bluuebunny/crossref_metadata_2025 huggingface dataset:
Ending the Social Normalization of Violence against Children in Canada: A Framework, Rationale, and Appeal to Canadian Faith Leaders
Authors: Michaelson Valerie , Ensom Ron
Published: December 2022

Corporal punishment remains the most common form of violence against children in Canada. Along with being legally permitted, it is made socially acceptable through cultural and social norms often disguised as discipline. Paraphrases of Judeo-Christian sacred texts such as “spare the rod; spoil the child” have been widely used to justify corporal punishment, and to create norms around the idea that it is a god-given responsibility of parents to inflict corporal punishment on their children “for their own good.” Corporal punishment is then not only an acceptable part of raising children but can be a godly duty. Though Canada is a secular country, this social norm provides a moral hegemony under which violence becomes the status quo and has proven very difficult to change. In this commentary, we outline the ways that Christian religion has contributed to social norms around corporal punishment. We then argue that religious leaders have an opportunity—and moral responsibility—to contribute to change. We conclude with insights from social norms theory and offer evidence-based recommendations for ways forward that could help shift attitudes around corporal punishment in order to decrease its prevalence and harm. While each of these issues has been written about extensively in isolation, this commentary offers an analysis of these matters together under one umbrella. By making this relationship between Christianity and the social norms that propagate corporal punishment more visible, we draw attention to the role leaders in Christian churches could play in disrupting the social acceptance of violence against our youngest Canadian citizens. We provide a practical and evidence-based framework, rationale, and appeal to Canadian faith leaders to use their influence to add momentum to a critical health, rights—and religion—issue in Canada.
The Over-the-Counter Medicines Market in Poland
Authors: Lasota Dorota , Mirowska-Guzel Dagmara , Goniewicz Mariusz
Published: December 2022

The market of over-the-counter drugs, so-called OTC drugs, is a dynamically developing market driven primarily by self-medication. Their use does not require consultation with a physician, and the patients themselves decide to take them. The distribution of OTC medications in the pharmaceutical market in Poland is diversified. These drugs could be purchased at a pharmacy but also at a supermarket, gas station, or via the internet. The low involvement of public funds in spending on drugs, a relatively small percentage of pharmacy sales of reimbursable prescription drugs, and the difficult access to physicians or general consent to drug advertising all create ideal conditions for creating demand for these drugs. Among the European countries, Poland also has the largest share of OTC drugs in the entire pharmaceutical market, and the percentage of OTCs (without supplements) in the whole drug market in Poland continues to grow. Unfortunately, the non-pharmacy market for the sale of OTC drugs is not adequately controlled in practice, and Polish legal regulations regarding the sale of medicines outside pharmacies are among the most liberal in the European Union. However, this does not change the general attitude of consumers toward purchasing OTC drugs. In fact, further growth of the OTC drug market is forecast. Self-medication will undoubtedly play an important role in the trends which may shape this market in the coming years.
Factors Influencing the Executive Functions of Male and Female Cadets
Authors: Zurek Grzegorz , Lenart Dariusz , Lachowicz Maciej , Zebrowski Krzysztof , Jamro Dariusz
Published: December 2022

Executive functions (EFs) are related to human abilities that allow individuals to achieve planned goals, contribute to creativity and the analysis of new ideas, and allow for adaptation to new situations in daily life. Thorough analyses of the factors affecting EFs can aid in the development of appropriate training programs for various social and professional groups, including the military. The purpose of this study was to determine the factors affecting the EFs of cadets (18 women and 108 men) studying at a military academy in Poland after the first and second terms of military training, and to investigate gender differences in the level of EFs, shooting performance (SP), and components of physical fitness (PF). The Neuropsychological Color Trails Test (CTT-2) was used to determine some of the EFs of the test subjects. Meanwhile, the level of SP was represented by the score achieved during marksmanship training implemented during military training. Assessment of the subjects’ PF was guided by the principles of the Health-Related Fitness assessment concept, i.e., health-related fitness. Differences between men and women in specific variables were calculated using the Mann–Whitney U test for independent samples, whilst the relationship between variables was analyzed using the best subset regression method. The results revealed that cadets’ EFs were influenced by their SP and their level of strength. However, there were no significant differences between male and female cadets in the levels of EFs or SP.
Alcohol Policies Affect Drinking Patterns—A Potentially New and Harmful Drinking Pattern in Consumers of Small Vodka Bottles (SVB) in Poland
Authors: Silczuk Andrzej , Mańczak Małgorzata , Owoc Jakub
Published: December 2022

Drinking alcohol has a vast and diverse impact on many aspects of people’s lives around the world. It is a major public health concern and is subject to numerous legal regulations and limitations. So far, little attention has been paid to if and how the volume of alcohol containers may affect drinking patterns. The widespread availability in recent years in Poland of small vodka bottles in various flavors and sizes was the rationale behind investigating whether the phenomenon may affect drinking patterns in any way. This was a 12-month cross-sectional survey study that started in January 2020. It included a total of 217 inpatients and outpatients that met the ICD-10 alcohol dependence criteria. The respondents were asked about their drinking habits and the use of small vodka bottles. It was found that respondents who regularly use small vodka bottles were much more likely to start their drinking early in the morning. The widespread availability and selection of small vodka bottles may encourage and facilitate drinking that starts early in the morning. It also makes it easier to maintain and control intoxication throughout the whole day, which could be considered another drinking pattern different from the other well-established ones, such as binge or continuous drinking. However, the design of this study makes it impossible to draw firm conclusions and further research is necessary.
No Mitochondrial Related Transcriptional Changes in Human Skeletal Muscle after Local Heat Application
Authors: Kwon Monica , Robins Larry , McGlynn Mark L. , Collins Christopher , Pekas Elizabeth J. , Park Song-Young , Slivka Dustin
Published: December 2022

The purpose of the study is to determine the impact of local heating on skeletal muscle transcriptional response related to mitochondrial biogenesis and mitophagy. Twelve healthy subjects (height, 176.0 ± 11.9 cm; weight, 83.6 ± 18.3 kg; and body composition, 19.0 ± 7.7% body fat) rested in a semi-reclined position for 4 h with a heated thermal wrap (HOT) around one thigh and a wrap without temperature regulation (CON) around the other (randomized). Skin temperature, blood flow, intramuscular temperature, and a skeletal muscle biopsy from the vastus lateralis were obtained after the 4 h intervention. Skin temperature via infrared thermometer and thermal camera was higher after HOT (37.3 ± 0.7 and 36.7 ± 1.0 °C, respectively) than CON (34.8 ± 0.7, 35.2 ± 0.8 °C, respectively, p < 0.001). Intramuscular temperature was higher in HOT (36.3 ± 0.4 °C) than CON (35.2 ± 0.8 °C, p < 0.001). Femoral artery blood flow was higher in HOT (304.5 ± 12.5 mL‧min−1) than CON (272.3 ± 14.3 mL‧min−1, p = 0.003). Mean femoral shear rate was higher in HOT (455.8 ± 25.1 s−1) than CON (405.2 ± 15.8 s−1, p = 0.019). However, there were no differences in any of the investigated genes related to mitochondrial biogenesis (PGC-1α, NRF1, GAPBA, ERRα, TFAM, VEGF) or mitophagy (PINK-1, PARK-2, BNIP-3, BNIP-3L) in response to heat (p > 0.05). These data indicate that heat application alone does not impact the transcriptional response related to mitochondrial homeostasis, suggesting that other factors, in combination with skeletal muscle temperature, are involved with previous observations of altered exercise induced gene expression with heat.
The Importance of Place Attachment in the Understanding of Ageing in Place: “The Stones Know Me”
Authors: Lebrusán Irene , Gómez M. Victoria
Published: December 2022

As academic literature has shown, there is a preference among older adults to experience old age independently, in their own homes, giving shape to what has been called ageing in place. This phenomenon links residence, life cycle, and the experience of old age. Although it depends on many factors (housing characteristics, the elderly’s economy, or their social support, among others) it is based on place attachment as a key aspect, which comprises two different but interwoven dimensions: the home (private space) and the neighbourhood (social space), understood as an extended sphere of the home. Despite its importance, and beyond the consensus that the time spent in a place increases attachment to it, the processes whereby place attachment is constructed by the elderly and the role of the experience of neighbourhood are little known. This article intended to delve into the meaning of place attachment, its importance, and how it is built by the elderly population in urban areas. For this purpose, a qualitative study was conducted in Spain, selecting Madrid (the biggest city in the country) as a case study of how place attachment is shaped in an urban setting. To obtain in-depth information, data were collected through ethnographic interviews with 37 people aged 65–95 and 1 focus group among elderly aged 65–71. The most relevant finding of the qualitative analysis is the emotional significance of attachment to the local space as an element that enables continuity—as opposed to the rupture to which we associate old age- in the experience of the life cycle of the elderly. It should be noted that some of the results are conditioned by the specificities of Spanish society, particularly with regard to family ties. Potential extrapolations to other realities should take this point into account.
Research on Voluntary Carbon Information Disclosure Mechanism of Enterprises from the Perspective of Stakeholders—A Case Study on the Automobile Manufacturing Industry
Authors: Guo Chensi , Pan Wenyan
Published: December 2022

As the primary source of carbon emissions, enterprises must work hard to save energy, reduce emissions, and disclose timely carbon information to the public. As a key means of communicating carbon management performance to stakeholders, carbon information disclosure is directly tied to the future sustainability of enterprises. Based on panel data of 118 listed firms in the automotive manufacturing industry from 2017 to 2021, this study rates the sample companies’ quality of carbon information disclosure. The impact of the government, creditors, media, employees, and suppliers on such disclosure is also examined from the stakeholders’ standpoint. The findings reveal that: (1) Although there has been a gradual increase in the degree of disclosure, overall levels are still low, and the willingness to voluntarily disclose is insufficient. (2) When other variables are neglected, the government, creditors, media, and employees all assist enterprises in disclosing carbon information, but the influence of suppliers will inhibit such disclosure. In the context of a complex economic system, the level of carbon disclosure is positively correlated with the government, the media, and employees, while negatively correlated with creditors. The influence of suppliers is not significant. These findings may aid in formulating related policies from different dimensions, directing enterprises to publish carbon information actively and strengthening carbon management.
Preventive Health Behaviours among Adolescents and Their Parents during the COVID-19 Outbreak in the Light of the Health Beliefs Model
Authors: Koźlarek Marietta , Błaszczyk Natalia , Grajek Magdalena , Jaskulska Sylwia
Published: December 2022

This article analysed the relationship between the preventive health behaviours of parents and teenagers during the COVID-19 outbreak, taking the Health Beliefs Model (HBM) as a point of reference. We assumed that parents’ behaviours may be a cue to action for adolescents, looking at their preventive health behaviours regarding vaccination against COVID-19, as well as vaccination intention (among unvaccinated people); wearing protective masks where it is compulsory and where it is not obligatory; and maintaining physical distance and disinfecting hands in public places. The collected data were statistically analysed using the Statistica version 13.3 software package for advanced statistical data analysis. Descriptive statistics and correlation for non-parametric data (Spearman’s correlation) were used. Research on a sample of 201 parents and their children revealed that young people engage in preventive behaviour less frequently than parents, but that the likelihood of such behaviour increases if they have a parent’s cue to action. When formulating recommendations, we considered the gender of the surveyed parents, as the questionnaire was mainly completed by women, which may be an indicator of the unequal involvement in addressing the topic of the pandemic and preventive health behaviours, including attitudes towards vaccines.
Oral Health Barriers for African American Caregivers of Autistic Children
Authors: Como Dominique H. , Floríndez-Cox Lucía I. , Stein Duker Leah I. , Cermak Sharon A.
Published: December 2022

The most persistent oral health disparities in the United States impact children from racial and ethnic minoritized groups and children diagnosed as autistic. This paper aims to describe barriers to oral care as depicted by Black/African American (B/AA) parents of autistic children to further explore how and why oral health disparities persist in this population. A purposeful sample of eleven caregivers of autistic children, ages 4 to 14 years, who identified as B/AA were interviewed twice for approximately 60–90 min each. Thematic analysis utilizing a narrative approach was employed. Three themes emerged from the data concerning the barriers that affect oral health experiences: (a) difficulty in maintaining good oral health practices, (b) challenges with access to care and resources, and (c) poor patient-provider relationships. Due to the limited research that examines the intersection of autism, B/AA culture, and oral health practices, this study provides a rich picture of the barriers families face when obtaining oral care. Many families raised issues that other parents of autistic children also identified. B/AA caregivers have demonstrated that despite their own negative dental experiences, they understand the value of good oral care practices and are willing to pursue oral care for their children.
Job Satisfaction Goes a Long Way: The Mediating Role of Teaching Satisfaction in the Relationship between Role Stress and Indices of Psychological Well-Being in the Time of COVID-19
Authors: Padmanabhanunni Anita , Pretorius Tyrone Brian
Published: December 2022

The COVID-19 pandemic and its containment measures has resulted in drastic changes in the educational landscape. Teachers had to rapidly adapt to shifts in their work-related roles and responsibilities. This situation likely led to role stress and affected the levels of job satisfaction, mental health and general life satisfaction. In this study, we examined the role of teachers’ job satisfaction in the relationship between role stress and indices of psychological well-being. The participants were South African school teachers (N = 355) who completed the Role Orientation Questionnaire, the Teaching Satisfaction Scale, the Center for Epidemiological Studies Depression Scale, the trait scale of the State-Trait Anxiety Inventory and the Satisfaction with Life Scale. In addition to descriptive statistics and correlations, path analysis was performed to determine the mediating role of teaching satisfaction. Increased levels of teaching satisfaction were associated with decreased levels of depression and anxiety and increased levels of life satisfaction. Teaching satisfaction also mediated the relationship between role conflict, as well as role ambiguity and anxiety. The results indicated that teaching satisfaction is a critical protective factor for teachers. Thus, improving task significance and enhancing the meaning associated with the teaching profession may help promote the adaptive functioning of teachers.
Exploring the Role of Land Transfer and Social Capital in Improving Agricultural Income under the Background of Rural Revitalization
Authors: Yu Haiyan , Zhang Wenjie , Pang Shuai
Published: December 2022

Under the background of rural revitalization in China, with the process of urbanization and the implementation of China’s land system reform, rural workers gradually gain multiple income streams. However, increasing agricultural income remains the final guarantee for professional farmers to shake off poverty, and land is still their last security. We applied the OLS model and mediation model to a dataset of 3789 households in 25 provinces obtained from China Family Panel Studies (CFPS) to investigate the influence of farmland transfer and social capital on farmers’ agricultural incomes. The results show that farmland “transfer in” and social capital significantly help to increase agricultural income directly, and farmland “transfer in” behavior plays a vital mediating role, influencing the positive effect of social capital on agricultural income. The study examined the logical social capital-agricultural land transfer-agricultural income correlation in the progression of rural society, from “hollow” to “reflux”, under the continuous expansion of rural revitalization strategies, which is of great practical significance for re-recognizing the positive role of rural social capital and agricultural land transfer in improving the income of professional farmers and realizing the overall goal of rural revitalization. The results also provide a theoretical basis for guiding and leveraging the effective use of social capital to promote agricultural land transfer.
Examining the Association between Sports Participation and Mental Health of Adolescents
Authors: Khan Asaduzzaman , Ahmed Kazi R. , Hidajat Tarissa , Edwards Elizabeth J.
Published: December 2022

Sports participation has been linked to various health outcomes; however, there is scant literature exploring this relationship in developing countries. We used a mixed method approach to examine the association between sports participation and mental health of Bangladeshi adolescents (n = 320; 13–17 years; 59% boys) and to explore sports preferences and barriers to sports participation across genders. A survey collected team and non-team sports participation, depression, and life satisfaction. Focus groups (16 boys, 16 girls) explored preferences for, and barriers to, sports participation. Regression analysis showed that higher team and non-team sports participation were associated with lower depressive symptoms in boys (β = −1.22, 95% CI:−2.55 to −0.10; β = −2.50, 95% CI:−3.83 to −1.16, respectively), while greater participation in team sports was associated with less depression in girls (β = −2.44, 95% CI:−4.63 to −0.24). Participation in team and non-team sports was positively associated with life satisfaction for boys and girls. Boys reported preferences for playing football and cricket, while girls favored skipping and running. Prolonged time on electronic devices was reported as barriers to sports participation in both genders. Furthermore, household chores, family restrictions, and unsafe environment were reported by girls. Participation in team sports may provide mental health benefits for both genders, while non-team sports may be more beneficial to boys than girls.
Climate Change and Nutrition: Implications for the Eastern Mediterranean Region
Authors: Al-Jawaldeh Ayoub , Nabhani Maya , Taktouk Mandy , Nasreddine Lara
Published: December 2022

The Eastern Mediterranean Region (EMR) is considered among the world’s most vulnerable to the dire impacts of climate change. This review paper aims at (1) characterizing climate change in countries of the EMR; (2) examining the potential effects of climate change on the nutritional and health status of the population; and (3) identifying the most vulnerable population groups. The paper explored several climate change indicators including daily temperatures, extreme temperature, daily precipitation, extreme precipitation (flooding, drought, storms, etc.), humidity, CO2 concentrations and sea surface temperature in EMR countries. Findings suggest that climate change will exert a significant adverse effect on water and food security and showed that the nutritional status of the population, which is already characterized by the triple burden of malnutrition, is likely to worsen via three main pathways mediated by climate change, namely, its impact on food security, care and health. Women, infants, children, those living in poor households and those experiencing displacement will be among the most vulnerable to the nutritional impacts of climate change. The paper concludes with a set of recommendations from the Initiative on Climate Action and Nutrition, which can support the region in tackling the critical nexus of climate change and nutrition.
Influence of Metal Salts Addition on Physical and Electrochemical Properties of Ethyl and Propylammonium Nitrate
Authors: Ausín David , Trenzado José L. , Turmine Mireille , Varela Luis M. , Cabeza Oscar , González Romero Elisa , Segade Luisa
Published: December 2022

In this work, we deepen in the characterization of two protic ionic liquids (PILs), ethylammonium nitrate (EAN) and propylammonium nitrate (PAN). With this aim, we determined the influence of inorganic nitrate salts addition on their physical properties and their electrochemical potential window (EPW). Thus, experimental measurements of electrical conductivity, density, viscosity, refractive index and surface tension of mixtures of {EAN or PAN + LiNO3, Ca(NO3)2, Mg(NO3)2 or Al(NO3)3} at a temperature range between 5 and 95 °C are presented first, except for the last two properties which were measured at 25 °C. In the second part, the corresponding EPWs were determined at 25 °C by linear sweep voltammetry using three different electrochemical cells. Effect of the salt addition was associated mainly with the metal cation characteristics, so, generally, LiNO3 showed the lower influence, followed by Ca(NO3)2, Mg(NO3)2 or Al(NO3)3. The results obtained for the EAN + LiNO3 mixtures, along with those from a previous work, allowed us to develop novel predictive equations for most of the presented physical properties as functions of the lithium salt concentration, the temperature and the water content. Electrochemical results showed that a general order of EPW can be established for both PILs, although exceptions related to measurement conditions and the properties of the mixtures were found.
Ivermectin Attenuates CCl4-Induced Liver Fibrosis in Mice by Suppressing Hepatic Stellate Cell Activation
Authors: Ying Hanglu , Li Long , Zhao Yufen , Ni Feng
Published: December 2022

Liver fibrosis, a common liver dysfunction with high morbidity and mortality rates, is the leading cause of cirrhosis and hepatocellular carcinoma, for which there are no effective therapies. Ivermectin is an antiparasitic drug that also has been showing therapeutic actions in many other diseases, including antiviral and anticancer actions, as well as treating metabolic diseases. Herein, we evaluated the function of ivermectin in regulating liver fibrosis. Firstly, carbon tetrachloride (CCl4)-injected Balb/c mice were used to assess the antifibrosis effects of ivermectin in vivo. Further, CFSC, a rat hepatic stellate cell (HSC) line, was used to explore the function of ivermectin in HSC activation in vitro. The in vivo data showed that ivermectin administration alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, the ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, the ivermectin administration significantly decreased the protein levels of α-smooth muscle actin (α-SMA) both in vivo and in vitro, suggesting that the antifibrotic effects of ivermectin are mainly due to the promotion of HSC deactivation. The present study demonstrates that ivermectin may be a potential therapeutic agent for the prevention of hepatic fibrosis.
Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation
Authors: Hashimoto Yu , Yamasaki Ryo , Ko Senri , Matsuo Eriko , Kobayakawa Yuko , Masaki Katsuhisa , Matsuse Dai , Isobe Noriko
Published: December 2022

Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice. Cx30 was highly expressed in the pre-onset stage in mSOD1 mice. mSOD1 mice with knockout (KO) of the Cx30 gene (Cx30KO-mSOD1 mice) showed delayed disease onset and tended to have an extended survival period (log-rank, p = 0.09). At the progressive and end stages of the disease, anterior horn cells were significantly preserved in Cx30KO-mSOD1 mice. In lesions of these mice, glial fibrillary acidic protein/C3-positive inflammatory astroglia were decreased. Additionally, the activation of astrocytes in Cx30KO-mSOD1 mice was reduced compared with mSOD1 mice by gene expression microarray. Furthermore, expression of connexin 43 at the pre-onset stage was downregulated in Cx30KO-mSOD1 mice. These findings suggest that reduced expression of astroglial Cx30 at the early disease stage in ALS model mice protects neurons by attenuating astroglial inflammation.
Genome-Wide Analysis and Characterization of Eggplant F-Box Gene Superfamily: Gene Evolution and Expression Analysis under Stress
Authors: Wang Yixi , Li Chuhao , Yan Shuangshuang , Yu Bingwei , Gan Yuwei , Liu Renjian , Qiu Zhengkun , Cao Bihao
Published: December 2022

F-box genes play an important role in plant growth and resistance to abiotic and biotic stresses. To date, systematic analysis of F-box genes and functional annotation in eggplant (Solanum melongena) is still limited. Here, we identified 389 F-box candidate genes in eggplant. The domain study of F-box candidate genes showed that the F-box domain is conserved, whereas the C-terminal domain is diverse. There are 376 SmFBX candidate genes distributed on 12 chromosomes. A collinearity analysis within the eggplant genome suggested that tandem duplication is the dominant form of F-box gene replication in eggplant. The collinearity analysis between eggplant and the three other species (Arabidopsis thaliana, rice and tomato) provides insight into the evolutionary characteristics of F-box candidate genes. In addition, we analyzed the expression of SmFBX candidate genes in different tissues under high temperature and bacterial wilt stress. The results identified several F-box candidate genes that potentially participate in eggplant heat tolerance and bacterial wilt resistance. Moreover, the yeast two-hybrid assay showed that several representative F-box candidate proteins interacted with representative Skp1 proteins. Overexpression of SmFBX131 and SmFBX230 in tobacco increased resistance to bacterial wilt. Overall, these results provide critical insights into the functional analysis of the F-box gene superfamily in eggplant and provide potentially valuable targets for heat and bacterial resistance.
Long Noncoding RNAs in the Pathogenesis of Insulin Resistance
Authors: Yang Weili , Lyu Yixiang , Xiang Rui , Yang Jichun
Published: December 2022

Insulin resistance (IR), designated as the blunted response of insulin target tissues to physiological level of insulin, plays crucial roles in the development and progression of diabetes, nonalcoholic fatty liver disease (NAFLD) and other diseases. So far, the distinct mechanism(s) of IR still needs further exploration. Long non-coding RNA (lncRNA) is a class of non-protein coding RNA molecules with a length greater than 200 nucleotides. LncRNAs are widely involved in many biological processes including cell differentiation, proliferation, apoptosis and metabolism. More recently, there has been increasing evidence that lncRNAs participated in the pathogenesis of IR, and the dysregulated lncRNA profile played important roles in the pathogenesis of metabolic diseases including obesity, diabetes and NAFLD. For example, the lncRNAs MEG3, H19, MALAT1, GAS5, lncSHGL and several other lncRNAs have been shown to regulate insulin signaling and glucose/lipid metabolism in various tissues. In this review, we briefly introduced the general features of lncRNA and the methods for lncRNA research, and then summarized and discussed the recent advances on the roles and mechanisms of lncRNAs in IR, particularly focused on liver, skeletal muscle and adipose tissues.
Extracellular Events Involved in Cancer Cell–Cell Fusion
Authors: Dittmar Thomas , Hass Ralf
Published: December 2022

Fusion among different cell populations represents a rare process that is mediated by both intrinsic and extracellular events. Cellular hybrid formation is relayed by orchestrating tightly regulated signaling pathways that can involve both normal and neoplastic cells. Certain important cell merger processes are often required during distinct organismal and tissue development, including placenta and skeletal muscle. In a neoplastic environment, however, cancer cell fusion can generate new cancer hybrid cells. Following survival during a subsequent post-hybrid selection process (PHSP), the new cancer hybrid cells express different tumorigenic properties. These can include elevated proliferative capacity, increased metastatic potential, resistance to certain therapeutic compounds, and formation of cancer stem-like cells, all of which characterize significantly enhanced tumor plasticity. However, many parts within this multi-step cascade are still poorly understood. Aside from intrinsic factors, cell fusion is particularly affected by extracellular conditions, including an inflammatory microenvironment, viruses, pH and ionic stress, hypoxia, and exosome signaling. Accordingly, the present review article will primarily highlight the influence of extracellular events that contribute to cell fusion in normal and tumorigenic tissues.
MbICE1 Confers Drought and Cold Tolerance through Up-Regulating Antioxidant Capacity and Stress-Resistant Genes in Arabidopsis thaliana
Authors: Duan Yadong , Han Jiaxin , Guo Baitao , Zhao Wenbo , Zhou Shuang , Zhou Chunwei , Zhang Lei , Li Xingguo , Han Deguo
Published: December 2022

Malus baccata (L.) Borkh is an apple rootstock with good drought and cold resistance. The ICE gene is a key factor in the molecular mechanisms of plant drought and cold resistance. In the present research, the function of drought- and cold-induced MbICE1 of Malus baccata was investigated in Arabidopsis. According to GFP fluorescence images, MbICE1 was determined to be a nuclear protein. The MbICE1 was transferred to Arabidopsis, showing enhanced tolerance to drought and cold stresses. Under drought and cold treatments, the transgenic Arabidopsis had higher chlorophyll content and free proline content than WT plants, but the Malondialdehyde (MDA) content and electrolyte leakage (EL) were lower than those of WT plants. In addition, drought and cold led to a large accumulation of ROS (H2O2 and O2−) content in Arabidopsis, while overexpression of MbICE1 enhanced the antioxidant enzyme activity in Arabidopsis and improved the plant’s resistance to stresses. Moreover, the accumulation of MbICE1 promoted the expression of AtCBF1, AtCBF2, AtCBF3, AtCOR15a, AtCOR47 and AtKIN1 genes in Arabidopsis. These data indicate that MbICE1 is a key regulator of drought and cold and can be used as a backup gene for breeding Malus rootstocks.
New Insights into MdSPS4-Mediated Sucrose Accumulation under Different Nitrogen Levels Revealed by Physiological and Transcriptomic Analysis
Authors: Cao Xuejing , Li Wenfang , Wang Ping , Ma Zonghuan , Mao Juan , Chen Baihong
Published: December 2022

Nitrogen nutrition participates in many physiological processes and understanding the physiological and molecular mechanisms of apple responses to nitrogen is very significant for improving apple quality. This study excavated crucial genes that regulates sugar metabolism in response to nitrogen in apples through physiology and transcriptome analysis, so as to lay a theoretical foundation for improving fruit quality. In this paper, the content of sugar and organic acid in apple fruit at different developmental periods under different nitrogen levels (0, 150, 300, and 600 kg·hm−2) were determined. Then, the transcriptomic analysis was performed in 120 days after bloom (DAB) and 150 DAB. The results showed that the fructose and glucose content were the highest at 120 DAB under 600 kg·hm−2 nitrogen level. Meanwhile, different nitrogen treatments decreased malate content in 30 and 60 DAB. RNA-seq analysis revealed a total of 4537 UniGenes were identified as differentially expressed genes (DEGs) under nitrogen treatments. Among these DEGs, 2362 (52.06%) were up-regulated and 2175 (47.94%) were down-regulated. The gene co-expression clusters revealed that most DEGs were significantly annotated in the photosynthesis, glycolysis/gluconeogenesis, pyruvate metabolism, carbon metabolism, carbon fixation in photosynthetic organisms and plant hormone signal transduction pathways. The key transcription factor genes (ERF, NAC, WRKY, and C2H2 genes) were differentially expressed in apple fruit. Sugar and acid metabolism-related genes (e.g., HXK1, SPS4, SS2, PPC16-2, and MDH2 genes) exhibited significantly up-regulated expression at 120 DAB, whereas they were down-regulated at 150 DAB. Furthermore, the MdSPS4 gene overexpression positively promoted sucrose accumulation in apple callus and fruit. In conclusion, the combinational analysis of transcriptome and the functional validation of the MdSPS4 gene provides new insights into apple responses to different nitrogen levels.
Comparison of Bioluminescent Substrates in Natural Infection Models of Neglected Parasitic Diseases
Authors: Hendrickx Sarah , Bulté Dimitri , Mabille Dorien , Mols Roxanne , Claes Mathieu , Ilbeigi Kayhan , Ahmad Rokaya , Dirkx Laura , Van Acker Sara I. , Caljon Guy
Published: December 2022

The application of in vivo bioluminescent imaging in infectious disease research has significantly increased over the past years. The detection of transgenic parasites expressing wildtype firefly luciferase is however hampered by a relatively low and heterogeneous tissue penetrating capacity of emitted light. Solutions are sought by using codon-optimized red-shifted luciferases that yield higher expression levels and produce relatively more red or near-infrared light, or by using modified bioluminescent substrates with enhanced cell permeability and improved luminogenic or pharmacokinetic properties. In this study, the in vitro and in vivo efficacy of two modified bioluminescent substrates, CycLuc1 and AkaLumine-HCl, were compared with that of D-luciferin as a gold standard. Comparisons were made in experimental and insect-transmitted animal models of leishmaniasis (caused by intracellular Leishmania species) and African trypanosomiasis (caused by extracellular Trypanosoma species), using parasite strains expressing the red-shifted firefly luciferase PpyRE9. Although the luminogenic properties of AkaLumine-HCl and D-luciferin for in vitro parasite detection were comparable at equal substrate concentrations, AkaLumine-HCl proved to be unsuitable for in vivo infection follow-up due to high background signals in the liver. CycLuc1 presented a higher in vitro luminescence compared to the other substrates and proved to be highly efficacious in vivo, even at a 20-fold lower dose than D-luciferin. This efficacy was consistent across infections with the herein included intracellular and extracellular parasitic organisms. It can be concluded that CycLuc1 is an excellent and broadly applicable alternative for D-luciferin, requiring significantly lower doses for in vivo bioluminescent imaging in rodent models of leishmaniasis and African trypanosomiasis.
Testing the Utility of Polygenic Risk Scores for Type 2 Diabetes and Obesity in Predicting Metabolic Changes in a Prediabetic Population: An Observational Study
Authors: Padilla-Martinez Felipe , Szczerbiński Łukasz , Citko Anna , Czajkowski Marcin , Konopka Paulina , Paszko Adam , Wawrusiewicz-Kurylonek Natalia , Górska Maria , Kretowski Adam
Published: December 2022

Prediabetes is an intermediate state of hyperglycemia during which glycemic parameters are above normal levels but below the T2D threshold. T2D and its precursor prediabetes affect 6.28% and 7.3% of the world’s population, respectively. The main objective of this paper was to create and compare two polygenic risk scores (PRSs) versus changes over time (Δ) in metabolic parameters related to prediabetes and metabolic complications. The genetics of 446 prediabetic patients from the Polish Registry of Diabetes cohort were investigated. Seventeen metabolic parameters were measured and compared at baseline and after five years using statistical analysis. Subsequently, genetic polymorphisms present in patients were determined to build a T2D PRS (68 SNPs) and an obesity PRS (21 SNPs). Finally, the association among the two PRSs and the Δ of the metabolic traits was assessed. After a multiple linear regression with adjustment for age, sex, and BMI at a nominal significance of (p < 0.05) and adjustment for multiple testing, the T2D PRS was found to be positively associated with Δ fat mass (FM) (p = 0.025). The obesity PRS was positively associated with Δ FM (p = 0.023) and Δ 2 h glucose (p = 0.034). The comparison of genotype frequencies showed that AA genotype carriers of rs10838738 were significantly higher in Δ 2 h glucose and in Δ 2 h insulin. Our findings suggest that prediabetic individuals with a higher risk of developing T2D experience increased Δ FM, and those with a higher risk of obesity experience increased Δ FM and Δ two-hour postprandial glucose. The associations found in this research could be a powerful tool for identifying prediabetic individuals with an increased risk of developing T2D and obesity.
The Effects of One-Point Mutation on the New Delhi Metallo Beta-Lactamase-1 Resistance toward Carbapenem Antibiotics and β-Lactamase Inhibitors: An In Silico Systematic Approach
Authors: Tran Van-Thanh , Tran Viet-Hung , Nguyen Dac-Nhan , Do Tran-Giang-Son , Vo Thanh-Phuong , Nguyen Thi-Thao-Nhung , Huynh Phuong Nguyen Hoai , Thai Khac-Minh
Published: December 2022

Antibiotic resistance has been becoming more and more critical due to bacteria’s evolving hydrolysis enzymes. The NDM-1 enzyme could hydrolyze not only carbapenems but also most of β-lactam’s antibiotics and inhibitors. In fact, variant strains could impose a high impact on the resistance of bacteria producing NDM-1. Although previous studies showed the effect of some variants toward antibiotics and inhibitors binding, there has been no research systematically evaluating the effects of alternative one-point mutations on the hydrolysis capacity of NDM-1. This study aims to identify which mutants could increase or decrease the effectiveness of antibiotics and β-lactamase inhibitors toward bacteria. Firstly, 35 different variants with a high probability of emergence based on the PAM-1 matrix were constructed and then docked with 5 ligands, namely d-captopril, l-captopril, thiorphan, imipenem, and meropenem. The selected complexes underwent molecular dynamics simulation and free energy binding estimation, with the results showing that the substitutions at residues 122 and 124 most influenced the binding ability of NDM-1 toward inhibitors and antibiotics. The H122R mutant decreases the binding ability between d-captopril and NDM-1 and diminishes the effectiveness of this antibiotic toward Enterobacteriaceae. However, the H122R mutant has a contrary impact on thiorphan, which should be tested in vitro and in vivo in further experiments.
The Antioxidant and In Vitro Wound Healing Activity of Cotyledon orbiculata Aqueous Extract and the Synthesized Biogenic Silver Nanoparticles
Authors: Tyavambiza Caroline , Meyer Mervin , Wusu Adedoja Dorcas , Madiehe Abram Madimabe , Meyer Samantha
Published: December 2022

The synthesis of silver nanoparticles using biogenic methods, particularly plants, has led to the discovery of several effective nanoparticles. In many instances, plant-derived silver nanoparticles have been shown to have more activity than the plant extract which was used to synthesize the nanoparticles. Silver nanoparticles have been successfully synthesized using the medicinal plant, Cotyledon orbiculata. This is a shrub found in the Western Cape province of South Africa. It has a long history of use in traditional medicine in the treatment of wounds and skin infections. The C. orbiculata synthesized silver nanoparticles (Cotyledon-AgNPs) were reported to have good antimicrobial and anti-inflammatory activities; however, their wound-healing properties have not been determined. This study aimed to determine the wound healing activity of Cotyledon-AgNPs using the scratch assay. Gene expression studies were also done to determine the nanoparticles’ mechanism of action. The Cotyledon-AgNPs showed good antioxidant, growth-promoting and cell migration properties. Gene expression studies showed that the C. orbiculata water extract and Cotyledon-AgNPs promoted wound healing by upregulating genes involved in cell proliferation, migration and growth while downregulating pro-inflammatory genes. This confirms, for the first time that a water extract of C. orbiculata and silver nanoparticles synthesized from this extract are good wound-healing agents.
Structural and Functional Characterization of β−lytic Protease from Lysobacter capsici VKM B−2533T
Authors: Afoshin Alexey , Tishchenko Svetlana , Gabdulkhakov Azat , Kudryakova Irina , Galemina Inna , Zelenov Dmitry , Leontyevskaya Elena , Saharova Sofia , Leontyevskaya (Vasilyeva) Natalya
Published: December 2022

The crystal structure of the Lysobacter capsici VKM B−2533T β-lytic protease (Blp), a medicinally promising antimicrobial enzyme, was first solved. Blp was established to possess a folding characteristic of the M23 protease family. The groove of the Blp active site, as compared with that of the LasA structural homologue from Pseudomonas aeruginosa, was found to have amino acid differences. Biochemical analysis revealed no differences in the optimal reaction conditions for manifesting Blp and LasA bacteriolytic activities. At the same time, Blp had a broader range of action against living and autoclaved target cells. The results suggest that the distinction in the geometry of the active site and the charge of amino acid residues that form the active site groove can be important for the hydrolysis of different peptidoglycan types in target cells.
Dapagliflozin Prevents High-Glucose-Induced Cellular Senescence in Renal Tubular Epithelial Cells
Authors: Eleftheriadis Theodoros , Pissas Georgios , Filippidis Georgios , Efthymiadi Maria , Liakopoulos Vassilios , Stefanidis Ioannis
Published: December 2022

Gliflozins are a new class of antidiabetic drugs with renoprotective properties. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to high-glucose conditions in the presence or absence of dapagliflozin, we evaluated cellular senescence pathways. High glucose increased sodium–glucose cotransporter-2 (SGLT-2) expression and glucose consumption, enhancing reactive oxygen species production. The latter induced DNA damage, ataxia telangiectasia mutated kinase (ATM), and p53 phosphorylation. Stabilized p53 increased the cell cycle inhibitor p21, resulting in cell cycle arrest and increasing the cellular senescence marker beta-galactosidase (GLB-1). RPTECs under high glucose acquired a senescence-associated secretory phenotype, which was detected by the production of IL-1β, IL-8, and TGF-β1. By decreasing SGLT-2 expression and glucose consumption, dapagliflozin inhibited the above pathway and prevented RPTEC senescence. In addition, dapagliflozin reduced the cell cycle inhibitor p16 independently of the glucose conditions. Neither glucose concentration nor dapagliflozin affected the epithelial-to-mesenchymal transition when assessed with α-smooth muscle actin (α-SMA). Thus, high glucose induces p21-dependent RPTEC senescence, whereas dapagliflozin prevents it. Since cellular senescence contributes to the pathogenesis of diabetic nephropathy, delineating the related molecular mechanisms and the effects of the widely used gliflozins on them is of particular interest and may lead to novel therapeutic approaches.
Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model
Authors: Motoji Yusuke , Fukazawa Ryuji , Matsui Ryosuke , Abe Yoshinori , Uehara Ikuno , Watanabe Makoto , Hashimoto Yoshiaki , Miyagi Yasuo , Nagi-Miura Noriko , Tanaka Nobuyuki , Ishii Yosuke
Published: December 2022

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE−) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.