bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological and Psychological Responses of Viewing a Waterfall Image: A Crossover Study
Authors: Jo Hyunju , Ikei Harumi , Miyazaki Yoshifumi
Published: December 2022

Growing interest in the relaxation effect of nature has elicited demands for scientific verification of the various natural elements. This study investigated the physiological and psychological responses of 27 females in their 20 s to viewing a waterfall and urban images (control) presented via a large, high-resolution display for 90 s. High-frequency [HF] for parasympathetic nervous activity and the ratio of low-frequency (LF)/[LF + HF] for sympathetic nervous activity by heart rate variability and heart rate were recorded. Simultaneous changes in oxyhemoglobin concentration in the prefrontal cortex were recorded by near-infrared time-resolved spectroscopy. The modified semantic differential method and Profile of Mood States Second Edition were used to assess the psychological effects on the participants after viewing each image. The results showed that viewing the waterfall image, compared with viewing the urban image, (1) increased sympathetic nervous activity; (2) provided comfortable, relaxed, and natural impressions; (3) improved mood states. In conclusion, visual contact with a waterfall image physiologically activated sympathetic nervous activity and psychologically evoked positive moods and feelings.
Mediating Role of Emotional Intelligence in the Relationship between Anxiety Sensitivity and Academic Burnout in Adolescents
Authors: Gázquez Linares José Jesús , Molero Jurado María del Mar , Pérez-Fuentes María del Carmen , Martos Martínez África , Simón Márquez María del Mar
Published: December 2022

(1) Background: Increased stress and study overload during adolescence could be related to academic burnout. Anxiety sensitivity of students seems to affect burnout levels, while emotional intelligence enables emotion management under stressful conditions. The objective of this study is to analyze the roles of anxiety sensitivity and emotional intelligence in academic burnout. (2) Methods: In this quantitative cross-sectional study conducted in Spain, the sample comprised 1287 high school students aged 14 to 18 who filled out the Maslach Burnout Inventory-General Survey, the Spanish version adapted for high school students of the Anxiety Sensitivity Index-3, and Brief Emotional Intelligence Inventory. (3) Results: Anxiety sensitivity was significantly higher in cynicism and emotional exhaustion. Furthermore, the mediation analysis showed that high anxiety sensitivity directly affected student exhaustion, cynicism, and efficacy levels. These effects were mediated mainly through stress management but also through the effect of stress management on mood, both emotional intelligence factors. (4) Conclusions: The academic changes that occur during high school hinder engagement and performance. Promoting the development of emotional skills would enable young people to manage their emotions when they become overwhelming and diminish their lack of interest and exhaustion in the classroom.
Global Research Trends and Hotspots on Mitochondria in Acute Lung Injury from 2012–2021: A Bibliometric Analysis
Authors: Hu Song , Zhou Wenyu , Wang Sheng , Xiao Zhuoran , Li Quanfu , Zhou Huanping , Liu Meiyun , Deng Huimin , Wei Juan , Zhu Wanli , Yang Hao , Lv Xin
Published: December 2022

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with mitochondria and lacks effective preventive and therapeutic measures. This bibliometric study aims to gain insight into the scientific findings regarding mitochondria in ALI/ARDS. Methods: We retrieved the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) for mitochondria in ALI/ARDS publications from 2012–2021. VOSviewer, CiteSpace (5.8. R3) and Bibliometrix (3.1.4) R package were used for further analysis and visualization. Result: A total of 756 English-language articles and reviews were identified. The annual number of publications presented a rapidly developing trend. China was the most productive and cited country, and the USA had the greatest impact. In the keyword co-occurring network, the terms “acute lung injury”, “oxidative stress”, “inflammation”, “mitochondria” and “apoptosis” occurred most frequently. The co-citation network revealed that #1 mesenchymal stromal cell and #3 endothelial cell had the most bursts of citations. In addition, research hotspots have shifted from “potential therapeutic treatments” and “mitochondrial DNA (mtDNA)” to “endothelial cell” and “mesenchymal stromal cell (MSC)”. Conclusion: This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. mtDNA, mitophagy, and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years.
Job Satisfaction Mediates the Relationship between Psychosocial and Organization Factors and Mental Well-Being in Schoolteachers
Authors: Capone Vincenza , Joshanloo Mohsen , Sang-Ah Park Miriam
Published: December 2022

The study aimed to explore the associations between the psychosocial and organizational factors, job satisfaction, and mental well-being of schoolteachers. A further aim was to examine whether job satisfaction mediated the relationship between these factors and mental well-being. A cross-sectional design was used to collect data using a self-reported questionnaire. Six hundred and nine schoolteachers were included in the final analyses. The relationships between the variables were tested in a path analysis model. The data fit the hypothesized model well. The results demonstrated that organizational justice, efficacy beliefs, and school climate were significantly associated with job satisfaction and that the relationships between these variables and mental well-being were mediated by job satisfaction. The findings have implications for programs targeted at promoting teachers’ well-being.
Risk Assessment of Depression amongst Women during Menopause before and during the COVID-19 Pandemic
Authors: Kułak-Bejda Agnieszka , Krajewska-Ferishah Katarzyna , Szyszko-Perłowska Agnieszka , Waszkiewicz Napoleon
Published: December 2022

During menopause, the risk of depression is 2–5 times greater than pre- or post-menopause. To assess the risk of depression amongst menopausal women in 2006, compared with 2021 (i.e., during the COVID-19 pandemic), we recruited female volunteers at least 40 years old to complete the menopause rating scale (MRS), the Blatt–Kupperman menopausal index (BKMI), and the Beck depression inventory. Compared with 2006, in 2021, the number of participants who experienced mild, moderate, and severe menopausal symptoms rose by 8%, 1.9%, and 3.2%, respectively. Moreover, the frequency of using hormone replacement therapy rose by 5.1%, feelings of mistrust by 16%, feelings of guilt by 11%, disposition to cry by 25%, mood swings by 12%, and suicidal ideation by 9%, whilst the average body weight and body mass index fell by 5.1 kg and 2.3%, respectively. In 2006 and 2021, 46.3% and 59.3% of participants experienced moderate depression, whereas 3.0% and 5.2% experienced severe depression. The number of participants who denied needing support during menopause decreased by 14.6%, whereas the demand for support from husbands and friends increased by 18.3% and 9.8%, respectively. In 2021, the number of participants who experienced menopausal symptoms, a loss of trust, self-blame, a tendency to cry, mood swings, suicidal ideation, and anxiety also increased compared with 2006, whilst the number of participants without depressive symptoms decreased, but with suspected mild or severe depression increased. Last, menopausal complaints caused an increase in depressive mood in 2021, as evaluated using the BKMI and MRS.
Assessing Differences in Attitudes toward Occupational Safety and Health Measures for Infection Control between Office and Assembly Line Employees during the COVID-19 Pandemic in Germany: A Cross-Sectional Analysis of Baseline Data from a Repeated Employee Survey
Authors: Soeder Jana , Neunhöffer Anna T. , Wagner Anke , Preiser Christine , Rebholz Benjamin , Montano Diego , Schmitz Norbert , Kauderer Johanna , Papenfuss Falko , Klink Antje , Alsyte Karina , Rieger Monika A. , Rind Esther
Published: December 2022

In our study, we investigated possible differences across occupational groups regarding employees’ perceived work-related risk of infection with SARS-CoV-2, attitudes toward technical, organisational, and personal occupational safety and health (OSH) measures for infection control, and factors associated with this attitude. We analysed baseline data (10 August to 25 October 2020) from a repeated standardised online survey distributed at a worldwide leading global supplier of technology and services in Germany. 2144 employees (32.4% women; age (mean ± SD): 44 ± 11 years) who worked predominantly remotely (n = 358), at an on-site office (n = 1451), and assembly line/manufacturing (n = 335) were included. The work-related SARS-CoV-2 risk of infection differed between office employees working remotely and on-site (mean ± SD = 2.9 ± 1.5 vs. 3.2 ± 1.5; Mann-Whitney-U-Test: W = 283,346; p < 0.002; ε2 = 0.01) and between on-site office and assembly line/manufacturing employees (3.8 ± 1.7; W = 289,174; p < 0.001; ε2 = 0.02). Attitude scores toward technical OSH-measures differed between remote and on-site office (4.3 ± 0.5 vs. 4.1 ± 0.6; W = 216,787; p < 0.001; ε2 = 0.01), and between on-site office and assembly line/manufacturing employees (3.6 ± 0.9; W = 149,881; p < 0.001; ε2 = 0.07). Findings were similar for organisational and personal measures. Affective risk perception, COVID-19-specific resilience, and information about COVID-19-related risks were associated with the employees’ attitudes. To promote positive attitudes, it seems to be important to consider occupational-group-specific context factors when implementing OSH-measures for infection control.
A Hybrid Model for Coronavirus Disease 2019 Forecasting Based on Ensemble Empirical Mode Decomposition and Deep Learning
Authors: Liu Shidi , Wan Yiran , Yang Wen , Tan Andi , Jian Jinfeng , Lei Xun
Published: December 2022

Background: The novel coronavirus pneumonia that began to spread in 2019 is still raging and has placed a burden on medical systems and governments in various countries. For policymaking and medical resource decisions, a good prediction model is necessary to monitor and evaluate the trends of the epidemic. We used a long short-term memory (LSTM) model and the improved hybrid model based on ensemble empirical mode decomposition (EEMD) to predict COVID-19 trends; Methods: The data were collected from the Harvard Dataverse. Epidemic data from 21 January 2020 to 25 April 2021 for California, the most severely affected state in the United States, were used to develop an LSTM model and an EEMD-LSTM hybrid model, which is an LSTM model combined with ensemble empirical mode decomposition. In this study, ninety percent of the data were adopted to fit the models as a training set, while the subsequent 10% were used to test the prediction effect of the models. The mean absolute percentage error, mean absolute error, and root mean square error were used to evaluate the prediction performances of the models; Results: The results indicated that the number of confirmed cases in California was increasing as of 25 April 2021, with no obvious evidence of a sharp decline. On 25 April 2021, the LSTM model predicted 3666418 confirmed cases, whereas the EEMD-LSTM predicted 3681150. The mean absolute percentage errors for the LSTM and EEMD-LSTM models were 0.0151 and 0.0051, respectively. The mean absolute and root mean square errors were 5.58 × 104 and 5.63 × 104 for the LSTM model and 1.9 × 104 and 2.43 × 104 for the EEMD-LSTM model, respectively; Conclusions: The results showed the advantage of an EEMD-LSTM model over a single LSTM model, and the established EEMD-LSTM model may be suitable for monitoring and evaluating the epidemic situation and providing quantitative analysis evidence for epidemic prevention and control.
Association Analyses of Physical Fitness Parameters and Anxiety Symptoms in Chinese College Students
Authors: Yin Jianjun , Kong Lingfeng , Cui Yufei
Published: December 2022

Poor physical fitness is related to many negative health outcomes, including mental disorders. However, the relationship between physical fitness and anxiety symptoms among college students remains unclear. Therefore, this study investigated whether physical fitness is related to anxiety symptoms in Chinese college students. Cross-sectional data were collected from 6635 men and 4482 women. Physical fitness was measured via a 50-m sprint, a sit-and-reach test, vital capacity, and a standing long jump for both sexes; 1000-m run and pull-up tests for males; and 800-m run and sit-up tests for females. The seven-item Generalized Anxiety Disorder Scale (GAD-7) was used to evaluate anxiety symptoms. Multivariate linear regression showed that better physical fitness was related to lower GAD-7 scores. In addition, multivariate logistic regression analysis showed that better ability in the 50-m sprint, sit-and-reach test, pull-up test, and vital capacity was related with a lower risk of anxiety symptoms in males, and better ability in the 800-m run and standing long jump was related with a lower risk of anxiety symptoms in females. In conclusion, physical fitness was inversely associated with anxiety symptoms in male and female college students. This association was also independent of confounding factors.
Self-Management and Associated Factors among Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study
Authors: Kwon Oh Young , Kim Seung Up , Ahn Sang Hoon , Jang Yeonsoo
Published: December 2022

Self-management is critical and essential for controlling non-alcoholic fatty liver disease, delaying progression, and preventing complications. However, information about the self-management characteristics of this population is scarce. This study explores the characteristics and self-management levels and the factors associated with self-management in patients with non-alcoholic fatty liver disease in Korea. A convenience sample of 150 patients diagnosed with non-alcoholic fatty liver disease was recruited from April to November 2019. Demographics and clinical findings were collected, and self-management, self-efficacy, fatigue, and depressive symptoms were assessed using questionnaires. Multiple linear regression analysis was performed to examine the factors associated with self-management. Self-management levels were moderate (Mean = 3.4, SD = 0.61). Self-management differed significantly by age, sex, marital status, occupation, and health education experience. Self-efficacy (β = 0.074, p = 0.020) showed a significant association with self-management, which explained 25.0% of the variance after controlling for age, sex, marital status, health education experience, occupation, controlled attenuation parameter score, and body mass index. Self-efficacy is a critical determinant of self-management among patients with non-alcoholic fatty liver disease. The study findings could assist healthcare professionals in facilitating self-management compliance and developing multidisciplinary team-based interventions for sustainable self-management.
Next-Generation Sequencing in the Assessment of the Transcriptomic Landscape of DNA Damage Repair Genes in Abdominal Aortic Aneurysm, Chronic Venous Disease and Lower Extremity Artery Disease
Authors: Ruszel Karol P. , Zalewski Daniel P. , Stępniewski Andrzej , Gałkowski Dariusz , Bogucki Jacek , Feldo Marcin , Płachno Bartosz J. , Kocki Janusz , Bogucka-Kocka Anna
Published: December 2022

Vascular diseases are one of the most common causes of death and morbidity. Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD) belong to this group of conditions and exhibit various presentations and courses; thus, there is an urgent need for revealing new biomarkers for monitoring and potential treatment. Next-generation sequencing of mRNA allows rapid and detailed transcriptome analysis, allowing us to pinpoint the most pronounced differences between the mRNA expression profiles of vascular disease patients. Comparison of expression data of 519 DNA-repair-related genes obtained from mRNA next-generation sequencing revealed significant transcriptomic marks characterizing AAA, CVD and LEAD. Statistical, gene set enrichment analysis (GSEA), gene ontology (GO) and literature analyses were applied and highlighted many DNA repair and accompanying processes, such as cohesin functions, oxidative stress, homologous recombination, ubiquitin turnover, chromatin remodelling and DNA double-strand break repair. Surprisingly, obtained data suggest the contribution of genes engaged in the regulatory function of DNA repair as a key component that could be used to distinguish between analyzed conditions. DNA repair–related genes depicted in the presented study as dysregulated in AAA, CVD and LEAD could be utilized in the design of new biomarkers or therapies associated with these diseases.
0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial
Authors: Sosne Gabriel , Kleinman Hynda K. , Springs Clark , Gross Robert Hollis , Sung Jihye , Kang Shinwook
Published: December 2022

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan–Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients.
Agronomic Trait Analysis and Genetic Mapping of a New Wheat Semidwarf Gene Rht-SN33d
Authors: Wang Chaojie , Zhang Lili , Xie Yongdun , Irshad Ahsan , Guo Huijun , Gu Jiayu , Zhao Linshu , Xiong Hongchun , Zhao Shirong , Wang Chengshe , Liu Luxiang
Published: December 2022

Plant height is a key agronomic trait that is closely to the plant morphology and lodging resistance in wheat. However, at present, the few dwarf genes widely used in wheat breeding have narrowed wheat genetic diversity. In this study, we selected a semi-dwarf wheat mutant dwarf33 that exhibits decreased plant height with little serious negative impact on other agronomic traits. Genetic analysis and mutant gene mapping indicated that dwarf33 contains a new recessive semi-dwarf gene Rht-SN33d, which was mapped into ~1.3 Mb interval on the 3DL chromosome. The gibberellin metabolism-related gene TraesCS3D02G542800, which encodes gibberellin 2-beta-dioxygenase, is considered a potential candidate gene of Rht-SN33d. Rht-SN33d reduced plant height by approximately 22.4% in mutant dwarf33. Further study revealed that shorter stem cell length may be the main factor causing plant height decrease. In addition, the coleoptile length of dwarf33 was just 9.3% shorter than that of wild-type Shaannong33. These results will help to expand our understanding of new mechanisms of wheat height regulation, and obtain new germplasm for wheat improvement.
Improvement of Fertilization Capacity and Developmental Ability of Vitrified Bovine Oocytes by JUNO mRNA Microinjection and Cholesterol-Loaded Methyl-β-Cyclodextrin Treatment
Authors: Xu Xi , Hao Tong , Komba Emma , Yang Baigao , Hao Haisheng , Du Weihua , Zhu Huabin , Zhang Hang , Zhao Xueming
Published: December 2022

Vitrification of oocytes is crucial for embryo biotechnologies, germplasm cryopreservation of endangered and excellent female animals, and the fertility of humans. However, vitrification significantly impairs the fertilization ability of oocytes, which significantly limits its widely used application. JUNO protein, a receptor for Izumo1, is involved in sperm-oocyte fusion and is an indispensable protein for mammalian fertilization, and its abundance is susceptible to vitrification. However, it is still unclear how vitrification reduces the fertilization capacity of bovine oocytes by affecting JUNO protein. This study was designed to investigate the effect of vitrification on the abundance and post-translational modifications of JUNO protein in bovine oocytes. Our results showed that vitrification did not alter the amino acid sequence of JUNO protein in bovine oocytes. Furthermore, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis results showed that vitrification significantly reduced the number and changed the location of disulfide bonds, and increased the number of both phosphorylation and glycosylation sites of JUNO protein in bovine oocytes. Finally, the fertilization capacity and development ability of vitrified oocytes treated with 200 pg JUNO mRNA microinjection and cholesterol-loaded methyl-β-cyclodextrin (CLC/MβCD) were similar to those of fresh oocytes. In conclusion, our results showed that vitrification of bovine oocytes did not alter the protein sequence of JUNO, but induced post-translational modifications and changed protein abundance. Moreover, the fertilization and development ability of vitrified bovine oocytes were improved by the combination treatment of JUNO mRNA microinjection and CLC/MβCD.
Phenotypic and Safety Assessment of the Cheese Strain Lactiplantibacillus plantarum LL441, and Sequence Analysis of its Complete Genome and Plasmidome
Authors: Flórez Ana Belén , Vázquez Lucía , Rodríguez Javier , Mayo Baltasar
Published: December 2022

This work describes the phenotypic typing and complete genome analysis of LL441, a dairy Lactiplantibacillus plantarum strain. LL441 utilized a large range of carbohydrates and showed strong activity of some carbohydrate-degrading enzymes. The strain grew slowly in milk and produced acids and ketones along with other volatile compounds. The genome of LL441 included eight circular molecules, the bacterial chromosome, and seven plasmids (pLL441-1 through pLL441-7), ranging in size from 8.7 to 53.3 kbp. Genome analysis revealed vast arrays of genes involved in carbohydrate utilization and flavor formation in milk, as well as genes providing acid and bile resistance. No genes coding for virulence traits or pathogenicity factors were detected. Chromosome and plasmids were packed with insertion sequence (IS) elements. Plasmids were also abundant in genes encoding heavy metal resistance traits and plasmid maintenance functions. Technologically relevant phenotypes linked to plasmids, such as the production of plantaricin C (pLL441-1), lactose utilization (pLL441-2), and bacteriophage resistance (pLL441-4), were also identified. The absence of acquired antibiotic resistance and of phenotypes and genes of concern suggests L. plantarum LL441 be safe. The strain might therefore have a use as a starter or starter component in dairy and other food fermentations or as a probiotic.
Prion Mutations in Republic of Republic of Korea, China, and Japan
Authors: Kim Dan Yeong , Shim Kyu Hwan , Bagyinszky Eva , An Seong Soo A.
Published: December 2022

Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt–Jakob Disease (CJD), Gerstmann–Sträussler–Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.
Supermagnetic Human Serum Albumin (HSA) Nanoparticles and PLGA-Based Doxorubicin Nanoformulation: A Duet for Selective Nanotherapy
Authors: Malinovskaya Julia , Salami Rawan , Valikhov Marat , Vadekhina Veronika , Semyonkin Aleksey , Semkina Alevtina , Abakumov Maxim , Harel Yifat , Levy Esthy , Levin Tzuriel , Persky Rachel , Chekhonin Vladimir , Lellouche Jean-Paul , Melnikov Pavel , Gelperina Svetlana
Published: December 2022

Predicting the ability of nanoparticles (NP) to access the tumor is key to the success of chemotherapy using nanotherapeutics. In the present study, the ability of the dual NP-based theranostic system to accumulate in the tumor was evaluated in vivo using intravital microscopy (IVM) and MRI. The system consisted of model therapeutic doxorubicin-loaded poly(lactide-co-glycolide) NP (Dox-PLGA NP) and novel hybrid Ce3/4+-doped maghemite NP encapsulated within the HSA matrix (hMNP) as a supermagnetic MRI contrasting agent. Both NP types had similar sizes of ~100 nm and negative surface potentials. The level of the hMNP and PLGA NP co-distribution in the same regions of interest (ROI, ~2500 µm2) was assessed by IVM in mice bearing the 4T1-mScarlet murine mammary carcinoma at different intervals between the NP injections. In all cases, both NP types penetrated into the same tumoral/peritumoral regions by neutrophil-assisted extravasation through vascular micro- and macroleakages. The maximum tumor contrasting in MRI scans was obtained 5 h after hMNP injection/1 h after PLGA NP injection; the co-distribution level at this time reached 78%. Together with high contrasting properties of the hMNP, these data indicate that the hMNP and PLGA NPs are suitable theranostic companions. Thus, analysis of the co-distribution level appears to be a useful tool for evaluation of the dual nanoparticle theranostics, whereas assessment of the leakage areas helps to reveal the tumors potentially responsive to nanotherapeutics.
Preparation of Hydrogels Based on Modified Pectins by Tuning Their Properties for Anti-Glioma Therapy
Authors: Belousov Andrei , Patlay Aleksandra , Silant’ev Vladimir , Kovalev Valeri V. , Kumeiko Vadim
Published: December 2022

The extracellular matrix (ECM) of the central nervous system (CNS), characterized by low stiffness and predominance of carbohydrates on protein components, mediates limited cell proliferation and migration. Pectins are polysaccharides derived from plants and could be very promising for a tunable hydrogel design that mimics the neural ECM. Aiming to regulate gel structure and viscoelastic properties, we elaborated 10 variants of pectin-based hydrogels via tuning the concentration of the polymer and the number of free carboxyl groups expressed in the degree of esterification (DE). Viscoelastic properties of hydrogels varied in the range of 3 to 900 Pa for G′ and were chosen as the first criteria for the selection of variants suitable for CNS remodeling. For extended reciprocal characterization, two pairs of hydrogels were taken to test pectins with opposite DEs close to 0% and 50%, respectively, but with a similar rheology exceeding 100 Pa (G′), which was achieved by adjusting the concentration of pectin. Hydrogel swelling properties and in vitro stability, together with structure characterization using SEM and FTIR spectroscopy, displayed some differences that may sense for biomedical application. Bioassays on C6 and U87MG glioblastoma cultures testified the potential prospects of the anti-glioma activity of hydrogels developed by decreasing cell proliferation and modulating migration but supporting the high viability of neural cells.
Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool
Authors: Kalinkova Lenka , Sevcikova Aneta , Stevurkova Viola , Fridrichova Ivana , Ciernikova Sona
Published: December 2022

DNA methylation represents a crucial mechanism of epigenetic regulation in hematologic malignancies. The methylation process is controlled by specific DNA methyl transferases and other regulators, which are often affected by genetic alterations. Global hypomethylation and hypermethylation of tumor suppressor genes are associated with hematologic cancer development and progression. Several epi-drugs have been successfully implicated in the treatment of hematologic malignancies, including the hypomethylating agents (HMAs) decitabine and azacytidine. However, combinations with other treatment modalities and the discovery of new molecules are still the subject of research to increase sensitivity to anti-cancer therapies and improve patient outcomes. In this review, we summarized the main functions of DNA methylation regulators and genetic events leading to changes in methylation landscapes. We provide current knowledge about target genes with aberrant methylation levels in leukemias, myelodysplastic syndromes, and malignant lymphomas. Moreover, we provide an overview of the clinical trials, focused mainly on the combined therapy of HMAs with other treatments and its impact on adverse events, treatment efficacy, and survival rates among hematologic cancer patients. In the era of precision medicine, a transition from genes to their regulation opens up the possibility of an epigenetic-based approach as a diagnostic, prognostic, and therapeutic tool.
Toward Quantitative Models in Safety Assessment: A Case Study to Show Impact of Dose–Response Inference on hERG Inhibition Models
Authors: Melnikov Fjodor , Anger Lennart T. , Hasselgren Catrin
Published: December 2022

Due to challenges with historical data and the diversity of assay formats, in silico models for safety-related endpoints are often based on discretized data instead of the data on a natural continuous scale. Models for discretized endpoints have limitations in usage and interpretation that can impact compound design. Here, we present a consistent data inference approach, exemplified on two data sets of Ether-à-go-go-Related Gene (hERG) K+ inhibition data, for dose–response and screening experiments that are generally applicable for in vitro assays. hERG inhibition has been associated with severe cardiac effects and is one of the more prominent safety targets assessed in drug development, using a wide array of in vitro and in silico screening methods. In this study, the IC50 for hERG inhibition is estimated from diverse historical proprietary data. The IC50 derived from a two-point proprietary screening data set demonstrated high correlation (R = 0.98, MAE = 0.08) with IC50s derived from six-point dose–response curves. Similar IC50 estimation accuracy was obtained on a public thallium flux assay data set (R = 0.90, MAE = 0.2). The IC50 data were used to develop a robust quantitative model. The model’s MAE (0.47) and R2 (0.46) were on par with literature statistics and approached assay reproducibility. Using a continuous model has high value for pharmaceutical projects, as it enables rank ordering of compounds and evaluation of compounds against project-specific inhibition thresholds. This data inference approach can be widely applicable to assays with quantitative readouts and has the potential to impact experimental design and improve model performance, interpretation, and acceptance across many standard safety endpoints.
Effect of Quercetin on mitoBKCa Channel and Mitochondrial Function in Human Bronchial Epithelial Cells Exposed to Particulate Matter
Authors: Dabrowska Adrianna , Zajac Miroslaw , Bednarczyk Piotr , Lukasiak Agnieszka
Published: December 2022

Particulate matter (PM) exposure increases reactive oxygen species (ROS) levels. It can lead to inflammatory responses and damage of the mitochondria thus inducing cell death. Recently, it has been shown that potassium channels (mitoK) located in the inner mitochondrial membrane are involved in cytoprotection, and one of the mechanisms involves ROS. To verify the cytoprotective role of mitoBKCa, we performed a series of experiments using a patch-clamp, transepithelial electrical resistance assessment (TEER), mitochondrial respiration measurements, fluorescence methods for the ROS level and mitochondrial membrane potential assessment, and cell viability measurements. In the human bronchial epithelial cell model (16HBE14σ), PM < 4 μm in diameter (SRM-PM4.0) was used. We observed that PM decreased TEER of HBE cell monolayers. The effect was partially abolished by quercetin, a mitoBKCa opener. Consequently, quercetin decreased the mitochondrial membrane potential and increased mitochondrial respiration. The reduction of PM-induced ROS level occurs both on cellular and mitochondrial level. Additionally, quercetin restores HBE cell viability after PM administration. The incubation of cells with PM substantially reduced the mitochondrial function. Isorhamnetin had no effect on TEER, the mitoBKCa activity, respiratory rate, or mitochondrial membrane potential. Obtained results indicate that PM has an adverse effect on HBE cells at the cellular and mitochondrial level. Quercetin is able to limit the deleterious effect of PM on barrier function of airway epithelial cells. We show that the effect in HBE cells involves mitoBKCa channel-activation. However, quercetin’s mechanism of action is not exclusively determined by modulation of the channel activity.
The Role of Staphylococcus aureus and Its Toxins in the Pathogenesis of Allergic Asthma
Authors: Jorde Ilka , Schreiber Jens , Stegemann-Koniszewski Sabine
Published: December 2022

Bronchial asthma is one of the most common chronic diseases worldwide and affects more than 300 million patients. Allergic asthma affects the majority of asthmatic children as well as approximately 50% of adult asthmatics. It is characterized by a Th2-mediated immune response against aeroallergens. Many aspects of the overall pathophysiology are known, while the underlying mechanisms and predisposing factors remain largely elusive today. Over the last decade, respiratory colonization with Staphylococcus aureus (S. aureus), a Gram-positive facultative bacterial pathogen, came into focus as a risk factor for the development of atopic respiratory diseases. More than 30% of the world’s population is constantly colonized with S. aureus in their nasopharynx. This colonization is mostly asymptomatic, but in immunocompromised patients, it can lead to serious complications including pneumonia, sepsis, or even death. S. aureus is known for its ability to produce a wide range of proteins including toxins, serine-protease-like proteins, and protein A. In this review, we provide an overview of the current knowledge about the pathophysiology of allergic asthma and to what extent it can be affected by different toxins produced by S. aureus. Intensifying this knowledge might lead to new preventive strategies for atopic respiratory diseases.
Tuning of the Titanium Oxide Surface to Control Magnetic Properties of Thin Iron Films
Authors: Chojenka Juliusz , Zarzycki Arkadiusz , Perzanowski Marcin , Krupiński Michał , Fodor Tamás , Vad Kálmán , Marszałek Marta
Published: December 2022

We describe the magnetic properties of thin iron films deposited on the nanoporous titanium oxide templates and analyze their dependance on nanopore radius. We then compare the results to a continuous iron film of the same thickness. Additionally, we investigate the evolution of the magnetic properties of these films after annealing. We demonstrate that the M(H) loops consist of two magnetic phases originating from the iron layer and iron oxides formed at the titanium oxide/iron interface. We perform deconvolution of hysteresis loops to extract information for each magnetic phase. Finally, we investigate the magnetic interactions between the phases and verify the presence of exchange coupling between them. We observe the altering of the magnetic properties by the nanopores as a magnetic hardening of the magnetic material. The ZFC-FC (Zero-field cooled/field cooled) measurements indicate the presence of a disordered glass state below 50 K, which can be explained by the formation of iron oxide at the titanium oxide-iron interface with a short-range magnetic order.
Comparative Analysis of the Wear of NC11LV and Hardox 600 Steel Used in Tools for Extrusion of Clay Strands in the Process of Producing Ceramic Roof Tiles
Authors: Hawryluk Marek , Lachowicz Marzena M. , Marzec Jan , Nowak Kamila , Suliga Maciej
Published: December 2022

This article presents the results of a comparative analysis performed with respect to the wear of tools used for the extrusion of a clay strand (for ceramic roof tile) made from two materials: steel NC11LV and steel Hardox 600. The aim of the studies was to determine the causes and mechanisms of wear as well as to evaluate the possibility of choosing the optimal material, mostly in respect to its resistance to intensive wear as well as an increase in the operation time. The results of the conducted investigations included: an analysis of the technology, thermovision measurements of the forming process, a macroscopic analysis combined with 3D scanning of the worn tools, ball-on-disc tests of the sliding wear resistance and hardness measurements. The obtained results demonstrated that the tools made of steel NC11LV were much less worn than those made of steel Hardox 600, as the operation time for the NC11LV steel tools was almost three times longer. The results of the ball-on-disc tests showed a similar manner of wear for both materials (with the working temperature of about 50 °C). The higher durability of the tools made from steel NC11LV can be an effect of a slightly lower coefficient of friction in the initial period of operation as well as the presence of hard carbides, which means increased hardness and thus also higher wear resistance at working temperatures.
The Composites of PCL and Tetranuclear Titanium(IV)–Oxo Complex with Acetylsalicylate Ligands—Assessment of Their Biocompatibility and Antimicrobial Activity with the Correlation to EPR Spectroscopy
Authors: Śmigiel Julia , Piszczek Piotr , Wrzeszcz Grzegorz , Jędrzejewski Tomasz , Golińska Patrycja , Radtke Aleksandra
Published: December 2022

In our research, we have focused on the biological studies on composite materials produced by the dispersion of titanium(IV)–oxo complex (TOC) with acetylsalicylate ligands in a poly(ε-caprolactone) (PCL) matrix, which is a biodegradable thermoplastic polymer increasingly used in the production of medical devices. Using PCL as a matrix for the biologically active compounds, such as antimicrobial agents, antibiotics or other active medical substances, from which these individuals can be gradually released is fully understable. Composites of PCL + nTOC (n = 10, 15 and 20 wt.%) have been produced and, in such a form, the biological properties of TOCs have been estimated. Direct and indirect cytotoxicity studies have been performed in vitro on L929 and human umbilical vein endothelial cells (HUVEC) cell lines. The antibacterial and antifungal activity of the PCL + TOC samples have been assessed against two Staphylococcus aureus (ATCC 6538 and ATCC 25923) reference strains, two Escherichia coli (ATCC 8739 and ATCC 25922) reference strains and yeast of Candida albicans ATCC 10231. Obtained results have been correlated with electron paramagnetic resonance (EPR) spectroscopy data. We could conclude that photoexcitation by visible light of the surface of PCL + nTOC composite foils lead to the formation of different paramagnetic species, mainly O−, which slowly disappears over time; however, their destructive effect on bacteria and cells has been proven.
Oxidation of Cyclohexane/Cyclohexanone Mixture with Oxygen as Alternative Method of Adipic Acid Synthesis
Authors: Lisicki Dawid , Orlińska Beata , Marek Adam A. , Bińczak Jakub , Dziuba Krzysztof , Martyniuk Tomasz
Published: December 2022

Herein, an alternative method for adipic acid (AA) synthesis of industrial importance has been reported. The proposed novel method involves the one-step, solvent-free oxidation of a cyclohexane/cyclohexanone (CH/CH=O) mixture, with a cheap oxidizing agent such as O2 or air under mild conditions in the presence of N-hydroxyphtalimide (NHPI) and transition metals as catalysts. It has been showed that CH/CH=O mixture under applied mild conditions oxidized faster than CH and CH=O separately. This was due to the greater oxidizability of CH=O compared to CH. The peroxyl radicals formed by CH=O oxidation initiated the oxidation of the less reactive CH. Additionally, CH=O increased the polarity of the reaction mixture, promoting the solubility of NHPI. The influence of type and amount of catalyst, cyclohexane to cyclohexanone ratio, temperature, time, type of oxidizing agent on the composition of CH/CH=O oxidation products have been reported.
Ternary Copper Tungsten Sulfide (Cu2WS4) Nanoparticles Obtained through a Solvothermal Approach: A Bi-Functional Electrocatalyst for the Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER)
Authors: Muddassir Mohd. , Alarifi Abdullah , Abduh Naaser A. Y. , Saeed Waseem Sharaf , Karami Abdulnasser Mahmoud , Afzal Mohd
Published: December 2022

In this work, Cu2WS4 nanoparticles have been synthesized via a solvothermal decomposition approach using a heterobimetallic single source precursor, WCu2S4(PPh3)3. The single source precursor, WCu2S4(PPh3)3, has been characterized using multinuclear NMR spectroscopy, while Cu2WS4 nanoparticles have been characterized by powder X-ray diffraction (PXRD) for which Rietveld refinement has been performed to authenticate the lattice structure of the decomposed product, Cu2WS4. Furthermore, FESEM and EDAX analyses have been performed to assess the morphology and composition of Cu2WS4. An electrochemical study in acidic as well as basic media suggested that Cu2WS4 nanoparticles possess efficient bifunctional activity towards electrochemical hydrogen as well as oxygen evolution reactions. Linear sweep voltammetry (LSV) performed in 0.5 N H2SO4 indicates an onset potential for the HER of 462 mV and a Tafel slope of 140 mV dec−1. While LSV performed in 0.1 M KOH indicates an onset potential for the OER of 190 mV and a Tafel Slope of 117 mV dec−1.
The Effect of Cementitious Materials on the Engineering Properties and Pore Structure of Concrete with Recycled Fine Aggregate
Authors: Liu Zihao , Takasu Koji , Suyama Hiroki , Koyamada Hidehiro , Liu Shilun , Hao Qi
Published: December 2022

With the rapid development of urbanization, the construction industry consumes a lot of cement and produces a large amount of construction waste. To overcome this situation, the rational use of recycled aggregate produced from waste concrete is one of solutions. In some countries, the building industry has approved the use of recycled coarse aggregates in concrete, with some limits. However, practically all existing standards and regulations prohibit the use of recycled fine aggregate (RFA) in concrete. Therefore, study on improving the performance of RFA concrete is vital. In this study, the effects of fly ash and GGBS on concrete with RFA were investigated. Compressive strength, pore structure, drying shrinkage and accelerated carbonation were tested. The correlation between the pore structure and properties of concrete was analyzed. The results show that adding fly ash and GGBS to RFA concrete increased its compressive strength, modified pore structure, reduced drying shrinkage, and even achieved higher compressive strength and lower drying shrinkage than normal concrete. The compressive strength was mainly affected by the capillary pores, and the carbonation was mainly affected by the gel pores.
Computer Alloy Design of Ti Modified Al-Si-Mg-Sr Casting Alloys for Achieving Simultaneous Enhancement in Strength and Ductility
Authors: Zhang Shaoji , Yi Wang , Zhong Jing , Gao Jianbao , Lu Zhao , Zhang Lijun
Published: December 2022

In this paper, an efficient design of a Ti-modified Al-Si-Mg-Sr casting alloy with simultaneously enhanced strength and ductility was achieved by integrating computational thermodynamics, machine learning, and key experiments within the Bayesian optimization framework. Firstly, a self-consistent Al-Si-Mg-Sr-Ti quinary thermodynamic database was established by the calculation of phase diagram method and verified by key experiments. Based on the established thermodynamic database, a high-throughput Scheil-Gulliver solidification simulation of the A356-0.005Sr alloy with different Ti contents was carried out to establish the “composition-microstructure” quantitative relationship of the alloy. Then, by combining the computational thermodynamic, machine learning, and experimental data within the Bayesian optimization framework, the relationship “composition/processing-microstructure-properties” of A356-0.005Sr with different Ti contents was constructed and validated by the key experiments. Furthermore, the optimum alloy composition of the Ti-modified A356-0.005Sr casting alloy was designed based on this integration method with the Bayesian optimization framework and verified by the experiments. It is anticipated that the present integration method may serve as a general one for the efficient design of casting alloys, especially in the high-dimensional composition space.