimum. We propose a competitive mechanism among positive and negative regulators that results in pH equilibrium. Our findings are consistent with previous work that demonstrated a correlation between the pH optima of stability and activity, and they are consistent with the expected activity of positive and negative regulators of melanosomal pH. Furthermore, our data suggest that disease-causing variants impact the pH dependence of melanosomal proteins; this is particularly prominent for the OCA2 protein. In conclusion, melanosomal pH appears to affect the activity of multiple melanosomal proteins.
Probiotic-Induced Tolerogenic Dendritic Cells: A Novel Therapy for Inflammatory Bowel Disease?
Authors: Baradaran Ghavami Shaghayegh , Asadzadeh Aghdaei Hamid , Sorrentino Dario , Shahrokh Shabnam , Farmani Maryam , Ashrafian Fatemeh , Dore Maria Pina , Keshavarz Azizi Raftar Shahrbanoo , Mobin Khoramjoo Seyed , Zali Mohammad Reza
Published: August 2021

Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs’ maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.
Phytochemicals in Malignant Pleural Mesothelioma Treatment—Review on the Current Trends of Therapies
Authors: Chmielewska-Kassassir Malgorzata , Wozniak Lucyna A.
Published: August 2021

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.