bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Additional Cavity Floor Injection on the Ignition and Combustion Processes in a Mach 2 Supersonic Flow
Authors: Li Fan , Sun Mingbo , Cai Zun , Chen Yong , Sun Yongchao , Li Fei , Zhu Jiajian
Published: September 2020

Effects of additional cavity floor injection on the ethylene ignition and combustion processes in a cavity-based scramjet combustor are investigated experimentally in a Mach 2.0 supersonic flow using flame luminosity and CH* (CH radical) spontaneous emission methods and static pressure measurements. Numerical calculation is performed to study the non-reacting flow-field structures prior to ignition. Two injection schemes, including the cavity upstream injection scheme and the combined injection scheme with an additional cavity floor injection, are compared to study the effects of the additional cavity floor injection on the ignition and combustion processes. It is found that there exists an equivalence ratio upper limit for maintaining stable combustion for the cavity upstream injection scheme. As the equivalence ratio further increases, the fuel jet penetration is improved accordingly, and thus, the interaction between the fuel jet and the cavity is weakened, which can lead to the ignition failure and flame blowout during combustion. On the contrary, although the combined injection scheme has a minor effect on combustion enhancement at the same global equivalence ratio, it can also provide a more favorable flow-field environment that enables more successful ignitions and better flame stabilizations. For the combined injection scheme, as the equivalence ratio increases, the initial flame propagations are observed to perform different routines during the ignition process, and the major combustion reaction zone tends to move further downstream the cavity shear layer. It is concluded that the advantages of the combined injection scheme with an additional cavity floor injection are more significant when the equivalence ratio is higher, as well as that the interaction between the fuel jet and the cavity becomes weaker.
Comparison of Phenolic Compounds, Carotenoids, Amino Acid Composition, In Vitro Antioxidant and Anti-Diabetic Activities in the Leaves of Seven Cowpea (Vigna unguiculata) Cultivars
Authors: Moloto Mapula R. , Phan Anh Dao T. , Shai Jerry L. , Sultanbawa Yasmina , Sivakumar Dharini
Published: September 2020

Cowpea is a well-known nutrition rich African leafy vegetable that has potential to sustain food and nutrition insecurity in sub-Saharan Africa. Consumption of cowpea legumes is associated with reduced risk of type 2 diabetes mellitus. Therefore, the present study was designed to evaluate the (i) variation in phenolic metabolites in seven cowpea cultivars (VOP1, VOP2, VOP3, VOP4, VOP5, VOP7, and VOP8 using UHPLC coupled with high resolution Q-TOF-MS technique, (ii) in vitro antioxidant activity using ferric reducing/antioxidant capacity (FRAP) assay (iii) in vitro anti-diabetic effects and (iv) composition of carotenoids and amino acids of theses cowpea cultivars. The results of this study demonstrated that gentisic acid 5-O-glucoside, quercetin 3-(2G-xylosylrutinoside) and Quercetin 3-glucosyl-(1->2)-galactoside were highest in VOP1 VOP4 and VOP5, respectively. High inhibition (>50%) of α-glucosidase and α-amylase activities was shown by the leaf extracts (50 and 25 mg/mL) of VOP1 and VOP4. Cowpea cultivars VOP1 and VOP4 demonstrated the highest gene expression levels of regulation of glucose transporter GLUT4 in C2C12 skeletal muscle cells, similar to insulin. A positive correlation exited between the phenolic components and the inhibitory effect of antidiabetic enzymes and FRAP activity. Cytotoxic effect was not detected in vitro in any cowpea cultivar. Lutein (124.6 mg/100 g) and all-trans-beta-carotene (92.6 mg/100 g) levels were highest in VOP2 and VOP1, respectively. Cowpea cultivars VOP3 and VOP4 showed potential to fulfil the daily requirements of essential amino acids. Thus, based on this information, cowpea (leaves) genotypes/cultivars can be selected and propagated for the further development of supplementary foods or functional food ingredients.
Large-Scale Cloning and Comparative Analysis of TaNAC Genes in Response to Stripe Rust and Powdery Mildew in Wheat (Triticum aestivum L.)
Authors: Lv Shikai , Guo Huan , Zhang Min , Wang Qiaohui , Zhang Hong , Ji Wanquan
Published: September 2020

The NAM, ATAF1/2, and CUC2 (NAC) transcription factors (TFs) constitute the largest plant-specific TF superfamily, and play important roles in various physiological processes, including stress responses. Stripe rust and powdery mildew are the most damaging of the fungal diseases that afflict wheat (Triticum aestivum L.). However, studies on Triticum aestivum NAC (TaNAC)s’ role in resistance to the two diseases are still limited, especially in an overall comparative analysis of TaNACs responding or not to fungal stress. In the present study, 186 TaNAC transcripts were obtained from the resistant hexaploid wheat line N9134 under fungal stress, and 180 new transcripts were submitted to GenBank. Statistical results show that 35.1% (54/154) of TaNAC genes responded to stripe rust and powdery mildew in the seedling stage. “Abnormal” coding transcripts of differentially expressed (DE)-TaNAC genes in wheat responding to fungal stress were found in a significantly higher proportion (24/117 vs. 8/69, p = 0.0098) than in non-DE-NACs. This hinted that the alternative splicing of TaNAC genes was active in transcriptional or post-transcriptional regulation during plant-pathogen interactions. Full-length NAC proteins were classified into nine groups via phylogenetic analysis. Multiple-sequence alignment revealed diversity in the C-terminal structural organization, but the differentially expressed gene (DEG)-encoding proteins enriched in Subgroups VI and VII were conserved, with WV[L/V]CR amino acid residues in Motif 7 following the NAM domain. Our data that showed TaNAC TFs responded to fungal disease, which was affected by expression levels and by the regulation of multifarious transcript variants. These data for TaNAC responses to stripe rust and/or powdery mildew and their numerous structural variants provide a good resource for NAC function–mechanism analysis in the context of biotic-stress tolerance in wheat.
Mortality Rate and Predictors of Mortality in Hospitalized COVID-19 Patients with Diabetes
Authors: Acharya Dilaram , Lee Kwan , Lee Dong Seok , Lee Yun Sik , Moon Seong-Su
Published: September 2020

Studies have confirmed COVID-19 patients with diabetes are at higher risk of mortality than their non-diabetic counterparts. However, data-driven evidence of factors associated with increased mortality risk among hospitalized COVID-19 patients with diabetes is scarce in South Korea. This study was conducted to determine the mortality rate and identify risk factors of mortality among hospitalized COVID-19 patients with type 2 diabetes in Gyeongsangbuk-do province, South Korea. In this hospital-based, cross-sectional study, we enrolled a total of 324 patients with confirmed COVID-19, hospitalized at two of the tertiary level healthcare facilitates of Gyeongsangbuk-do, South Korea from 18 February to 30 June 2020. Demographic and clinical data and laboratory profiles were analyzed and multivariate logistic regression analysis was used to identify risk factors of mortality among diabetic patients with COVID-19. Of the 324 patients, 55 (16.97%) had diabetes mellitus. The mean age of all study subjects was 55 years, and the mean age of those with diabetes was greater than that of those without (69.8 years vs. 51.9 years). Remarkably, the mortality rate was much higher among those with diabetes (20.0% vs. 4.8%). Multivariate logistic regression analysis revealed that an older age (≥70 years) and a high serum lactate dehydrogenase (LDH) levels significantly predicted mortality among hospitalized COVID-19 patients with diabetes. Our study cautions more attention to be paid to patients with diabetes mellitus hospitalized for COVID-19, especially those aged ≥ 70 years and those with a high serum LDH level, to reduce the risk of mortality.
Education, Smoking and CRP Genetics in Relation to C-Reactive Protein Concentrations in Black South Africans
Authors: Myburgh Pieter Hermanus , Nienaber-Rousseau Cornelie , Kruger Iolanthé Marike , Towers Gordon Wayne
Published: September 2020

Because elevated circulating C-reactive protein (CRP) and low socio-economic status (SES), have both been implicated in cardiovascular disease development, we investigated whether SES factors associate with and interact with CRP polymorphisms in relation to the phenotype. Included in the study were 1569 black South Africans for whom CRP concentrations, 12 CRP single nucleotide polymorphisms (SNPs), cardiovascular health markers, and SES factors were known. None of the investigated SES aspects was found to associate with CRP concentrations when measured individually; however, in adjusted analyses, attaining twelve or more years of formal education resulted in a hypothetically predicted 18.9% lower CRP concentration. We also present the first evidence that active smokers with a C-allele at rs3093068 are at an increased risk of presenting with elevated CRP concentrations. Apart from education level, most SES factors on their own are not associated with the elevated CRP phenotype observed in black South Africans. However, these factors may collectively with other environmental, genetic, and behavioral aspects such as smoking, contribute to the elevated inflammation levels observed in this population. The gene-smoking status interaction in relation to inflammation observed here is of interest and if replicated could be used in at-risk individuals to serve as an additional motivation to quit.
Optimization of Cadmium Adsorption by Magnetic Graphene Oxide Using a Fractional Factorial Design
Authors: Wang Hui , Zhou Yiming , Hu Xinjiang , Guo Yuan , Cai Xiaoxi , Liu Chunjie , Wang Ping , Liu Yunguo
Published: September 2020

Graphene materials have attracted increasing interest in water remediation. In this study, magnetic graphene oxide (MGO) was prepared through the modified Hummers method and the adsorption behaviors of cadmium were investigated. Firstly, the sorption kinetics, isotherms, as well as the effects of pH were investigated. Then, fractional factorial design (FFD) was used to optimize the effects of pH, temperature, time, initial concentration of cadmium ion and NaCl on cadmium adsorption. The results indicate that MGO could effectively remove cadmium ions from an aqueous solution and the sorption data could be described well by pseudo-second-order and Freundlich models, showing that the adsorption rate of cadmium ions on MGO is multilayer adsorption and dominated by the chemical adsorption. According to the FFD results, the maximum adsorption capacity of cadmium ions was 13.169 mg/g under the optimum condition of pH value 8, 45 °C, contact time 60 min, initial cadmium concentration of 70 mg/L and NaCl concentration of 100 mg/L. Higher levels of the pH value, temperature and initial cadmium concentration are beneficial to the adsorption process. These results are important for estimating and optimizing the removal of metal ions by MGO composite.
Compliance with the Framework Convention on Tobacco Control in Slovakia and in Finland: Two Different Worlds
Authors: Pavlikova Barbara , Freel Lenka , van Dijk Jitse P.
Published: September 2020

The Framework Convention on Tobacco Control (FCTC) developed by the State Parties to the World Health Organization was ratified in Slovakia in 2004 and in Finland in 2005. The aim of this study was to explore and compare compliance with the FCTC in Finland and Slovakia. This is a two-country comparative study of tobacco control policy based on implementation of the FCTC in Slovakia and Finland. Compliance with the FCTC was measured similarly in Slovakia and Finland in terms of their institutional structure supporting a smoking free environment and implementation of selected articles of the FCTC. In Finland the responsibilities for anti-tobacco policy are clearly assigned. Slovakia does not have specifically responsible institutions. Finland has a clear plan for achieving the goal of a smoking-free country based on empirical evidence. Slovakia meets only the minimum standard resulting from its commitment as ratified in the FCTC and data are out of date or missing completely.
Factors Associated with the Health Literacy on Social Determinants of Health: A Focus on Socioeconomic Position and Work Environment
Authors: Cho Mikyeong , Lee Young-Me , Lim Seung joo , Lee Hyeonkyeong
Published: September 2020

Though impressive progress has been made in healthcare worldwide, many people still experience disproportionate health burdens and inequities in healthcare services. For establishing sustainable development goals, health literacy on social determinants of health (HL-SDH) has been recognized as a key to creating better social and physical environments. In particular, low levels of health literacy among industrial workers are considered as a major barrier to benefitting from the progress made in healthcare. This study aimed to describe levels of HL-SDH and to examine the relationships among socioeconomic status, working environment, and HL-SDH among workers in Korea. A total of 660 workers from an online panel participated in Korea from 30 May to 7 June 2018. The Korean version of HL-SDH instrument consisted of 33 items and four dimensions: access, understand, appraise, and apply. Descriptive statistics, a t-test, ANOVA, and multiple regression analysis were conducted. The mean score of HL-SDH was 2.48. Perceived mental health status, annual income, and the number of employees per worksite were found to be statistically significant factors related to HL-SDH (F = 3.64, p = <0.001). The HL-SDH score was considerably higher, indicating that nursing interventions to enhance HL-SDH are required for health promotion, especially among workers in poor social and working environments.
Combined Toxicity of Cannabidiol Oil with Three Bio-Pesticides against Adults of Sitophilus Zeamais, Rhyzopertha Dominica, Prostephanus Truncatus and Trogoderma Granarium
Authors: Mantzoukas Spiridon , Kalyvas Nikolaos , Ntoukas Aristeidis , Lagogiannis Ioannis , Farsalinos Konstantinos , Eliopoulos Panagiotis A. , Poulas Konstantinos
Published: September 2020

The present study investigates the interaction between cannabidiol (CBD) oil and three biopesticides: Azatin and two baculovirus formulations (Madex and Helicovex), both separately and in combination, in order to investigate their interaction against adults of four major coleopteran stored-product pests: Sitophilus zeamais (Coleoptera: Curculionidae), Rhyzopertha dominica (Coleoptera: Bostrichidae), Prostephanus truncatus (Coleoptera: Bostrichidae) and Trogoderma granarium (Coleoptera: Dermestidae). CBD, which has been understudied for its insecticidal properties, was applied at three different doses (500, 1500 and 3000 ppm). The biopesticides were administered at 1500 ppm. Interactions in the combined treatments were mathematically estimated as not synergistic and mostly competitive except for the combined treatments of CBD (1500 and 3000 ppm) with Azatin (1500 ppm) which were marked by an additive interaction. In its individual application, CBD oil generated the highest insect mortality while its effect was clearly dose-dependent. The findings reveal a promising effect of CBD oil against these coleopterans which had not been previously tested together.
Temporal Kinematic Differences between Forward and Backward Jump-Landing
Authors: Xu Datao , Cen Xuanzhen , Wang Meizi , Rong Ming , István Bíró , Baker Julien S. , Gu Yaodong
Published: September 2020

Backward jump-landing during sports performance will result in dynamic postural instability with a greater risk of injury, and most research studies have focused on forward landing. Differences in kinematic temporal characteristics between single-leg and double-leg backward jump-landing are seldom researched and understood. The purpose of this study was to compare and analyze lower extremity kinematic differences throughout the landing phases of forward and backward jumping using single-leg and double-leg landings (FS and BS, FD and BD). Kinematic data were collected during the landing phases of FS and BS, FD and BD in 45 participants. Through statistical parametric mapping (SPM) analysis, we found that the BS showed smaller hip and knee flexion and greater vertical ground reactive force (VGRF) than the FS during 0–37.42% (p = 0.031), 16.07–32.11% (p = 0.045), and 23.03–17.32% (p = 0.041) landing phases. The BD showed smaller hip and knee flexion than the FD during 0–20.66% (p = 0.047) and 0–100% (p < 0.001) landing phases. Most differences appeared within a time frame during the landing phase at 30–50 ms in which non-contact anterior cruciate ligament (ACL) injuries are thought to occur and are consistent with the identification of risk in biomechanical analysis. A landing strategy that consciously increases the knee and hip flexion angles during backward landing should be considered for people as a measure to avoid injury during the performance of this type of physical activity.
Living with Pain and Looking for a Safe Environment: A Qualitative Study among Nursing Students with Dysmenorrhea
Authors: Fernández-Martínez Elia , Abreu-Sánchez Ana , Pérez-Corrales Jorge , Ruiz-Castillo Javier , Velarde-García Juan Francisco , Palacios-Ceña Domingo
Published: September 2020

Dysmenorrhea refers to chronic pain associated with menstruation that is often accompanied by other symptoms. Primary dysmenorrhea (PD) occurs without any associated pelvic disease. Nonetheless, it may negatively affect women’s quality of life. Among university students, dysmenorrhea decreases academic performance and is a cause of absenteeism. The purposes of our study were to describe how nursing students experienced PD and the changes affecting their body and mood. A qualitative case study was performed among 33 nursing students with PD. Data were collected through five focus groups (with two sessions each) and 10 researchers’ field notes. We used a video meeting platform to conduct the focus groups. A thematic analysis was performed, and the Standards for Reporting Qualitative Research and the Consolidated Criteria for Reporting Qualitative Research guidelines were followed. Three main themes emerged from the data: (a) living with dysmenorrhea, with two subthemes: menstruation and pain; (b) body changes and mood swings; and (c) seeking a safe environment, with three subthemes: safe environment, unsafe environment, and key safety aspects. Students considered menstruation to be negative and limiting, causing physical and mood changes, making them feel less attractive, and conditioning their way of dressing and relating.
Novel Coronavirus (COVID-19) Knowledge, Precaution Practice, and Associated Depression Symptoms among University Students in Korea, China, and Japan
Authors: Zhao Bo , Kong Fanlei , Aung Myo Nyein , Yuasa Motoyuki , Nam Eun Woo
Published: September 2020

This study assessed university students’ knowledge and precaution practices of Novel Coronavirus (COVID-19) in South Korea, China, and Japan, and investigated their depressive states during the pandemic. This cross-sectional survey collected data from 821 respondents, using an anonymous online questionnaire designed by the Yonsei Global Health Center, from 23 March to 20 April 2020, which included socio-demographic questions, knowledge and perceptions of COVID-19, preventative practices, and the Patient Health Questionnaire-9 (PHQ-9) scale to assess mental health. High proportions of respondents showed good knowledge of the transmission pathways and information related to COVID-19. Contact history as well as concerns about family members and the disease showed statistically significant distinctions by nationality and gender. On the whole, all participants reported good levels of preventative practices. The Chinese group reported the highest preventative practice scores; and females scored higher than males. Moreover, the Japanese group showed the most severe depressive states; overall, females experienced more severe depression than males. Thus, authorities should especially emphasize the importance of COVID-19 precautions to males. Educational departments and health authorities should observe the mental health of university adults during the pandemic and plan interventions to improve it.
The Effect of Swimming on Anxiety-Like Behaviors and Corticosterone in Stressed and Unstressed Rats
Authors: Safari Mohammad Amin , Koushkie Jahromi Maryam , Rezaei Rasoul , Aligholi Hadi , Brand Serge
Published: September 2020

This study assessed the effect of swimming training on anxiety-like behaviors and corticosterone. Thirty adult male Wistar rats were randomly assigned to five study conditions: swimming training (ST); exposure to chronic mild stress (CS); exposure to chronic mild stress followed by swimming training (CS + ST); exposure to chronic mild stress followed by a recovery period (CS + recovery); control. The exercise training consisted of 60 min of swimming exercise per day, for five days a week, and four consecutive weeks. A chronic mild stress program (CMS) was applied for a period of four weeks. Anxiety-like behaviors were measured by open field test (OFT). The number of excrements and blood corticosterone were used as physiological parameters of anxiety. To assess corticosterone, blood samples were taken 48 h after the last session of experiments. Compared to other study conditions, the lowest anxiety-like behaviors and corticosterone concentrations were observed in the ST condition in unstressed rats. In stressed rats, as in the ST + CS group, swimming training probably reduced some anxiety behaviors, but the results showed increased corticosterone compared to control and CS + Recovery. Anxiety parameters and corticosterone concentrations were greatest in the CS condition. In the ST group, anxiety parameters were less than for the ST + CS group. In the CS + Recovery group, anxiety parameters were less than for the CS group. In summary, self-paced swimming training could attenuate some anxiety parameters in both stressed and non-stressed rats. The effect of swimming training in unstressed rats was more prominent than in stressed rats. In stressed rats, a period of recovery was more effective than swimming training in reducing corticosterone. Mechanisms of anxiety reduction other than cortisol should be investigated in future research.
Does the Effect of Internet Use on Chinese Citizens’ Psychological Well-Being Differ Based on Their Hukou Category?
Authors: Long Cuihong , Han Jiajun , Yi Chengzhi
Published: September 2020

This paper draws support from the 2018 wave of the China Family Panel Studies (CFPS 2018) and uses unconditional quantile regression, re-centered influence function (RIF) decomposition, linear structural equation modelling, extended regression modelling and censored regression to explore the heterogeneity of the impact of Internet use on the psychological well-being of Chinese non-agricultural and agricultural hukou holders. We find that Internet use better improves the psychological well-being of non-agricultural hukou holders, thereby widening the gap in psychological well-being between urban and rural residents in China. Through RIF decomposition, we observe that, except for the 10th quantile, the expansion effect of Internet use on the inequality in psychological well-being between agricultural and non-agricultural hukou holders is mainly reflected in the structure effect, which shows that compared to non-agricultural hukou holders, the return rate of Internet use on the psychological well-being of agricultural hukou holders is lower. Further mechanism analysis shows that using the Internet to socialize, obtain information and understand politics is more beneficial for the psychological well-being of non-agricultural hukou holders; moreover, Internet use can further exert different effects on the psychological well-being of the two groups by differently influencing their job satisfaction, government evaluation, and sleep quality. This study also confirms that relying only on external scientific and technological progress has a limited corrective effect on existing inequalities.
Application of Activity Trackers among Nursing Home Residents—A Pilot and Feasibility Study on Physical Activity Behavior, Usage Behavior, Acceptance, Usability and Motivational Impact
Authors: Auerswald Tina , Meyer Jochen , von Holdt Kai , Voelcker-Rehage Claudia
Published: September 2020

The aim of this study was to assess physical activity and sedentary behavior, as well as the usage behavior, usability, acceptance, and motivational impact of an applied activity tracker among nursing home residents. Physical activity and usage behavior were measured among 22 residents (68 to 102 years) by use of a commercial activity tracker worn during waking hours for 77 days on average. Usability, acceptance, and motivational impact of the tracker were examined using an adapted questionnaire. Participants walked, on average, 1007 ± 806 steps per day and spent, on average, more than 9 h (77.2% of their waking time) sedentary. The average steps/day increased significantly within the first five weeks of wearing the activity tracker. The acceptance rate was high (94.4%). The tracker was used for 65.4% of the individual study period, and usage behavior did not significantly change during the first five wearing weeks. Participants with a usage time of ≥50% walked significantly more steps per day than those with a lower usage. Overall, we were able to reveal that the residents were highly inactive and sedentary. The results support the feasibility of a long-term application of activity trackers to assess or even increase physical activity behavior.
Betel Quid Health Risks of Insulin Resistance Diseases in Poor Young South Asian Native and Immigrant Populations
Authors: de la Monte Suzanne M. , Moriel Natalia , Lin Amy , Abdullah Tanoukhy Nada , Homans Camille , Gallucci Gina , Tong Ming , Saito Ayumi
Published: September 2020

Betel quid, traditionally prepared with areca nut, betel leaf, and slaked lime, has been consumed for thousands of years, mainly in the form of chewing. Originally used for cultural, medicinal, and ceremonial purposes mainly in South Asian countries, its use has recently spread across the globe due to its psychoactive, euphoric, and aphrodisiac properties. Now it is widely used as a social lubricant and source of financial profit. Unfortunately, the profit motive has led to high rates of habitual consumption with eventual conversion to addiction among young girls and boys. Moreover, the worrisome practice of including tobacco in quid preparations has grown, particularly among pregnant women. Major health concerns include increased rates of malignancy, oral pathology, and cardiovascular, hepatic, fertility, metabolic, and neuropsychiatric disorders. Metabolic disorders and insulin resistance disease states such as type 2 diabetes, obesity, and metabolic syndrome contribute to cognitive decline and neurodegeneration. Mechanistically, the constituents of areca nut/betel quid are metabolized to N-nitroso compounds, i.e., nitrosamines, which are carcinogenic at high doses and cause insulin resistance following chronic low-level exposures. From an epidemiological perspective, the rising tide of insulin resistance diseases including obesity, diabetes, and dementias that now disproportionately burden poor countries has been propagated by rapid commercialization and enhanced access to betel quid. Public health measures are needed to impose socially and ethically responsible barriers to yet another cause of global health disparity.
The Role of Sirtuins in Kidney Diseases
Authors: Hong Yu Ah , Kim Ji Eun , Jo Minjee , Ko Gang-Jee
Published: September 2020

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.
p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation
Authors: Sun Chiao-Yin , Li Jian-Ri , Wang Ya-Yu , Lin Shih-Yi , Ou Yen-Chuan , Lin Cheng-Jui , Wang Jiaan-Der , Liao Su-Lan , Chen Chun-Jung
Published: September 2020

Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDNF) and serotonin were decreased in association with increased corticosterone and repressor element-1 silencing transcription factor (REST), regulators involved in neurological disorders. On the contrary, these PCS-induced changes were alleviated by uremic toxin absorbent AST-120. Taken together, PCS administration in mice with nephrectomy contributed to neurological disorders with increased oxidative stress and neuroinflammation, which were alleviated by PCS chelation. It is suggested that PCS may be a therapeutic target for chronic kidney disease-associated CNS diseases.
Formation and Recognition of UV-Induced DNA Damage within Genome Complexity
Authors: Johann to Berens Philippe , Molinier Jean
Published: September 2020

Ultraviolet (UV) light is a natural genotoxic agent leading to the formation of photolesions endangering the genomic integrity and thereby the survival of living organisms. To prevent the mutagenetic effect of UV, several specific DNA repair mechanisms are mobilized to accurately maintain genome integrity at photodamaged sites within the complexity of genome structures. However, a fundamental gap remains to be filled in the identification and characterization of factors at the nexus of UV-induced DNA damage, DNA repair, and epigenetics. This review brings together the impact of the epigenomic context on the susceptibility of genomic regions to form photodamage and focuses on the mechanisms of photolesions recognition through the different DNA repair pathways.
Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer
Authors: Capone Francesca , Polo Andrea , Sorice Angela , Budillon Alfredo , Costantini Susan
Published: September 2020

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.
Nasal Immunization with the C-Terminal Domain of Bcla3 Induced Specific IgG Production and Attenuated Disease Symptoms in Mice Infected with Clostridioides difficile Spores
Authors: Maia Ana Raquel , Reyes-Ramírez Rodrigo , Pizarro-Guajardo Marjorie , Saggese Anella , Ricca Ezio , Baccigalupi Loredana , Paredes-Sabja Daniel
Published: September 2020

Clostridioides difficile is a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance an immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets for new therapies. In this context, spore surface proteins of C. difficile, are potential antigens for the development of vaccines targeting C. difficile spores. Here, we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced in Escherichia coli and tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTD was also exposed on the surface of B. subtilis spores, a mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTD induced antibody production in mice and attenuated some C. difficile infection symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization routes need to be optimized, our results suggest BclA3CTD as a potentially effective antigen to develop a new vaccination strategy targeting C. difficile spores.
Anti-PD-1 Therapy Does Not Influence Hearing Ability in the Most Sensitive Frequency Range, but Mitigates Outer Hair Cell Loss in the Basal Cochlear Region
Authors: Szepesy Judit , Miklós Gabriella , Farkas János , Kucsera Dániel , Giricz Zoltán , Gáborján Anita , Polony Gábor , Szirmai Ágnes , Tamás László , Köles László , Varga Zoltán V. , Zelles Tibor
Published: September 2020

The administration of immune checkpoint inhibitors (ICIs) often leads to immune-related adverse events. However, their effect on auditory function is largely unexplored. Thorough preclinical studies have not been published yet, only sporadic cases and pharmacovigilance reports suggest their significance. Here we investigated the effect of anti-PD-1 antibody treatment (4 weeks, intraperitoneally, 200 μg/mouse, 3 times/week) on hearing function and cochlear morphology in C57BL/6J mice. ICI treatment did not influence the hearing thresholds in click or tone burst stimuli at 4–32 kHz frequencies measured by auditory brainstem response. The number and morphology of spiral ganglion neurons were unaltered in all cochlear turns. The apical-middle turns (<32 kHz) showed preservation of the inner and outer hair cells (OHCs), whilst ICI treatment mitigated the age-related loss of OHCs in the basal turn (>32 kHz). The number of Iba1-positive macrophages has also increased moderately in this high frequency region. We conclude that a 4-week long ICI treatment does not affect functional and morphological integrity of the inner ear in the most relevant hearing range (4–32 kHz; apical-middle turns), but a noticeable preservation of OHCs and an increase in macrophage activity appeared in the >32 kHz basal part of the cochlea.
Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1
Authors: Kim Geon-Hee , Fang Xue-Quan , Lim Woo-Jin , Park Jooho , Kang Tae-Bong , Kim Ji Hyung , Lim Ji-Hong
Published: September 2020

Constitutive activation of the β-catenin dependent canonical Wnt signaling pathway, which enhances tumor growth and progression in multiple types of cancer, is commonly observed in melanoma. LEF1 activates β-catenin/TCF4 transcriptional activity, promoting tumor growth and progression. Although several reports have shown that LEF1 is highly expressed in melanoma, the functional role of LEF1 in melanoma growth is not fully understood. While A375, A2058, and G361 melanoma cells exhibit abnormally high LEF1 expression, lung cancer cells express lower LEF1 levels. A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed β-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression. Cinobufagin decreases LEF1 expression in a dose-dependent manner and Wnt/β-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines. Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells. In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells. Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/β-catenin signaling via LEF1 inhibition.
Influence of Hydroxyapatite Surface Functionalization on Thermal and Biological Properties of Poly(l-Lactide)- and Poly(l-Lactide-co-Glycolide)-Based Composites
Authors: Gazińska Małgorzata , Krokos Anna , Kobielarz Magdalena , Włodarczyk Marcin , Skibińska Paulina , Stępak Bogusz , Antończak Arkadiusz , Morawiak Milena , Płociński Przemysław , Rudnicka Karolina
Published: September 2020

Novel biocomposites of poly(L-lactide) (PLLA) and poly(l-lactide-co-glycolide) (PLLGA) with 10 wt.% of surface-modified hydroxyapatite particles, designed for applications in bone tissue engineering, are presented in this paper. The surface of hydroxyapatite (HAP) was modified with polyethylene glycol by using l-lysine as a linker molecule. The modification strategy fulfilled two important goals: improvement of the adhesion between the HAP surface and PLLA and PLLGA matrices, and enhancement of the osteological bioactivity of the composites. The surface modifications of HAP were confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), TGA, and elemental composition analysis. The influence of hydroxyapatite surface functionalization on the thermal and in vitro biological properties of PLLA- and PLLGA-based composites was investigated. Due to HAP modification with polyethylene glycol, the glass transition temperature of PLLA was reduced by about 24.5 °C, and melt and cold crystallization abilities were significantly improved. These achievements were scored based on respective shifting of onset of melt and cold crystallization temperatures and 1.6 times higher melt crystallization enthalpy compared with neat PLLA. The results showed that the surface-modified HAP particles were multifunctional and can act as nucleating agents, plasticizers, and bioactive moieties. Moreover, due to the presented surface modification of HAP, the crystallinity degree of PLLA and PLLGA and the polymorphic form of PLLA, the most important factors affecting mechanical properties and degradation behaviors, can be controlled.
Doubly-Charged Negative Ions as Novel Tunable Catalysts: Graphene and Fullerene Molecules Versus Atomic Metals
Authors: Suggs Kelvin , Msezane Alfred Z.
Published: September 2020

The fundamental mechanism underlying negative-ion catalysis involves bond-strength breaking in the transition state (TS). Doubly-charged atomic/molecular anions are proposed as novel dynamic tunable catalysts, as demonstrated in water oxidation into peroxide. Density Functional Theory TS calculations have found a tunable energy activation barrier reduction ranging from 0.030 eV to 2.070 eV, with Si2−, Pu2−, Pa2− and Sn2− being the best catalysts; the radioactive elements usher in new application opportunities. C602− significantly reduces the standard C60− TS energy barrier, while graphene increases it, behaving like cationic systems. According to their reaction barrier reduction efficiency, variation across charge states and systems, rank-ordered catalysts reveal their tunable and wide applications, ranging from water purification to biocompatible antiviral and antibacterial sanitation systems.
Impact of KLF4 on Cell Proliferation and Epithelial Differentiation in the Context of Cystic Fibrosis
Authors: Sousa Luís , Pankonien Ines , Simões Filipa B. , Chanson Marc , Amaral Margarida D.
Published: September 2020

Cystic fibrosis (CF) cells display a more cancer-like phenotype vs. non-CF cells. KLF4 overexpression has been described in CF and this transcriptional factor acts as a negative regulator of wt-CFTR. KLF4 is described as exerting its effects in a cell-context-dependent fashion, but it is generally considered a major regulator of proliferation, differentiation, and wound healing, all the processes that are also altered in CF. Therefore, it is relevant to characterize the differential role of KLF4 in these processes in CF vs. non-CF cells. To this end, we used wt- and F508del-CFTR CFBE cells and their respective KLF4 knockout (KO) counterparts to evaluate processes like cell proliferation, polarization, and wound healing, as well as to compare the expression of several epithelial differentiation markers. Our data indicate no major impact of KLF4 KO in proliferation and a differential impact of KLF4 KO in transepithelial electrical resistance (TEER) acquisition and wound healing in wt- vs. F508del-CFTR cells. In parallel, we also observed a differential impact on the levels of some differentiation markers and epithelial-mesencymal transition (EMT)-associated transcription factors. In conclusion, KLF4 impacts TEER acquisition, wound healing, and the expression of differentiation markers in a way that is partially dependent on the CFTR-status of the cell.
Recent Advances in Cell-Based Therapies for Ischemic Stroke
Authors: Suda Satoshi , Nito Chikako , Yokobori Shoji , Sakamoto Yuki , Nakajima Masataka , Sowa Kota , Obinata Hirofumi , Sasaki Kazuma , Savitz Sean I. , Kimura Kazumi
Published: September 2020

Stroke is the most prevalent cardiovascular disease worldwide, and is still one of the leading causes of death and disability. Stem cell-based therapy is actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types of cells, including bone marrow mononuclear cells, bone marrow mesenchymal stem cells, dental pulp stem cells, neural stem cells, inducible pluripotent stem cells, and genetically modified stem cells have been found to improve neurological outcomes in animal models of stroke, and there are some ongoing clinical trials assessing their efficacy in humans. In this review, we aim to summarize the recent advances in cell-based therapies to treat stroke.
The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
Authors: Ohiomokhare Samuel , Olaolorun Francis , Ladagu Amany , Olopade Funmilayo , Howes Melanie-Jayne R. , Okello Edward , Olopade James , Chazot Paul L.
Published: September 2020

Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)B9Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD.
Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia
Authors: Fabris Linda , Juracek Jaroslav , Calin George
Published: September 2020

The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent a heterogeneous group of transcripts, ranging from a few base pairs to several kilobases, that are able to regulate gene networks and intracellular pathways by interacting with DNA, transcripts or proteins. Deregulation of ncRNAs impinge on several cellular responses and can play a major role in each single hallmark of cancer. This review will focus on the most important short and long non-coding RNAs in chronic lymphocytic leukemia (CLL), highlighting their implications as potential biomarkers and therapeutic targets as they relate to the well-established hallmarks of cancer. The key molecular events in the onset of CLL will be contextualized, taking into account the role of the “dark matter” of the genome.