bluuebunny/crossref_metadata_2025 huggingface dataset:
A Conceptual Model of Nurses’ Turnover Intention
Authors: Smokrović Eva , Kizivat Tomislav , Bajan Antun , Šolić Krešimir , Gvozdanović Zvjezdana , Farčić Nikolina , Žvanut Boštjan
Published: July 2022

The World Health Organisation predicts a lack of 15 million health professionals by 2030. The lack of licenced professionals is a problem that keeps emerging and is carefully studied on a global level. Strategic objectives aimed at stimulating employment, improving working conditions, and keeping the nurses on board greatly depends on identifying factors that contribute to their turnover. The aim of this study was to present a conceptual model based on predictors of nurses’ turnover intention. Methods: A quantitative, non-experimental research design was used. A total of 308 registered nurses (RNs) took part in the study. The Multidimensional Work Motivation Scale (MWMS) and Practice Environment Scale of the Nursing Work Index (PES-NWI) were used. Results: The conceptual model, based on the binary regression models, relies on two direct significant predictors and four indirect significant predictors of turnover intention. The direct predictors are job satisfaction (OR = 0.23) and absenteeism (OR = 2.5). Indirect predictors that affect turnover intention via job satisfaction are: amotivation (OR = 0.59), identified regulation (OR = 0.54), intrinsic motivation (OR = 1.67), and nurse manager ability, leadership and support of nurses (OR = 1.51). Conclusions: The results of the study indicate strategic issues that need to be addressed to retain the nursing workforce. There is a need to ensure positive perceptions and support from managers, maintain intrinsic motivation, and promote even higher levels of motivation to achieve satisfactory levels of job satisfaction.
Stress Increases the Association between Cigarette Smoking and Mental Disorders, as Measured by the COVID-19-Related Worry Scale, in the Miami Adult Studies on HIV (MASH) Cohort during the Pandemic
Authors: Diaz-Martinez Janet , Delgado-Enciso Ivan , Campa Adriana , Tamargo Javier A. , Martin Haley R. , Johnson Angelique , Siminski Suzanne , Gorbach Pamina M. , Baum Marianna K.
Published: July 2022

Background: Smoking has been associated with mental disorders (MD). People who smoke are at a higher risk of contracting COVID-19 and experiencing more severe symptoms of the illness. This study aimed to investigate the relationship between cigarette smoking and MD before and during the COVID-19 pandemic and whether it was influenced by COVID-19-related stress in the MASH cohort. Methods: An ambispective design was used with data collected during the pandemic (July/August 2020) by the COVID-19-Related Worry Scale, a parameter for stress, and data collected at the participants’ last cohort visit before the pandemic (December 2019). Results: In our sample of 314 participants, 58.6% were living with HIV, 39.2% had MD, 52.5% smoked before, and 47.8% smoked during the pandemic. Participants with MD were twice as likely to smoke cigarettes both before (aOR = 2.02, 95% CI: 1.21–3.37, p = 0.007) and during the pandemic (aOR = 2.10, 95% CI: 1.24–3.56, p = 0.006); and experienced higher levels of stress measured by the COVID-19-Related Worry Scale (8.59 [5.0–10.0] vs. 7.65 [5.0–10.0]; p = 0.026) compared to those without MD. Participants with MD and high levels of stress smoked more days per month (20.1 [0–30] days) than those with lower levels of stress (9.2 [0–30] days, p = 0.021), and more than those with high levels of stress, but no MD (2.6 [0–30] days, p < 0.001). Conclusions: Cigarette smoking decreased in the MASH cohort during the pandemic, but increased in participants with MD and higher levels of stress.
Effects of Blended Learning Program for Cyber Sexual Harassment Prevention among Female High School Students in Bangkok, Thailand
Authors: Santre Siriporn , Pumpaibool Tepanata
Published: July 2022

Cyber sexual harassment has been increasing and has become a major public health problem among youths. Therefore, this study primarily aimed to evaluate the effects of a blended learning program on knowledge, attitudes, intention to cope with cyber sexual harassment, behavioral coping strategies, and cyber sexual harassment among female high-school students in Bangkok, Thailand. A quasi-experimental study with a two-group design was conducted from May 2021 to October 2021. A total of 112 students were recruited into either an intervention (n = 56) or a control (n = 56) group. The intervention group participated in a blended learning program for 12 weeks. A self-administered questionnaire was completed by both groups at pre-intervention, post-intervention, and follow-up. Chi-square test, Fisher’s exact test, and repeated measures analysis of variance (ANOVA) were used for data analysis. The mean score of the intervention group in knowledge, attitude, intention to cope with cyber sexual harassment, behavioral coping strategies, and cyber sexual harassment after completing the program and follow-up were significantly different from baseline and the control group (p < 0.05). A positive effect of the blended learning program was observed among female students. Therefore, this program can be useful for victims, supporting their self-confidence with decreased frequency of cyber sexual harassment experiences.
Metformin and the Development of Asthma in Patients with Type 2 Diabetes
Authors: Yen Fu-Shun , Hsu Chih-Cheng , Shih Ying-Hsiu , Pan Wei-Lin , Wei James Cheng-Chung , Hwu Chii-Min
Published: July 2022

We conducted this study to compare the risks of asthma development and exacerbation between metformin users and nonusers. Overall, 57,743 propensity score-matched metformin users and nonusers were identified from Taiwan’s National Health Insurance Research Database between 1 January 2000, and 31 December 2017. We used the Cox proportional hazards model with robust standard error estimates to compare the risks of asthma onset, exacerbation, and hospitalization for asthma in participants with type 2 diabetes (T2D). Compared with metformin nonuse, the aHRs (95% CI) for metformin use in asthma development, exacerbation, and hospitalization for asthma were 1.13 (1.06–1.2), 1.62 (1.35–1.95), and 1.5 (1.22–1.85), respectively. The cumulative incidences of asthma development, exacerbation, and hospitalization for asthma were significantly higher in metformin users than nonusers (p < 0.001). A longer cumulative duration of metformin use for more than 728 days was associated with significantly higher risks of outcomes than metformin nonuse. Our study demonstrated that metformin users showed significantly higher risks of asthma development, exacerbation, and hospitalization for asthma than metformin nonusers. Moreover, metformin use for more than 728 days was associated with higher risks of outcomes. A randomized control study is warranted to verify our results.
Efficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis
Authors: Wang Haolin , Huang Wendy Y. , Zhao Yanan
Published: July 2022

This study aimed to analyze the efficacy of exercise interventions on muscle strength, muscle mass, and physical performance in older adults with sarcopenia. Randomized controlled studies assessing exercise effects on sarcopenia were searched in Web of Science, PubMed, Cochrane Library, ProQuest, EBSCOhost, Scopus, EMBASE, and VIP and CNKI up to 31 March 2022. Data were expressed as weighted/standardized mean difference (MD/SMD) with 95% confidence intervals (CI). I2 index was employed for heterogeneity. The initial search identified 5379 studies, and 23 studies involving 1252 participants met the inclusion criteria for further analysis. Results revealed that exercise interventions can significantly improve grip strength (MD = 2.38, 95%CI = 1.33–3.43), knee extension strength (SMD = 0.50, 95%CI = 0.36–0.64), muscle mass of lower extremities (MD = 0.28, 95%CI = 0.01–0.56), walking speed (SMD = 0.88, 95%CI = 0.49–1.27), and functional mobility (MD = −1.77, 95%CI = −2.11–−1.42) among older adults with sarcopenia. No significant exercise effects were found on fat-free muscle mass, appendicular muscle mass, skeletal muscle mass, and muscle mass of the upper extremities. The results of subgroup analysis indicated that both resistance training and multicomponent exercise could significantly increase the muscle strength, while aerobic exercise did not. The findings suggest that exercise intervention can effectively improve muscle function and physical performance in older adults with sarcopenia, but has limited effects on the muscle mass of the upper extremities. In addition, it is highly recommended to apply group-based and supervised resistance training and multicomponent exercise in the prevention and treatment of sarcopenia among the older population.
The Typology and Topography of Child Abuse and Neglect: The Experience of a Tertiary Children’s Centre
Authors: Debelle Geoff , Efstathiou Nikolaos , Khan Rafiyah , Williamson Annette , Summan Manjit , Taylor Julie
Published: July 2022

Effective child protection systems and processes require reliable and accurate data. The aim of this study was to determine what data could be extracted from hospital records in a single site that reflected a child’s journey from admission with suspected abuse to the decisions regarding substantiation made by the multidisciplinary child protection team. A retrospective study of the case records of 452 children referred to a major UK children’s tertiary centre for suspected child maltreatment was undertaken. Child maltreatment was substantiated in 65% of referred cases, with the majority of referrals coming from children living in the most deprived neighbourhoods in the country. Domestic violence and abuse and the child’s previous involvement with statutory bodies were associated with case substantiation. Physical abuse predominated, with soft tissue injuries, including dog bites and burns, most frequent. Burns were related almost exclusively to supervisory neglect. There were also cases of medical neglect. Emotional abuse was associated with exposure to domestic violence and abuse and to self-harm. The strengths and limitations for single-centre data systems were explored, concluding with a recommendation to establish an agreed national and international minimum data set to protect children from maltreatment.
A Complex Hybrid Model for Evaluating Projects to Improve the Sustainability and Health of Regions and Cities
Authors: Kelemen Miroslav , Gavurova Beata , Polishchuk Volodymyr
Published: July 2022

The main goal of the study is to develop a complex hybrid model for evaluating projects to improve the sustainability and health of regions and cities within the European Green Deal and Industry 5.0 concepts. The complex model is a comprehensive evaluation system that considers various influencing factors, the investor’s intentions regarding the need and financing of projects, as well as expert opinion on the possibility of achieving sustainability and health of regions and cities by implementing this project with the investor. The model is based on modern theory of intellectual knowledge analysis, fuzzy set theory, and systems approach. Furthermore, we have an initial quantitative assessment and the linguistic significance of the level of the project financing decision with a reliability assessment. The knowledge from the repository of 896 project plans in the field of transport submitted for implementation and financing in the period 2021–2027 was used for the creation of the model. The results of the study were tested on the examples of evaluation of five real projects and demonstrated the applied value of the methodology for evaluating the level of decision-making feasibility of project financing in uncertainty and the importance of making correct management decisions based on expert opinions.
Green Infrastructure and Urban-Renewal Simulation for Street Tree Design Decision-Making: Moderating Demands of Stormwater Management, Sunlight and Visual Aesthetics
Authors: Langenheim Nano , White Marcus
Published: July 2022

The design of green infrastructure in urban renewal sites is complex, requiring engagement with existing communities and future sustainable development goals, consideration of existing and future urban forms, changing climatic conditions, and the sites often being in low-lying and flood-prone areas. Traditional street tree decision-making approaches are inadequate for addressing the scale, environmental complexity, and mutability of decisions involved in urban renewal projects—new tree selection approaches that consider complex competing criteria for tree selections addressing stormwater management systems, visual assessment and solar amenity are needed. This paper describes a new method of multi-criteria street design decision modelling that combines outputs from hydrology modelling, digital procedural tree modelling and urban form analysis, with animation and gaming technologies. We evaluate our approach through application to the design of a large-scale, urban renewal project underway in Melbourne, Australia. The results of the study demonstrate the functionality of our model, which allowed the simultaneous output of streetscape visualisation, with tree selection responding to integrated stormwater management infrastructure and flooding, along with the likely overshadowing conditions of urban renewal built-form. Our multi-criteria approach makes a significant contribution to the tools available to urban designers, planners and landscape architects in their pursuit of smarter streetscape design decisions that respond to complex spatial, cultural and climatic urban challenges.
Regional Trends and Socioeconomic Predictors of Adolescent Pregnancy in Nigeria: A Nationwide Study
Authors: Akombi-Inyang Blessing Jaka , Woolley Emma , Iheanacho Chinonyerem Ogadi , Bayaraa Khulan , Ghimire Pramesh Raj
Published: July 2022

Adolescent pregnancy is a major health concern which has lifelong consequences. The aim of this study is to examine the regional trends and socioeconomic predictors of adolescent pregnancy in Nigeria. This study used pooled data from the 2008, 2013 and 2018 Nigeria Demographic and Health Survey (NDHS). A total of 22,761 women aged 15–19 years were selected across the three surveys. Multilevel logistic regression analysis that adjusted for cluster and survey weights was used to identify predictors of adolescent pregnancy in Nigeria, across the six geopolitical zones of Nigeria. Adolescent pregnancy remained constant between 2008 (22.9%; 95% CI = 22.14, 24.66), and 2013 (22.5%; 95% CI = 20.58, 24.50), but a significant decline was reported in 2018 (18.7%; 95% CI = 17.12, 20.46). Trends show a decrease in adolescent pregnancy across all six geopolitical zones, except for the South-East zone which reported a slight increase (0.6%). Multivariable analysis revealed that the main socioeconomic predictors across all six geopolitical zones were: poor households, increasing age, and low education. Exposure to media (watching television and reading newspapers) was reported as predictor in all regions except the North-East geopolitical zone, while all northern zones reported high levels of adolescent pregnancy in male-led households. To address adolescent pregnancy in Nigeria, there is need to promote girls’ education especially among poor households, and for the dissemination of reproductive health messages to adolescents through various forms of mass media campaign, as well as the adoption of social marketing interventions to improve sexual and reproductive health literacy.
Target of Rapamycin Signaling Involved in the Regulation of Photosynthesis and Cellular Metabolism in Chlorella sorokiniana
Authors: Li Linxuan , Zhu Tingting , Huang Lele , Ren Maozhi
Published: July 2022

Target of rapamycin (TOR) is a serine/threonine protein kinase that plays a central regulating role in cell proliferation, growth, and metabolism, but little is known about the TOR signaling pathway in Chlorella sorokiniana. In this study, a Chlorella sorokiniana DP-1 strain was isolated and identified, and its nutritional compositions were analyzed. Based on homologous sequence analysis, the conserved CsTOR protein was found in the genome of Chlorella sorokiniana. In addition, the key components of TOR complex 1 (TORC1) were present, but the components of TORC2 (RICTOR and SIN1) were absent in Chlorella sorokiniana. Pharmacological assays showed that Chlorella sorokiniana DP-1 was insensitive to rapamycin, Torin1 and KU0063794, whereas AZD8055 could significantly inhibit the growth of Chlorella sorokiniana. RNA-seq analysis showed that CsTOR regulated various metabolic processes and signal transduction pathways in AZD8055-treated Chlorella sorokiniana DP-1. Most genes involved in photosynthesis and carbon fixation in Chlorella sorokiniana DP-1 were significantly downregulated under CsTOR inhibition, indicating that CsTOR positively regulated the photosynthesis in Chlorella sorokiniana. Furthermore, CsTOR controlled protein synthesis and degradation by positively regulating ribosome synthesis and negatively regulating autophagy. These observations suggested that CsTOR plays an important role in photosynthesis and cellular metabolism, and provide new insights into the function of CsTOR in Chlorella sorokiniana.
Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
Authors: Magkrioti Christiana , Antonopoulou Georgia , Fanidis Dionysios , Pliaka Vaia , Sakellaropoulos Theodore , Alexopoulos Leonidas G. , Ullmer Christoph , Aidinis Vassilis
Published: July 2022

Chronic kidney disease (CKD) refers to a spectrum of diseases defined by renal fibrosis, permanent alterations in kidney structure, and low glomerular-filtration rate. Prolonged epithelial-tubular damage involves a series of changes that eventually lead to CKD, highlighting the importance of tubular epithelial cells in this process. Lysophosphatidic acid (LPA) is a bioactive lipid that signals mainly through its six cognate LPA receptors and is implicated in several chronic inflammatory pathological conditions. In this report, we have stimulated human proximal tubular epithelial cells (HKC-8) with LPA and 175 other possibly pathological stimuli, and simultaneously detected the levels of 27 intracellular phosphoproteins and 32 extracellular secreted molecules with multiplex ELISA. This quantification revealed a large amount of information concerning the signaling and the physiology of HKC-8 cells that can be extrapolated to other proximal tubular epithelial cells. LPA responses clustered with pro-inflammatory stimuli such as TNF and IL-1, promoting the phosphorylation of important inflammatory signaling hubs, including CREB1, ERK1, JUN, IκΒα, and MEK1, as well as the secretion of inflammatory factors of clinical relevance, including CCL2, CCL3, CXCL10, ICAM1, IL-6, and IL-8, most of them shown for the first time in proximal tubular epithelial cells. The identified LPA-induced signal-transduction pathways, which were pharmacologically validated, and the secretion of the inflammatory factors offer novel insights into the possible role of LPA in CKD pathogenesis.
Plocabulin, a Novel Tubulin Inhibitor, Has Potent Antitumour Activity in Patient-Derived Xenograft Models of Soft Tissue Sarcoma
Authors: Wang Yannick , Wozniak Agnieszka , Cornillie Jasmien , Avilés Pablo , Debiec-Rychter Maria , Sciot Raf , Schöffski Patrick
Published: July 2022

A clinically relevant subset of patients with soft tissue sarcoma presents with either locally advanced or upfront metastatic disease, or will develop distant metastases over time, despite successful treatment of their primary tumour. The currently available systemic agents to treat such advanced cases only provide modest disease control and are not active in all histological subtypes. Thus, there is an unmet need for novel and more efficacious agents to improve the outcome of this rare disease. In the current preclinical in vivo study, we evaluated plocabulin, a novel tubulin inhibitor, in five distinct histological subtypes of soft tissue sarcoma: dedifferentiated liposarcoma, leiomyosarcoma, undifferentiated sarcoma, intimal sarcoma and CIC-rearranged sarcoma. The efficacy was tested in seven patient-derived xenograft models, which were generated by the engraftment of tumour fragments from patients directly into nude mice. The treatment lasted 22 days, and the efficacy of the drug was assessed and compared to the doxorubicin and vehicle groups by volumetric analysis, histopathology and immunohistochemistry. We observed tumour volume control in all the tested histological subtypes. Additionally, in three sarcoma subtypes, extensive central necrosis, associated with significant tumour regression, was seen. This histological response is explained by the drug’s vascular-disruptive properties, reflected by a decreased total vascular area in the xenografts. Our results demonstrate the in vivo efficacy of plocabulin in the preclinical models of soft tissue sarcoma and corroborate the findings of our previous study, which demonstrated similar vascular-disruptive effects in gastrointestinal stromal tumours—another subtype of soft tissue sarcoma. Our data provide a convincing rationale for further clinical exploration of plocabulin in soft tissue sarcomas.
SDG102, a H3K36-Methyltransferase-Encoding Gene, Plays Pleiotropic Roles in Growth and Development of Maize (Zea mays L.)
Authors: Li Yongjian , Sun Weifeng , Wang Zhenhui , Wan Chang , Zhang Jun , Qi Xin , Zhang Jian
Published: July 2022

Although histone lysine methylation has been studied in thale cress (Arabidopsis thaliana (L.) Heynh.) and rice (Oryza sativa L.) in recent years, its function in maize (Zea mays L.) remains poorly characterized. To better understand the function of histone lysine methylation in maize, SDG102, a H3 lysine 36 (H3K36) methylase, was chosen for functional characterization using overexpressed and knockout transgenic plants. SDG102-deficiency in maize caused multiple phenotypes including yellow leaves in seedlings, late-flowering, and increased adult plant height, while the overexpression of SDG102 led to reduced adult plant height. The key flowering genes, ZCN8/ZCN7 and MADS4/MADA67, were downregulated in SDG102-deficient plants. Chromatin immunoprecipitation (ChIP) experiments showed that H3 lysine 36 trimethylation (H3K36me3) levels were reduced at these loci. Perturbation of SDG102 expression caused the misexpression of multiple genes. Interestingly, the overexpression or knockout of SDG102 also led to genome-wide decreases and increases in the H3K36me3 levels, respectively. Together, our results suggest that SDG102 is a methyltransferase that catalyzes the trimethylation of H3K36 of many genes across the maize genome, which are involved in multiple biological processes including those controlling flowering time.
A Novel Artificial Hemoglobin Carrier Based on Heulandite-Calcium Mesoporous Aluminosilicate Particles
Authors: Jordanoski Dino , Drobne Damjana , Repar Neža , Dogsa Iztok , Mrak Polona , Cerc-Korošec Romana , Škapin Andrijana Sever , Nadrah Peter , Poklar Ulrih Natasa
Published: July 2022

Tetraethyl-orthosilicate (TEOS)-based nanoparticles are most extensively used as a silica-based hemoglobin carrier system. However, TEOS-based nanoparticles induce adverse effects on the hemoglobin structure. Therefore, a heulandite-calcium-based carrier was investigated as a novel silica-based hemoglobin carrier system. The heulandite-calcium mesoporous aluminosilicate particles (MSPs) were fabricated by a patented tribo-mechanical activation process, according to the manufacturer, and its structure was assessed by X-ray diffraction analysis. Upon hemoglobin encapsulation, alternation in the secondary and tertiary structure was observed. The hemoglobin-particle interactions do not cause heme degradation or decreased activity. Once encapsulated inside the particle pores, the hemoglobin shows increased thermal stability, and higher loading capacity per gram of particles (by a factor of >1.4) when compared to TEOS-based nanoparticles. Futhermore, we introduced a PEGlyted lipid bilayer which significantly decreases the premature hemoglobin release and increases the colloidal stability. The newly developed hemoglobin carrier shows no cytotoxicity to human umbilical vein endothelial cells (HUVEC).
Bamboo Lignin Fractions with In Vitro Tyrosinase Inhibition Activity Downregulate Melanogenesis in B16F10 Cells via PKA/CREB Signaling Pathway
Authors: Choi Moon-Hee , Yang Seung-Hwa , Park Won-Keun , Shin Hyun-Jae
Published: July 2022

Cosmetic ingredients originating from natural resources have garnered considerable attention, and the demand for whitening ingredients is increasing, particularly in Asian countries. Lignin is a natural phenolic biopolymer significantly effective as a natural sunscreen, as its ultraviolet protection efficacy ranges from 250 to 400 nm. However, using different types of lignin as cosmetic ingredients is difficult owing to the heterogeneity of lignin and the lack of in vitro and in vivo safety and efficacy data. Thus, steam-exploded lignin (SEL) was prepared from bamboo, fractionated via successive organic solvent extraction, and sequentially fractionated using ethyl acetate, methanol, and acetone to investigate its potential as a natural whitening material. Gel permeation chromatography showed that the molecular weight of acetone-soluble and acetone-insoluble SEL fractions were the lowest and the highest, respectively. Monomer structures of the four lignin fractions were elucidated using 1H, 13C, and 2D heteronuclear single quantum coherence nuclear magnetic resonance and pyrolysis gas chromatography/mass spectrometry. The antioxidant and tyrosinase inhibition activities of the four fractions were compared. The methanol-soluble SEL fraction (SEL-F2) showed the highest antioxidant activity (except 2,2-diphenyl-1-picrylhydrazyl scavenging activity), and the enzyme inhibition kinetics were confirmed. In this study, the expression pattern of the anti-melanogenic-related proteins by SEL-F2 was confirmed for the first time via the protein kinase A (PKA)/cAMP-response element-binding (CREB) protein signaling pathway in B16F10 melanoma cells. Thus, SEL may serve as a valuable cosmetic whitening ingredient.
Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk
Authors: Gizzi Giulia , Cataldi Samuela , Mazzeschi Claudia , Delvecchio Elisa , Ceccarini Maria Rachele , Codini Michela , Albi Elisabetta
Published: July 2022

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa.
New Avenues of Heme Synthesis Regulation
Authors: Medlock Amy E. , Dailey Harry A.
Published: July 2022

During erythropoiesis, there is an enormous demand for the synthesis of the essential cofactor of hemoglobin, heme. Heme is synthesized de novo via an eight enzyme-catalyzed pathway within each developing erythroid cell. A large body of data exists to explain the transcriptional regulation of the heme biosynthesis enzymes, but until recently much less was known about alternate forms of regulation that would allow the massive production of heme without depleting cellular metabolites. Herein, we review new studies focused on the regulation of heme synthesis via carbon flux for porphyrin synthesis to post-translations modifications (PTMs) that regulate individual enzymes. These PTMs include cofactor regulation, phosphorylation, succinylation, and glutathionylation. Additionally discussed is the role of the immunometabolite itaconate and its connection to heme synthesis and the anemia of chronic disease. These recent studies provide new avenues to regulate heme synthesis for the treatment of diseases including anemias and porphyrias.
Next RNA Therapeutics: The Mine of Non-Coding
Authors: Garbo Sabrina , Maione Rossella , Tripodi Marco , Battistelli Cecilia
Published: July 2022

The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application.
Electrochemical Detection and Analysis of Various Current Responses of a Single Ag Nanoparticle Collision in an Alkaline Electrolyte Solution
Authors: Kim Ki Jun , Kwon Seong Jung
Published: July 2022

A single silver (Ag) nanoparticle (NP) collision was observed and analyzed in an alkaline solution using the electrocatalytic amplification (EA) method. Previously, the observation of a single Ag NP collision was only possible through limited methods based on a self-oxidation of Ag NPs or a blocking strategy. However, it is difficult to characterize the electrocatalytic activity of Ag NPs at a single NP level using a method based on the self-oxidation of Ag NPs. When using a blocking strategy, size analysis is difficult owing to the edge effect in the current signal. The fast oxidative dissolution of Ag NPs has been a problem for observing the staircase response of a single Ag NP collision signal using the EA method. In alkaline electrolyte conditions, Ag oxides are stable, and the oxidative dissolution of Ag NPs is sluggish. Therefore, in this study, the enhanced magnitude and frequency of the current response for single Ag NP collisions were obtained using the EA method in an alkaline electrolyte solution. The peak height and frequency of single Ag NP collisions were analyzed and compared with the theoretical estimation.
Molecular and Circulating Biomarkers in Patients with Glioblastoma
Authors: Senhaji Nadia , Squalli Houssaini Asmae , Lamrabet Salma , Louati Sara , Bennis Sanae
Published: July 2022

Glioblastoma is the most aggressive malignant tumor of the central nervous system with a low survival rate. The difficulty of obtaining this tumor material represents a major limitation, making the real-time monitoring of tumor progression difficult, especially in the events of recurrence or resistance to treatment. The identification of characteristic biomarkers is indispensable for an accurate diagnosis, the rigorous follow-up of patients, and the development of new personalized treatments. Liquid biopsy, as a minimally invasive procedure, holds promise in this regard. The purpose of this paper is to summarize the current literature regarding the identification of molecular and circulating glioblastoma biomarkers and the importance of their integration as a valuable tool to improve patient care.
Lactoferrin Deficiency Impairs Proliferation of Satellite Cells via Downregulating the ERK1/2 Signaling Pathway
Authors: Wang Xiong , Liu Fan , An Qin , Wang Wenli , Cheng Zhimei , Dai Yunping , Meng Qingyong , Zhang Yali
Published: July 2022

Lactoferrin (Ltf), a naturally active glycoprotein, possesses anti-inflammatory, anti-microbial, anti-tumor, and immunomodulatory activities. Many published studies have indicated that Ltf modulates the proliferation of stem cells. However, the role of Ltf in the proliferation of satellite cells, an important cell type in muscle regeneration, has not yet been reported. Here, by using Ltf systemic knockout mice, we illustrate the role of Ltf in skeletal muscle. Results shows that Ltf deficiency impaired proliferation of satellite cells (SCs) and the regenerative capability of skeletal muscle. Mechanistic studies showed that ERK1/2 phosphorylation was significantly downregulated after Ltf deletion in SCs. Simultaneously, the cell cycle-related proteins cyclin D and CDK4 were significantly downregulated. Intervention with exogenous recombinant lactoferrin (R-Ltf) at a concentration of 1000 μg/mL promoted proliferation of SCs. In addition, intraperitoneal injection of Ltf effectively ameliorated the skeletal muscle of mice injured by 1.2% BaCl2 solution. Our results suggest a protective effect of Ltf in the repair of skeletal muscle damage. Ltf holds promise as a novel therapeutic agent for skeletal muscle injuries.
Soybean Meal-Dependent Acute Intestinal Inflammation Delays Osteogenesis in Zebrafish Larvae
Authors: Carnovali Marta , Banfi Giuseppe , Porta Giovanni , Mariotti Massimo
Published: July 2022

Foods are known to be modulators of inflammation and skeletal development. The intestine plays an essential role in the regulation of bone health mainly through the regulation of the absorption of vitamin D and calcium; in fact, inflammatory bowel diseases are often related to bone health issues such as low bone mineral density, high fracture risk, osteoporosis and osteopenia. Considering the complexity of the pathways involved, the use of a simple animal model can be highly useful to better elucidate the pathogenic mechanisms. Soybean flour with a high saponin content has been used in many studies to induce intestinal inflammation in zebrafish larvae. Using a 50% soybean meal (SBM), we analyzed the effects of this soy-induced inflammatory bowel disease on zebrafish larval osteogenesis. Soybean meal induces intestinal functional alterations and an inflammatory state, highlighted by neutral red staining, without altering the general development of the larvae. Our data show that the chondrogenesis as well as endochondral ossification of the head of zebrafish larvae are not affected by an SBM-diet, whereas intramembranous ossification was delayed both in the head, where the length of the ethmoid plate reduced by 17%, and in the trunk with a delayed vertebral mineralization of 47% of SBM larvae. These data highlight that diet-dependent bowel inflammation can differently modulate the different mechanisms of bone development in different zones of the skeleton of zebrafish larvae.
Comparing Space Use and Fecal Glucocorticoid Concentrations during and after the COVID-19 Closure to Investigate Visitor Effects in Multiple Species
Authors: Edes Ashley N. , Liu Nathan C. , Baskir Eli , Bauman Karen L. , Kozlowski Corinne P. , Clawitter Helen L. , Powell David M.
Published: July 2022

We used the COVID-19 pandemic closure at the Saint Louis Zoo to examine visitor effects on space use and glucocorticoid levels in banteng, grizzly bears, polar bears, and western lowland gorillas. The study was divided into four six-week phases: closure in spring 2020, reopening in summer 2020, fall 2020, and spring 2021 as a seasonal comparison. Space use data were collected using video, and fecal samples were assayed for glucocorticoids. Generalized linear models were used to examine differences in zone occupancy and glucocorticoids between phases. The banteng spent more time near visitors, and glucocorticoids were only temporarily elevated in two of five animals when visitors returned. The grizzly bears spent more time in their habitat than in the den, and the polar bear spent more time near viewing areas after visitors returned. Glucocorticoids did not differ significantly between the closure and reopening for any bears. The gorillas spent less time close to visitors immediately after reopening but this effect waned by fall; glucocorticoid data were not available. Overall, based on space use and glucocorticoid levels, we suggest visitor effects on the gorillas are neutral, on the grizzly bears are neutral or positive, and are positive on the banteng and polar bear.
Realistic Gene Transfer to Gene Duplication Ratios Identify Different Roots in the Bacterial Phylogeny Using a Tree Reconciliation Method
Authors: Bremer Nico , Knopp Michael , Martin William F. , Tria Fernando D. K.
Published: July 2022

The rooting of phylogenetic trees permits important inferences about ancestral states and the polarity of evolutionary events. Recently, methods that reconcile discordance between gene-trees and species-trees—tree reconciliation methods—are becoming increasingly popular for rooting species trees. Rooting via reconciliation requires values for a particular parameter, the gene transfer to gene duplication ratio (T:D), which in current practice is estimated on the fly from discordances observed in the trees. To date, the accuracy of T:D estimates obtained by reconciliation analyses has not been compared to T:D estimates obtained by independent means, hence the effect of T:D upon inferences of species tree roots is altogether unexplored. Here we investigated the issue in detail by performing tree reconciliations of more than 10,000 gene trees under a variety of T:D ratios for two phylogenetic cases: a bacterial (prokaryotic) tree with 265 species and a fungal-metazoan (eukaryotic) tree with 31 species. We show that the T:D ratios automatically estimated by a current tree reconciliation method, ALE, generate virtually identical T:D ratios across bacterial genes and fungal-metazoan genes. The T:D ratios estimated by ALE differ 10- to 100-fold from robust, ALE-independent estimates from real data. More important is our finding that the root inferences using ALE in both datasets are strongly dependent upon T:D. Using more realistic T:D ratios, the number of roots inferred by ALE consistently increases and, in some cases, clearly incorrect roots are inferred. Furthermore, our analyses reveal that gene duplications have a far greater impact on ALE’s preferences for phylogenetic root placement than gene transfers or gene losses do. Overall, we show that obtaining reliable species tree roots with ALE is only possible when gene duplications are abundant in the data and the number of falsely inferred gene duplications is low. Finding a sufficient sample of true gene duplications for rooting species trees critically depends on the T:D ratios used in the analyses. T:D ratios, while being important parameters of genome evolution in their own right, affect the root inferences with tree reconciliations to an unanticipated degree.
6-Amino-3-(prop-2-en-1-yl)-9H-purin-3-ium Tetracopper(I) Hexabromide: Synthesis and X-ray Structure Determination
Authors: Pavlyuk Oleksiy V. , Slyvka Yurii I. , Goreshnik Evgeny A. , Mys’kiv Marian G.
Published: July 2022

6-Amino-3-(prop-2-en-1-yl)-9H-purin-3-ium tetracopper(I) hexabromide [(C5H5N5(C3H5))2Cu4Br6] (1) is synthesized in this paper. The title compound is characterized by Raman spectroscopy and single crystal X-ray diffraction: monoclinic, Sp.gr. P21/c, Z = 2, unit cell dimensions: a = 8.6870(3), b = 9.7447(2), c = 16.4418(4) Å, β = 100.681(3)°, V = 1367.72(7) Å3 at 150 K. The peculiarities of the metal coordination and distribution of weak interactions are analyzed. The significant role of hydrogen bonds in the construction of 1 crystal structure is shown.
Fatigue Life Prediction of CFRP-Strengthened RC Beams with Flexural Crack under Hygrothermal Environments
Authors: Guo Xinyan , Cui Hangyue , Wang Yilin , Chen Zhanbiao
Published: July 2022

The durability of reinforced concrete (RC) beams strengthened with carbon fiber-reinforced polymer (CFRP) is a worldwide concern in structural engineering. As an important part of the strengthened beam, the performance of the CFRP–concrete interface under hygrothermal environments is a delicate problem. In this paper, the fatigue behavior of CFRP-strengthened RC beams is analyzed by a theoretical model. In the model, CFRP–concrete interface degradation under hygrothermal environments is involved. Since interface debonding and rebar fracture induced by intermediate cracking are two typical failure modes, the damage models of rebar and the CFRP–concrete interface are established. Based on the theoretical model, the failure mode of CFRP-strengthened RC beams can be predicted, and fatigue life can be determined. The results showed that IC debonding is more likely to occur under hygrothermal environments. The accurate prediction of failure modes is essential for fatigue life prediction.
Study on Performance of Retarded Composite Semi-Rigid Base Mixed with Rubber Powder
Authors: Li Zhenxia , Guo Tengteng , Chen Yuanzhao , Wang Yunpeng , Chen Yanyan , He Qingyun , Yang Xiao , Wang Jing
Published: July 2022

In order to solve the problem of poor crack resistance and frost resistance of semi-rigid base, rubber powder and retarder were added to a semi-rigid base mixture. First, 61 mixing ratios were determined. Then, through the unconfined compressive strength, splitting strength, and other tests, the mechanical, crack, and frost resistance properties of the retarded composite semi-rigid base coarse mixture with rubber powder were studied. Finally, the macro and micro properties of the two kinds of admixture composite semi-rigid base coarse mixtures were studied by means of SEM and industrial CT. The results show that rubber powder and retarder can effectively improve the cracking and freezing resistance of the mixture. After five freeze–thaw cycle tests, the strength of the retarded composite semi-rigid base material mixed with rubber powder decreased slightly compared with the mixture without additives. It can be seen that rubber powder improved the frost resistance of the mixture. When the content of rubber powder was 1.5%, the BDR value of the mixture increased by 8.8%. With the increase of unconfined compressive strength, splitting strength, and flexural tensile strength at 28 d and 90 d, it was found that the retarder improved the middle and late strength of the mixture. When the content of retarder was 0.09%, the increase of unconfined compressive strength at 28 d reached 3.9%. The addition of rubber powder and retarder improved the distribution of internal pores, the proportion of large pores decreased, and the proportion of small pores increased. The retarder changed the morphology of hydration products, formed a dense network supporting structure, further refined the pores, and reduced the porosity of the mixture. The proportion of pores with a volume greater than 100 mm3 in the total pore volume decreased by 26.01%, and the proportion of medium pores increased by 13.07%, thereby improving the mechanical properties of the mixture.
The Influence of Tool Pin Geometry and Speed on the Mechanical Properties of the Bobbin Tool Friction Stir Processed AA1050
Authors: Ahmed Mohamed M. Z. , El-Sayed Seleman Mohamed M. , Eid Rana G. , Albaijan Ibrahim , Touileb Kamel
Published: July 2022

AA1050 plates of 8 mm thickness were processed via bobbin-tool friction stir processing technique at a constant rotation speed of 600 rpm and different travel speeds ranging from 50 to 300 mm/min using three-pin geometries of triangle, square, and cylindrical. The temperatures of the processed zone, the advancing side, and the retreating side were measured; the machine torque during processing was also recorded. The processed materials were evaluated in terms of surface roughness, macrostructure, tensile properties, and hardness measurements. The fracture surfaces of the tensile fractured specimens were investigated using SEM. The results indicated that the pin geometry and processing speed significantly affect the generated heat input and the morphology of the processed zone. The peak temperature in the center of the processed zone decreases with increasing the travel speed from 50 to 300 mm/min at all applied pin geometries. The maximum temperature of ~400 °C was reached using the cylindrical pin geometry. The machine torque increases with increasing the travel speed at all applied pin geometries, and the highest torque value of 73 N.m is recorded using the square pin geometry at 300 mm/min travel speed. The top surface roughness of the processed area using the cylindrical pin is lower than that given by the other pin geometries. Under all applied conditions, the hardness of the processed area increases with increasing travel speed, and the cylindrical pin shows a higher hardness than the other pin geometries with 19% enhancement over the BM. The AA1050 processed using a cylindrical pin at 200 mm/min travel speed and a rotation speed of 600 rpm produces a sound processing zone with the highest ultimate tensile strength of 79 MPa.
Repair of Bulk-Fill and Nanohybrid Resin Composites: Effect of Surface Conditioning, Adhesive Promoters, and Long-Term Aging
Authors: Ugurlu Muhittin , Al-Haj Husain Nadin , Özcan Mutlu
Published: July 2022

The aim of the study was to investigate the effect of different repair procedures on the repair bond strength of bulk-fill and nanohybrid resin composites after different aging periods. The resin composite blocks (8 × 8 × 4 mm3) were prepared from a bulk-fill (reliaFIL Bulk) and a nanohybrid (reliaFIL LC) resin composite and grouped according to aging duration (6 months, 1 year, and 2 years). Following aging, the blocks were assigned to different surface treatments; air-abrasion with aluminum oxide powder, roughening with a diamond bur, and no treatment. After cleansing with phosphoric acid, a silane layer (Porcelain Primer) was applied on the surface of half of the specimens in each group. The specimens were subdivided into two groups (n = 5): Scotchbond Universal (3M Oral Care) and All-Bond Universal (Bisco). The blocks were repaired with the nanohybrid composite (8 × 8 × 8 mm 3). The repaired specimens were stored in distilled water (37 °C/24 h) and segmented into beams. Half of the beams were immediately subjected to microtensile μTBS testing (1 mm/min), while the other half was stored in distilled water (37 °C) for 6 months before testing. Failure modes were analyzed using stereomicroscope and SEM. Statistical analyses were performed with ANOVA and least significant difference tests (LSD) tests (p = 0.05). The extension of aging periods (6 months, 1 year, and 2 years) reduced the repair bond strength in some groups for both resin composites (p < 0.05). The air-abrasion and bur roughening improved the repair bond strength (p < 0.05). The silane application did not influence the repair bond strength and durability (p > 0.05). There was no difference among the universal adhesives in the same surface treatment groups (p > 0.05). The mechanical roughening treatments are necessary for the repair of resin composite. The universal adhesives might be used for the repair of resin composites regardless of silane content without prior silane application.