bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Activity during Pregnancy and Newborn Body Composition: A Systematic Review
Authors: Menke Brenna R. , Duchette Cathryn , Tinius Rachel A. , Wilson Alexandria Q. , Altizer Elizabeth A. , Maples Jill M.
Published: June 2022

The current literature demonstrates that not only is exercise during pregnancy safe, but it has substantial maternal and infant benefits and appears to influence infant growth/size throughout pregnancy and at birth. However, many existing studies have investigated only the effects of prenatal exercise on birth weight. The purpose of this review was to determine the impact or association of maternal physical activity during pregnancy on neonatal body composition assessed between birth and two weeks of age. Electronic database searches were conducted on 29 July 2019 for randomized control trials and cohort studies, with an updated search completed on 8 January 2021. A total of 32 articles that met eligibility criteria were selected for review. Overall, prenatal exercise was not associated with infant body composition at birth. Yet, five of the studies identified suggest that infant body composition could be influenced by higher volumes of mid-to-late term prenatal physical activity. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (Registration No. CRD42020160138).
Creating a Healthy Environment for Children: GIS Tools for Improving the Quality of the Social Welfare Management System
Authors: Źróbek-Różańska Alina , Ogryzek Marek , Źróbek-Sokolnik Anna
Published: June 2022

Childhood is considered to be the most vital period for mental, physical, and social development. Even short-term deprivation of nutrition, health care, education, and affection in childhood can have long-term and irreversible negative consequences. Various social assistance programs are being launched around the world to eliminate or alleviate social problems, including those experienced by children in their immediate environment. Different solutions have been proposed around the world, but welfare systems in all countries share the following common features: social assistance is necessary and underfinanced, and social workers struggle to cope with caseloads. As a result, welfare work is stressful and not highly effective. In this study, modern Geographic Information System (GIS) tools for supporting the employees of social assistance centers (SACs) have been proposed. The data relating to welfare beneficiaries were analyzed by nonparametric kernel density estimation and divided into five datasets. The kernel density tool in ArcGIS Pro software (Esri Polska sp. z o.o., Warsaw, Poland) was used to visualize areas with a relatively high prevalence of social problems, as well as areas where the neighborhood can deliver synergistic effects. A multicriteria analysis (MCA) procedure for mapping social problems was proposed, and an algorithm was developed in the GIS environment. The generated maps deliver helpful information for supporting SAC employees, as well as monitoring, planning, and initiating preventive measures. Above all, the presented method was designed to improve living conditions by facilitating the management of welfare workers’ duties. Therefore, the proposed approach had to be effective and easy to use without an advanced knowledge of GIS tools.
Bullying Victimization and Mental Health among Migrant Children in Urban China: A Moderated Mediation Model of School Belonging and Resilience
Authors: Nie Wei , Gao Liru , Cui Kunjie
Published: June 2022

School bullying victimization among children is a significant public health issue that may negatively influence their mental health. However, few studies have been conducted on the bullying of migrant children in urban China. A positive psychological perspective has rarely been adopted in examining the mechanisms through which bullying victimization influences mental health, and the protective factors remain understudied. This research investigates the factors that may contribute to reducing the negative effects of bullying victimization on mental health, focusing on the protective roles of school belonging and resilience in the association between bullying victimization and mental health. Data were collected from 1087 school-aged migrant children in Shanghai and Nanjing, China. The PROCESS macro was used to conduct moderated mediation analyses to test the hypothesized models. The results of moderated mediation modeling revealed that bullying victimization (β = −0.386, p < 0.001) was negatively linked with mental health through decreased school belonging (β = 0.398, p < 0.001). Moreover, resilience buffered the indirect negative effects of bullying victimization on migrant children’s mental health via school belonging (β = −0.460, p < 0.01). Specifically, lower resilience was clearly associated with stronger indirect effects. Our findings suggest that school belonging and resilience must be incorporated into mental health prevention and intervention programs targeting migrant children with bullying victimization experiences.
Dispersion Stability of 14 Manufactured Nanomaterials for Ecotoxicity Tests Using Raphidocelis subcapitata
Authors: Lee Seung-Hun , Jung Kiyoon , Yoo Won Cheol , Chung Jinwook , Lee Yong-Woo
Published: June 2022

The development of nanotechnology has increased concerns about the exposure of ecosystems to manufactured nanomaterials, the toxicities of which are now being researched. However, when manufactured nanomaterials are mixed with algae in a culture medium for ecotoxicity tests, the results are vulnerable to distortion by an agglomeration phenomenon. Here, we describe a dispersion method commonly applicable to ecotoxicity tests for the 14 types of manufactured nanomaterials specified by the Organisation of Economic Co-operation and Development’s Sponsorship Programme, namely aluminum oxide (Al2O3), carbon black, single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), cerium oxide (CeO2), dendrimers, fullerene, gold (Au), iron (Fe), nanoclays, silver (Ag), silicon dioxide (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO). The type of dispersant, sonication time, and stirring speed were carefully considered. Consequently, 1500 mg/L of gum arabic was selected as a dispersant; for sonication time, 1 h was selected for dendrimers, 2 h for SiO2, 24 h for SWCNTs and Au, and 4 h for the other nanomaterials. Dispersion stability was achieved for all materials at a stirring speed of 200 rpm. To verify the effect of this dispersion method on ecotoxicity tests, toxicity was measured through cell counts for SWCNTs and TiO2 using Raphidocelis subcapitata. The half-maximal effective concentrations (EC50) were 18.0 ± 4.6 mg/L for SWCNTs and 316.6 ± 64.7 mg/L for TiO2.
Synergic Benefits of Air Pollutant Reduction, CO2 Emission Abatement, and Water Saving under the Goal of Achieving Carbon Emission Peak: The Case of Tangshan City, China
Authors: Yang Rupu , Wang Min , Zhao Mengxue , Feng Xiangzhao
Published: June 2022

The study aims to explore the synergic benefits of reducing air pollutants and CO2 and water consumption under the carbon emission peak (CEP) policies at a city level. Air pollutants and CO2 emissions are predicted by the Low Emissions Analysis Platform (LEAP) model, and the water consumption is forecast by the quota method. Two scenarios are constructed with the same policies, but to different degrees: the reference scenario achieves CEP in 2030, and the green and low carbon scenario achieves CEP in 2025. The prediction results show that air pollutant emissions, CO2 emissions, and water consumption can be obviously decreased by intensifying the CEP policies. The synergic abatement effect was illustrated by the synergic reduction curve. Accelerating the adjustment of economic structure saves the most water, reduces the greatest amount of CO2 emission, and also obtains the best synergic reduction capability between water consumption and CO2 emission. Transforming the traditionally long process of steelmaking toward a short electric process reduces the majority of PM2.5, SO2, and VOC emissions, while consuming more water. The study provides a new viewpoint to assess and optimize the CEP action plan at city levels.
Evaluating the Effectiveness of the COVID-19 Emergency Outbreak Prevention and Control Based on CIA-ISM
Authors: Wang Renlong , Wang Endong , Li Lingzhi , Li Wei
Published: June 2022

The COVID-19 pandemic, characterized by high uncertainty and difficulty in prevention and control, has caused significant disasters in human society. In this situation, emergency management of pandemic prevention and control is essential to reduce the pandemic’s devastation and rapidly restore economic and social stability. Few studies have focused on a scenario analysis of the entire emergency response process. To fill this research gap, this paper applies a cross impact analysis (CIA) and interpretive structural modeling (ISM) approach to analyze emergency scenarios and evaluate the effectiveness of emergency management during the COVID-19 crisis for outbreak prevention and control. First, the model extracts the critical events for COVID-19 epidemic prevention and control, including source, process, and resultant events. Subsequently, we generated different emergency management scenarios according to different impact levels and conducted scenario deduction and analysis. A CIA-ISM based scenario modeling approach is applied to COVID-19 emergency management in Nanjing city, China, and the results of the scenario projection are compared with actual situations to prove the validity of the approach. The results show that CIA-ISM based scenario modeling can realize critical event identification, scenario generation, and evolutionary scenario deduction in epidemic prevention and control. This method effectively handles the complexity and uncertainty of epidemic prevention and control and provides insights that can be utilized by emergency managers to achieve effective epidemic prevention and control.
‘I Was Present but I Was Absent’: Perceptions and Experiences of the Non-Medical Use of Prescription or over the Counter Medication among Employed South African Women
Authors: Harker Nadine , Erasmus Jodilee , Lucas Warren , Deitz Diane , Brooke-Sumner Carrie
Published: June 2022

Background: The need for workplace substance use prevention programmes globally and in South Africa is driven by the growing problem of substance use and the associated burden on the health and welfare of employees, their families and organizations. Substance use, which include the non-medical use of medications (both prescription and over-the counter), remains widespread and is a major cause of mortality and a risk factor for non-communicable diseases (NCDs). Method: Twenty in-depth semi-structured qualitative interviews were conducted with employed women in treatment or shortly out of treatment for the non-medically indicated use of over the counter or/and prescription medications (NMIU). These interviews were conducted face-to face with women residing in the Western and Eastern Cape provinces of South Africa. Thematic analysis using NVIVO was used to analyse data collected. Results: The findings from this study suggest that previous use of legal or illegal substances and challenging life experiences underpin pathways to the non-medical use of over-the-counter and prescription medications among employed women. Factors found to contribute to misuse relate to a lack of understanding on risks, and health professional prescribing practices, while mitigators to harmful use were related to increased awareness and understanding harmful practices, the need for improved access and referral to specialist treatment as well as prevention programmes for women. Conclusion: With the improved understanding of the issues surrounding the NMIU of over-the-counter and prescription medications among employed women, the need for interventions to prevent misuse and inadvertently dependency is highlighted.
Financial Support for Agriculture, Chemical Fertilizer Use, and Carbon Emissions from Agricultural Production in China
Authors: Guo Lili , Guo Sihang , Tang Mengqian , Su Mengying , Li Houjian
Published: June 2022

In the past 15 years, China has emitted the most carbon dioxide globally. The overuse of chemical fertilizer is an essential reason for agricultural carbon emissions. In recent years, China has paid more and more attention to financial support for agriculture. Therefore, understanding the relationship between chemical fertilizer use, financial support for agriculture, and agricultural carbon emissions will benefit sustainable agricultural production. To achieve the goal of our research, we selected the panel data of 30 provinces (cities) in China from 2000 to 2019 and employed a series of methods in this research. The results demonstrate that: the effect of chemical fertilizer consumption on agricultural carbon emissions is positive. Moreover, financial support for agriculture has a significantly positive impact on reducing carbon emissions from agricultural production. In addition, the results of causality tests testify to one−way causality from financial support for agriculture to carbon emissions from agricultural production, the bidirectional causal relationship between chemical fertilizer use and financial support for agriculture, and two−way causality between chemical fertilizer use and agricultural carbon emissions. Furthermore, the results of variance decomposition analysis represent that financial support for agriculture will significantly affect chemical fertilizer use and carbon emissions in the agricultural sector over the next decade. Finally, we provide several policy suggestions to promote low−carbon agricultural production based on the results of this study. The government should uphold the concept of sustainable agriculture, increase financial support for environmental−friendly agriculture, and encourage the research and use of cleaner agricultural production technologies and chemical fertilizer substitutes.
Adolescent Experiences of the COVID-19 Pandemic and School Closures and Implications for Mental Health, Peer Relationships and Learning: A Qualitative Study in South-West England
Authors: Widnall Emily , Adams Emma A. , Plackett Ruth , Winstone Lizzy , Haworth Claire M. A. , Mars Becky , Kidger Judi
Published: June 2022

The COVID-19 ‘lockdown’ and multiple school closures disrupted the daily lives and routines of the entire UK population. However, adolescents were likely particularly impacted by such measures due to this time being key for social and educational development. This qualitative study explored young people’s experiences of lockdowns and school closures. Fifteen secondary schools within south-west England were initially contacted and three schools participated in recruitment efforts. From December 2020 to March 2021, 25 students aged 14–15 participated in a combination of individual interviews (n = 5) and focus groups (n = 3). Findings revealed diverse experiences of the pandemic and highlighted the complexity of experiences according to individual student contexts. Three main themes were identified: (1) Learning environments; (2) Connection to peers; (3) Transition, adaptation and coping. These findings highlight the value young people place on face-to-face social contact with close friends, and the sense of structure provided by school, with implications for future home-based learning. Further in-depth qualitative research is needed to continue to understand the varied experiences during the course of the pandemic, particularly longer-term impacts on mental health and learning.
Well-Being in the Context of COVID-19 and Quality of Life in Czechia
Authors: Maturkanič Patrik , Tomanová Čergeťová Ivana , Konečná Irena , Thurzo Vladimír , Akimjak Amantius , Hlad Ľubomír , Zimny Jan , Roubalová Marie , Kurilenko Victoria , Toman Martin , Petrikovič Jozef , Petrikovičová Lucia
Published: June 2022

The present study focuses on exploring the differences and relationship between well-being and experience of pastoral and psychological service of religious denomination based on religious affiliation during the first wave of the pandemic in Czechia. Our research has been focused on the investigation, comparison, and correlation between the level of well-being and pastoral and psychological service. The research sample (n = 1126) consisted of the Czech health population with age over 16 years, of which 42.4% were men (n = 478) and 57.5% were women (n = 648). From the perspective of religiosity, the study sample was divided in terms of religion into two groups—51.9% participants with religious affiliation (n = 584) and 48.1% participants without religious affiliation (n = 542). The level of well-being was identified by means of The Satisfaction with Life Scale (Diener, Emmons, Larsen, & Griffin, 1985). The level of experience with pastoral and psychological service was measured using our non-standardised questionnaire. The results confirmed the differences between the variables of well-being and positive experience with pastoral and psychological service based on religious affiliation. Moreover, we confirmed the hypothesis of a positive correlation between well-being and positive experience with pastoral and psychological service in Czechia.
Potential of the Geometric Layer in Urban Digital Twins
Authors: Scalas Andreas , Cabiddu Daniela , Mortara Michela , Spagnuolo Michela
Published: June 2022

A urban digital twin is the virtual representation of real assets, processes, systems and subsystems of a city. It uses and integrates heterogeneous data to learn and evolve with the physical city, providing support to monitor the current status and predict/anticipate possible future scenarios. In this paper, we focus on the issues and potential related to the geometric layer of the city digital twin. On the one hand, detailed 3D data to reconstruct the urban morphology very accurately might not be available, and planning a new survey is costly in terms of money and time. On the other hand, the more the geometry adheres to the real counterpart, the more accurate measures and simulations related to the urban space will be. We describe our approach to develop the geometric layer of the digital twin of the city of Matera, in Italy, using only pre-existing public data. Specifically, our method exploits available digital elevation models from a previous regional aerial survey and integrates them with data coming from OpenStreetMap to generate an as-precise-as-possible 3D model, annotated with heterogeneous semantic information. We demonstrate the potential of the geometric layer by developing two geometric characterisation services, namely route slope extraction and light/shadow maps according to a specific date and time. In the next steps, the computed attributes will help to answer specific objectives which could be of interest for the Municipality, such as personalised optimal routes taking into account user preferences including slope and perceived environmental comfort.
Susceptibility Mapping of Typical Geological Hazards in Helong City Affected by Volcanic Activity of Changbai Mountain, Northeastern China
Authors: Sun Xiaohui , Yu Chenglong , Li Yanrong , Rene Ngambua N.
Published: June 2022

The purpose of this paper was to produce the geological hazard-susceptibility map for the Changbai Mountain area affected by volcanic activity. First, 159 landslides and 72 debris flows were mapped in the Helong city are based on the geological disaster investigation and regionalization (1:50,000) project of Helong City. Then, twelve landslide conditioning factors and eleven debris flow conditioning factors were selected as the modeling variables. Among them, the transcendental probability of Changbai Mountain volcanic earthquake greater than VI degrees was used to indicate the relationship between the geological hazard-susceptibility and Changbai Mountain volcanic earthquake occurrence. Furthermore, two machine learning models (SVM and ANN) were introduced to geological hazard-susceptibility modeling. Receiver operating characteristic curve, statistical analysis method, and five-fold cross-validation were used to compare the two models. Based on the modeling results, the SVM model is the better model for both the landslide and debris flow susceptibility mapping. The results show that the areas with low, moderate, high, and very high landslide susceptibility are 31.58%, 33.15%, 17.07%, and 18.19%, respectively; and the areas with low, moderate, high, and very high debris flow susceptibility are 25.63%, 38.19%, 23.47%, and 12.71%, respectively. The high and very high landslide and debris flow susceptibility classes make up 85.54% and 80.55% of the known landslides and debris flow, respectively. Moreover, the very high and high landslide and debris flow susceptibility are mainly distributed in the lower elevation area, and mainly distributed around the cities and towns in Helong City. Consequently, this paper will be a useful guide for the deployment of disaster prevention and mitigation in Helong city, and can also provide some reference for evaluation of landslide susceptibility in other volcanically active areas.
Dual-Hit Model of Parkinson’s Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice—Neuroprotective and Anti-Inflammatory Effects of Butyrate
Authors: Avagliano Carmen , Coretti Lorena , Lama Adriano , Pirozzi Claudio , De Caro Carmen , De Biase Davide , Turco Luigia , Mollica Maria Pina , Paciello Orlando , Calignano Antonio , Meli Rosaria , Lembo Francesca , Mattace Raso Giuseppina
Published: June 2022

Recent evidence highlights Parkinson’s disease (PD) initiation in the gut as the prodromal phase of neurodegeneration. Gut impairment due to microbial dysbiosis could affect PD pathogenesis and progression. Here, we propose a two-hit model of PD through ceftriaxone (CFX)-induced dysbiosis and gut inflammation before the 6-hydroxydopamine (6-OHDA) intrastriatal injection to mimic dysfunctional gut-associated mechanisms preceding PD onset. Therefore, we showed that dysbiosis and gut damage amplified PD progression, worsening motor deficits induced by 6-OHDA up to 14 days post intrastriatal injection. This effect was accompanied by a significant increase in neuronal dopaminergic loss (reduced tyrosine hydroxylase expression and increased Bcl-2/Bax ratio). Notably, CFX pretreatment also enhanced systemic and colon inflammation of dual-hit subjected mice. The exacerbated inflammatory response ran in tandem with a worsening of colonic architecture and gut microbiota perturbation. Finally, we demonstrated the beneficial effect of post-biotic sodium butyrate in limiting at once motor deficits, neuroinflammation, and colon damage and re-shaping microbiota composition in this novel dual-hit model of PD. Taken together, the bidirectional communication of the microbiota–gut–brain axis and the recapitulation of PD prodromal/pathogenic features make this new paradigm a useful tool for testing or repurposing new multi-target compounds in the treatment of PD.
Metabolomic Profiling of Angiotensin-II-Induced Abdominal Aortic Aneurysm in Ldlr−/− Mice Points to Alteration of Nitric Oxide, Lipid, and Energy Metabolisms
Authors: Chao de la Barca Juan Manuel , Richard Alexis , Robert Pauline , Eid Maroua , Fouquet Olivier , Tessier Lydie , Wetterwald Céline , Faure Justine , Fassot Celine , Henrion Daniel , Reynier Pascal , Loufrani Laurent
Published: June 2022

Aneurysm is the second-most common disease affecting the aorta worldwide after atherosclerosis. While several clinical metabolomic studies have been reported, no study has reported deep metabolomic phenotyping in experimental animal models of aortic aneurysm. We performed a targeted metabolomics study on the blood and aortas of an experimental mice model of aortic aneurysm generated by high-cholesterol diet and angiotensin II in Ldlr−/− mice. The mice model showed a significant increase in media/lumen ratio and wall area, which is associated with lipid deposition within the adventitia, describing a hypertrophic remodeling with an aneurysm profile of the abdominal aorta. Altered aortas showed increased collagen remodeling, disruption of lipid metabolism, decreased glucose, nitric oxide and lysine metabolisms, and increased polyamines and asymmetric dimethylarginine (ADMA) production. In blood, a major hyperlipidemia was observed with decreased concentrations of glutamine, glycine, taurine, and carnitine, and increased concentrations of the branched amino acids (BCAA). The BCAA/glycine and BCAA/glutamine ratios discriminated with very good sensitivity and specificity between aneurysmatic and non-aneurysmatic mice. To conclude, our results reveal that experimental induction of aortic aneurysms causes a profound alteration in the metabolic profile in aortas and blood, mainly centered on an alteration of NO, lipid, and energetic metabolisms.
The Treatment of Advanced Melanoma: Therapeutic Update
Authors: Villani Alessia , Potestio Luca , Fabbrocini Gabriella , Troncone Giancarlo , Malapelle Umberto , Scalvenzi Massimiliano
Published: June 2022

Cutaneous melanoma is the main cause of death for skin cancer. The majority of patients with a diagnosis of melanoma have localized disease, which can be successfully treated with surgical treatment. However, the surgical approach is not curative for advanced melanoma (AM). Indeed, the management of AM is still challenging, since melanoma is the solid tumor with the highest number of mutations and cancer cells have the capacity to evade the immune system. In the past, the treatment of AM relied on chemotherapeutic agents, without showing efficacy data. Recent knowledge on melanoma pathogenesis as well as the introduction of immunotherapies, targeted therapies vaccines, small molecules, and combination therapies has revolutionized AM management, showing promising results in terms of effectiveness and safety. The aim of this review is to assess and to discuss the role of emerging therapies for AM management in order to obtain a complete overview of the currently available treatment options and future perspectives.
Transcriptome and Metabolome Analysis Provide New Insights into the Process of Tuberization of Sechium edule Roots
Authors: Su Lihong , Cheng Shaobo , Liu Yuhang , Xie Yongdong , He Zhongqun , Jia Mingyue , Zhou Xiaoting , Zhang Ruijie , Li Chunyan
Published: June 2022

Chayote (Sechium edule) produces edible tubers with high starch content after 1 year of growth but the mechanism of chayote tuberization remains unknown. ‘Tuershao’, a chayote cultivar lacking edible fruits but showing higher tuber yield than traditional chayote cultivars, was used to study tuber formation through integrative analysis of the metabolome and transcriptome profiles at three tuber-growth stages. Starch biosynthesis- and galactose metabolism-related genes and metabolites were significantly upregulated during tuber bulking, whereas genes encoding sugars will eventually be exported transporter (SWEET) and sugar transporter (SUT) were highly expressed during tuber formation. Auxin precursor (indole-3-acetamide) and ethylene precursor, 1-aminocyclopropane-1-carboxylic acid, were upregulated, suggesting that both hormones play pivotal roles in tuber development and maturation. Our data revealed a similar tuber-formation signaling pathway in chayote as in potatoes, including complexes BEL1/KNOX and SP6A/14-3-3/FDL. Down-regulation of the BEL1/KNOX complex and upregulation of 14-3-3 protein implied that these two complexes might have distinct functions in tuber formation. Finally, gene expression and microscopic analysis indicated active cell division during the initial stages of tuber formation. Altogether, the integration of transcriptome and metabolome analyses unraveled an overall molecular network of chayote tuberization that might facilitate its utilization.
Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins
Authors: Troyano-Hernáez Paloma , Reinosa Roberto , Holguín África
Published: June 2022

Monitoring SARS-CoV-2’s genetic diversity and emerging mutations in this ongoing pandemic is crucial to understanding its evolution and ensuring the performance of COVID-19 diagnostic tests, vaccines, and therapies. Spain has been one of the main epicenters of COVID-19, reaching the highest number of cases and deaths per 100,000 population in Europe at the beginning of the pandemic. This study aims to investigate the epidemiology of SARS-CoV-2 in Spain and its 18 Autonomous Communities across the six epidemic waves established from February 2020 to January 2022. We report on the circulating SARS-CoV-2 variants in each epidemic wave and Spanish region and analyze the mutation frequency, amino acid (aa) conservation, and most frequent aa changes across each structural/non-structural/accessory viral protein among the Spanish sequences deposited in the GISAID database during the study period. The overall SARS-CoV-2 mutation frequency was 1.24 × 10−5. The aa conservation was >99% in the three types of protein, being non-structural the most conserved. Accessory proteins had more variable positions, while structural proteins presented more aa changes per sequence. Six main lineages spread successfully in Spain from 2020 to 2022. The presented data provide an insight into the SARS-CoV-2 circulation and genetic variability in Spain during the first two years of the pandemic.
Aryl Hydrocarbon Receptor Promotes Cell Growth, Stemness Like Characteristics, and Metastasis in Human Ovarian Cancer via Activation of PI3K/Akt, β-Catenin, and Epithelial to Mesenchymal Transition Pathways
Authors: Therachiyil Lubna , Krishnankutty Roopesh , Ahmad Fareed , Mateo Jericha M. , Uddin Shahab , Korashy Hesham M.
Published: June 2022

Ovarian cancer (OC) ranks first in cancer-related deaths out of all female reproductive malignancies with high-pitched tumor relapse and chemoresistance. Several reports correlate cancer occurrences with exposure to xenobiotics via induction of a protein receptor named aryl hydrocarbon receptor (AhR). However, the effect of AhR on OC proliferation, expansion, and chemoresistance remains unrevealed. For this purpose, OC cells A2780 and A2780cis cells were treated with AhR activator, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the effects were determined by Real-Time Cell Analyzer, clonogenic assay, flow cytometry, immunoblotting and wound healing assay. Our results showed that activation of AhR by TCDD in A2780 cells induced the PI3K/AKT pathway followed by induction of anti-apoptotic proteins BCL-2, BCL-xl, and MCL-1. In addition, a significant increase in stemness marker aldehyde dehydrogenase (ALDH1) was observed. This effect was also associated with an accumulation of β-catenin, a Wnt transcription factor. Moreover, we observed induction of epithelial to mesenchymal transition (EMT) upon AhR activation. In conclusion, the results from the current study confirm that AhR mediates OC progression, stemness characteristics, and metastatic potential via activation of PI3K/Akt, Wnt/β-catenin, and EMT. This study provides a better insight into the modulatory role of AhR that might help in developing novel therapeutic strategies for OC treatment.
The Role of Polyphenol in Modulating Associated Genes in Diabetes-Induced Vascular Disorders
Authors: Mohd Nor Nor Anizah , Budin Siti Balkis , Zainalabidin Satirah , Jalil Juriyati , Sapian Syaifuzah , Jubaidi Fatin Farhana , Mohamad Anuar Nur Najmi
Published: June 2022

Diabetes-induced vascular disorder is considered one of the deadly risk factors among diabetic patients that are caused by persistent hyperglycemia that eventually leads to cardiovascular diseases. Elevated reactive oxygen species (ROS) due to high blood glucose levels activate signaling pathways such as AGE/RAGE, PKC, polyol, and hexosamine pathways. The activated signaling pathway triggers oxidative stress, inflammation, and apoptosis which later lead to vascular dysfunction induced by diabetes. Polyphenol is a bioactive compound that can be found abundantly in plants such as vegetables, fruits, whole grains, and nuts. This compound exerts therapeutic effects in alleviating diabetes-induced vascular disorder, mainly due to its potential as an anti-oxidative, anti-inflammatory, and anti-apoptotic agent. In this review, we sought to summarize the recent discovery of polyphenol treatments in modulating associated genes involved in the progression of diabetes-induced vascular disorder.
Melanoma Cellular Plasticity
Authors: Novak Daniel , Utikal Jochen
Published: June 2022

Despite the advances of modern medicine and the development of innovative and promising new therapeutic strategies for the treatment of the numerous types of cancer, far too many patients still lose the battle against these devastating diseases [...]
Advances in Endothelial Cell Biology: From Knowledge to Control
Authors: Charreau Béatrice
Published: June 2022

The aim of this Special Issue is to provide an overview of recent investigations in the field of endothelial cell (EC) biology that advance our understanding of the molecular mechanisms that trigger normal EC functions and dysfunctions in pathologies and to demonstrate how improved knowledge of EC biology may lead to the discovery of novel molecular diagnostic technologies and targeted therapeutics [...]
Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet
Authors: Zaloszyc Ariane , Choquet Philippe , Sayeh Amira , Bartosova Maria , Schaefer Betti , Huegel Ulrike , Aubertin-Kirch Gaëlle , Healy Christopher , Severac François , Rizzo Sébastien , Boivin Georges , Schaefer Franz , Fischbach Michel , Bacchetta Justine , Bahram Seiamak , Schmitt Claus Peter
Published: June 2022

Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease.
Stepwise Proliferation and Chondrogenic Differentiation of Mesenchymal Stem Cells in Collagen Sponges under Different Microenvironments
Authors: Zheng Jing , Xie Yan , Yoshitomi Toru , Kawazoe Naoki , Yang Yingnan , Chen Guoping
Published: June 2022

Biomimetic microenvironments are important for controlling stem cell functions. In this study, different microenvironmental conditions were investigated for the stepwise control of proliferation and chondrogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs). The hMSCs were first cultured in collagen porous sponges and then embedded with or without collagen hydrogels for continual culture under different culture conditions. The different influences of collagen sponges, collagen hydrogels, and induction factors were investigated. The collagen sponges were beneficial for cell proliferation. The collagen sponges also promoted chondrogenic differentiation during culture in chondrogenic medium, which was superior to the effect of collagen sponges embedded with hydrogels without loading of induction factors. However, collagen sponges embedded with collagen hydrogels and loaded with induction factors had the same level of promotive effect on chondrogenic differentiation as collagen sponges during in vitro culture in chondrogenic medium and showed the highest promotive effect during in vivo subcutaneous implantation. The combination of collagen sponges with collagen hydrogels and induction factors could provide a platform for cell proliferation at an early stage and subsequent chondrogenic differentiation at a late stage. The results provide useful information for the chondrogenic differentiation of stem cells and cartilage tissue engineering.
Proteome of Staphylococcus aureus Biofilm Changes Significantly with Aging
Authors: Rahman Md. Arifur , Amirkhani Ardeshir , Chowdhury Durdana , Mempin Maria , Molloy Mark P. , Deva Anand Kumar , Vickery Karen , Hu Honghua
Published: June 2022

Staphylococcus aureus is a notorious biofilm-producing pathogen that is frequently isolated from implantable medical device infections. As biofilm ages, it becomes more tolerant to antimicrobial treatment leading to treatment failure and necessitating the costly removal of infected devices. In this study, we performed in-solution digestion followed by TMT-based high-throughput mass spectrometry and investigated what changes occur in the proteome of S. aureus biofilm grown for 3-days and 12-days in comparison with 24 h planktonic. It showed that proteins associated with biosynthetic processes, ABC transporter pathway, virulence proteins, and shikimate kinase pathway were significantly upregulated in a 3-day biofilm, while proteins associated with sugar transporter, degradation, and stress response were downregulated. Interestingly, in a 3-day biofilm, we observed numerous proteins involved in the central metabolism pathways which could lead to biofilm growth under diverse environments by providing an alternative metabolic route to utilize energy. In 12-day biofilms, proteins associated with peptidoglycan biosynthesis, sugar transporters, and stress responses were upregulated, whereas proteins associated with ABC transporters, DNA replication, and adhesion proteins were downregulated. Gene Ontology analysis revealed that more proteins are involved in metabolic processes in 3dwb compared with 12dwb. Furthermore, we observed significant variations in the formation of biofilms resulting from changes in the level of metabolic activity in the different growth modes of biofilms that could be a significant factor in S. aureus biofilm maturation and persistence. Collectively, potential marker proteins were identified and further characterized to understand their exact role in S. aureus biofilm development, which may shed light on possible new therapeutic regimes in the treatment of biofilm-related implant-associated infections.
A Type Ib Crustin from Deep-Sea Shrimp Possesses Antimicrobial and Immunomodulatory Activity
Authors: Wang Yu-Jian , Sun Li
Published: June 2022

Crustins are small antimicrobial proteins produced by crustaceans. Of the many reported crustins, very few are from deep sea environments. Crustins are categorized into several types. Recently, the Type I crustin has been further classified into three subtypes, one of which is Type Ib, whose function is unknown. Here, we studied the function of a Type Ib crustin (designated Crus2) identified from a deep-sea crustacean. Crus2 has a whey acidic protein (WAP) domain and a long C-terminal region (named P58). Recombinant Crus2 bound to peptidoglycan (PGN), lipoteichoic acid (LTA), and lipopolysaccharide (LPS), and killed Gram-positive and Gram-negative bacteria by permeabilizing the bacterial cytomembrane. Consistently, Crus2 dramatically attenuated the inflammatory response induced by LPS and LTA. Disruption of the disulfide bonds in the WAP domain abolished the bactericidal ability of Crus2, but had no effect on the bacterial binding ability of Crus2. Deletion of the C-terminal P58 region moderately affected the antimicrobial activity of Crus2 against some bacteria. P58 as a synthesized peptide could bind bacteria and inhibit the bactericidal activity of Crus2. Taken together, these results revealed different roles played by the WAP domain and the P58 region in Type Ib crustin, and provided new insights into the antimicrobial and immunomodulatory functions of crustins.
Immunity, Ion Channels and Epilepsy
Authors: Chen Tsang-Shan , Lai Ming-Chi , Huang Huai-Ying Ingrid , Wu Sheng-Nan , Huang Chin-Wei
Published: June 2022

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise.
The Identification of Broomcorn Millet bZIP Transcription Factors, Which Regulate Growth and Development to Enhance Stress Tolerance and Seed Germination
Authors: An Peipei , Li Xiang , Liu Tianxiang , Shui Zhijie , Chen Mingxun , Gao Xin , Wang Zhonghua
Published: June 2022

Broomcorn millet (Panicum miliaceum L.) is a water-efficient and highly salt-tolerant plant. In this study, the salt tolerance of 17 local species of broomcorn millet was evaluated through testing based on the analysis of the whitening time and the germination rate of their seeds. Transcriptome sequencing revealed that PmbZIP131, PmbZIP125, PmbZIP33, PmABI5, PmbZIP118, and PmbZIP97 are involved in seed germination under salt stress. Seedling stage expression analysis indicates that PmABI5 expression was induced by treatments of high salt (200 mM NaCl), drought (20% W/V PEG6000), and low temperature (4 °C) in seedlings of the salt-tolerant variety Y9. The overexpression of PmABI5 significantly increases the germination rate and root traits of Arabidopsis thaliana transgenic lines, with root growth and grain traits significantly enhanced compared to the wild type (Nipponbare). BiFC showed that PmABI5 undergoes homologous dimerization in addition to forming a heterodimer with either PmbZIP33 or PmbZIP131. Further yeast one-hybrid experiments showed that PmABI5 and PmbZIP131 regulate the expression of PmNAC1 by binding to the G-box in the promoter. These results indicate that PmABI5 can directly regulate seed germination and seedling growth and indirectly improve the salt tolerance of plants by regulating the expression of the PmNAC1 gene through the formation of heterodimers with PmbZIP131.
Exploring the Origin and Physiological Significance of DNA Double Strand Breaks in the Developing Neuroretina
Authors: Álvarez-Lindo Noemí , Suárez Teresa , de la Rosa Enrique J.
Published: June 2022

Genetic mosaicism is an intriguing physiological feature of the mammalian brain that generates altered genetic information and provides cellular, and prospectively functional, diversity in a manner similar to that of the immune system. However, both its origin and its physiological significance remain poorly characterized. Most, if not all, cases of somatic mosaicism require prior generation and repair of DNA double strand breaks (DSBs). The relationship between DSB generation, neurogenesis, and early neuronal cell death revealed by our studies in the developing retina provides new perspectives on the different mechanisms that contribute to DNA rearrangements in the developing brain. Here, we speculate on the physiological significance of these findings.
The m6A Methyltransferase METTL3-Mediated N6-Methyladenosine Modification of DEK mRNA to Promote Gastric Cancer Cell Growth and Metastasis
Authors: Zhang Hui-Min , Qi Fei-Fei , Wang Jun , Duan Yuan-Yuan , Zhao Li-Li , Wang Yun-Dan , Zhang Tong-Cun , Liao Xing-Hua
Published: June 2022

Gastric cancer (GC) is the fifth most common cancer and the third deadliest cancer in the world, and the occurrence and development of GC are influenced by epigenetics. Methyltransferase-like 3 (METTL3) is a prominent RNA n6-adenosine methyltransferase (m6A) that plays an important role in tumor growth by controlling the work of RNA. This study aimed to reveal the biological function and molecular mechanism of METTL3 in GC. The expression level of METTL3 in GC tissues and cells was detected by qPCR, Western blot and immunohistochemistry, and the expression level and prognosis of METTL3 were predicted in public databases. CCK-8, colony formation, transwell and wound healing assays were used to study the effect of METTL3 on GC cell proliferation and migration. In addition, the enrichment effect of METTL3 on DEK mRNA was detected by the RIP experiment, the m6A modification effect of METTL3 on DEK was verified by the MeRIP experiment and the mRNA half-life of DEK when METTL3 was overexpressed was detected. The dot blot assay detects m6A modification at the mRNA level. The effect of METTL3 on cell migration ability in vivo was examined by tail vein injection of luciferase-labeled cells. The experimental results showed that METTL3 was highly expressed in GC tissues and cells, and the high expression of METTL3 was associated with a poor prognosis. In addition, the m6A modification level of mRNA was higher in GC tissues and GC cell lines. Overexpression of METTL3 in MGC80-3 cells and AGS promoted cell proliferation and migration, while the knockdown of METTL3 inhibited cell proliferation and migration. The results of in vitro rescue experiments showed that the knockdown of DEK reversed the promoting effects of METTL3 on cell proliferation and migration. In vivo experiments showed that the knockdown of DEK reversed the increase in lung metastases caused by the overexpression of METTL3 in mice. Mechanistically, the results of the RIP experiment showed that METTL3 could enrich DEK mRNA, and the results of the MePIP and RNA half-life experiments indicated that METTL3 binds to the 3’UTR of DEK, participates in the m6A modification of DEK and promotes the stability of DEK mRNA. Ultimately, we concluded that METTL3 promotes GC cell proliferation and migration by stabilizing DEK mRNA expression. Therefore, METTL3 is a potential biomarker for GC prognosis and a therapeutic target.