bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Soil Heavy Metal Pollution and Health Risks in Different Functional Areas on the Northern Slope of the Eastern Tianshan Mountains in Xinjiang, NW China
Authors: Asaiduli Halidan , Abliz Abdugheni , Abulizi Abudukeyimu , Sun Xiaoli , Ye Panqing
Published: March 2023

In typical semi-arid areas, the timely and effective monitoring and evaluation of soil heavy metal pollution are of critical importance to prevent soil deterioration and achieve the sustainable use of soil resources. To further understand the degree of soil heavy metal pollution in different functional areas, we studied the soil heavy metal pollution on the northern slope of the eastern Tianshan Mountains in Xinjiang. We collected 104 surface soil samples from typical commercial (A), industrial (B), and agricultural (C) areas with different land-use patterns. The contents of Zn, Cu, Cr, Pb, As, and Hg in the soil of different functional areas were evaluated using the geo-accumulation index, the single-factor pollution index, and potential ecological risk. The results showed that the contents of Pb, As, and Hg in soils of different functional areas exceeded 4.47, 8.03, and 1.5 times the background values of Xinjiang soil, respectively. The average contents of Zn, Cu, and Cr were lower than the background values of Xinjiang soil. Except for As in different functional areas, the contents of the other elements in the different functional areas reached the level of soil environmental quality standards in China (GB15618-2018). The geo-accumulation index of heavy metals in different functional areas was in the order of Area C > Area A > Area B, indicating that Area C was the most polluted. The results of the single-factor pollution index showed that the pollution levels of Pb, As, and Hg were higher, and the pollution levels of Cr, Cu, and Zn were lower. The results of the potential ecological risk index showed that the northwest of Area A was higher, the southeast of Area B was more polluted, and the central and eastern parts of Area C were more polluted. From the perspective of spatial distribution, the spatial distribution characteristics of Zn and Cr elements in different functional areas are consistent, but the spatial distribution characteristics of Cu, Pb, As, and Hg in different functional areas are quite different. The high values of these four elements are mainly distributed in residential areas, factories, and metal smelters. It is necessary to divide the functional areas based on different land-use patterns, and the prevention of soil single-element and heavy metal pollution in different functional areas is reasonable for land resources and provides a scientific basis for the effective planning of quality assurance.
Evaluation of Size of Trunk Asymmetry in Children Practicing Selected Sports Disciplines
Authors: Twarowska-Grybalow Natalia , Truszczyńska-Baszak Aleksandra
Published: March 2023

(1) Background: The aim of the study was to assess the body posture of children practicing selected sports disciplines and to compare it to the body posture of non-training children. (2) Methods: 247 children practicing a selected discipline either in primary sports schools or in sports clubs constituted the study group. The control group was composed of 63 children that did not practice any sport. The study of body posture by using the Moiré method allowed for assessing the size of parameters determining body posture. Selected parameters characterizing the position of the shoulders and shoulder blades, the waist triangle, and the position of the posterior iliac spines were analyzed. (3) Results: The differences in the selected parameters were not statistically significant in all parameters except the model describing the values determining the depth of the shoulder blades that were measured in millimeters between the groups. (4) Conclusions: Most of the examined people had correct body posture in the sagittal plane, regardless of the type of sport practiced. In all the examined groups, the most common dysfunctions were asymmetries of moderate intensity in the frontal plane. The results of our own research did not allow us to clearly state whether practicing different sports disciplines and different training loads has a negative or positive impact on body posture. The lack of asymmetry of high intensity in the groups of people practicing various sports disciplines, despite the fact that the given disciplines are asymmetric, may indicate that exercises during the training process are correctly selected.
Anxious, Depressed, and Suicidal: Crisis Narratives in University Student Mental Health and the Need for a Balanced Approach to Student Wellness
Authors: Bantjes Jason , Hunt Xanthe , Stein Dan J.
Published: March 2023

There is growing global awareness of the poor mental health of university students, as well as the need to improve students’ access to services and expand the range of available evidence-based interventions. However, a crisis narrative is emerging, particularly in the wake of the COVID-19 pandemic, that runs the risk of positioning all students as potential patients in need of formal psychiatric interventions. Our aim in this commentary is to critically present the evidence that supports increased attention to student mental health, while also raising a concern that the crisis narrative may itself have unintended harmful consequences. We highlight some of the potential dangers of overtly medicalizing and thus pathologizing students’ experiences of everyday distress, inadequacies of formal diagnostic categories, limitations of focusing narrowly on psychotherapeutic and psychiatric interventions, and the short-sightedness of downplaying key social determinants of students’ distress. We argue for an integrative and balanced public health approach that draws on the rigor of psychiatric epidemiology and the advances that have been made to identify evidence-based interventions for students, while simultaneously being mindful of the shortcomings and potential dangers of working narrowly within the paradigm of diagnostic labels and psychotherapeutic interventions.
Prevalence of Burnout among Teachers during the COVID-19 Pandemic: A Meta-Analysis
Authors: Ozamiz-Etxebarria Naiara , Legorburu Fernnadez Idoia , Lipnicki Darren M. , Idoiaga Mondragon Nahia , Santabárbara Javier
Published: March 2023

Since the start of the COVID-19 pandemic, many studies have found that there has been a lot of teacher overload. One of the additional burdens has been that they have had to teach online. In addition, when they returned to face-to-face classes, they had to follow all the hygiene rules so that the COVID-19 virus would not spread. It is therefore not surprising that, during this pandemic period, high levels of psychological symptoms have been reported among teachers. Among this symptomatology, burnout has been very frequent among teachers. Therefore, the aim of this study is to conduct a meta-analysis to determine the overall prevalence of burnout among teachers during the COVID-19 pandemic. For this purpose, a search was conducted for cross-sectional studies listed in PubMed from 1 December 2019 to 14 February 2022 that reported on the prevalence of burnout among teachers. A total of nine studies from eight different countries in Africa, Asia, Europe, and North and South America, were included in this study. The pooled prevalence of burnout among teachers was 52% (95% CI 33–71%), which is higher than burnout rates reported for health professionals. There was significant heterogeneity between studies (I2 = 99%, p-value < 0.001), and the prevalence of burnout was higher in women and school teachers (compared to university educators), and lower in American studies. This meta-analysis concludes that teachers worldwide experienced a high rate of burnout during the COVID-19 pandemic. This has implications not only for the teachers themselves, but also for the quality of the education they were able to provide. This education has an influence on the student population. The possible long-term effects are yet to be determined.
Applying Machine Learning to Construct a Model of Risk of Depression in Patients Following Cardiac Surgery with the Use of the SF-12 Survey
Authors: Nowicka-Sauer Katarzyna , Jarmoszewicz Krzysztof , Molisz Andrzej , Sobczak Krzysztof , Sauer Marta , Topolski Mariusz
Published: March 2023

Background: Depression is a common problem in patients with cardiovascular diseases. Identifying a risk factor model of depression has been postulated. A model of the risk of depression would provide a better understanding of this disorder in this population. We sought to construct a model of the risk factors of depression in patients following cardiac surgery, with the use of machine learning. Methods and Measures: Two hundred and seventeen patients (65.4% men; mean age 65.14 years) were asked to complete the short form health survey-12 (SF-12v.2), three months after hospital discharge. Those at risk of depression were identified based on the SF-12 mental component summary (MCS). Centroid class principal component analysis (CCPCA) and the classification and regression tree (CART) were used to design a model. Results: A risk of depression was identified in 29.03% of patients. The following variables explained 82.53% of the variance in depression risk: vitality, limitation of activities due to emotional problems (role-emotional, RE), New York Heart Association (NYHA) class, and heart failure. Additionally, CART revealed that decreased vitality increased the risk of depression to 45.44% and an RE score > 68.75 increased it to 63.11%. In the group with an RE score < 68.75, the NYHA class increased the risk to 41.85%, and heart failure further increased it to 44.75%. Conclusion: Assessing fatigue and vitality can help health professionals with identifying patients at risk of depression. In addition, assessing functional status and dimensions of fatigue, as well as the impact of emotional state on daily functioning, can help determine effective intervention options.
Adherence to Pre-Exposure Prophylaxis (PrEP) among Men Who Have Sex with Men (MSM) in Portuguese-Speaking Countries
Authors: Sousa Alvaro Francisco Lopes de , Lima Shirley Veronica Melo Almeida , Ribeiro Caíque Jordan Nunes , de Sousa Anderson Reis , Barreto Nilo Manoel Pereira Vieira , Camargo Emerson Lucas Silva , Araújo Agostinho Antônio Cruz , dos Santos Allan Dantas , Bezerra-Santos Márcio , Fortunato Mariana dos Reis , Possani Matheus Arantes , Santos Adriano José dos , Lima João Lucas Tavares de , Gir Elucir , Fronteira Inês , Mendes Isabel Amélia Costa
Published: March 2023

Strengthening strategies to improve adherence to the use of pre-exposure prophylaxis (PrEP) in key populations constitutes a global health priority to be achieved across countries, especially in countries that share a high flow of people such as Brazil and Portugal. This study aimed to analyze the factors associated with adherence to PrEP among MSM from two Portuguese-speaking countries, highlighting the opportunities and preventive strategies for the global health scenario. This was a cross-sectional analytical online survey conducted from January 2020 to May 2021 with MSM in Brazil and Portugal. For analysis of the data, the Poisson regression model was used to estimate the prevalence ratio (PR) for developing a model to evaluate the associated factors in both countries in a comparative and isolated way. Adherence to PrEP use corresponded to 19.5% (n = 1682) of the overall sample: 18.3% (n = 970) for Brazil and 21.5% (n = 712) for Portugal. Having more than two sex partners in the last 30 days (aPR: 30.87) and routinely undergoing HIV tests (aPR: 26.21) increased the use of this medication. Being an immigrant (PR: 1.36) and knowing the partner’s serological status (PR: 1.28) increased adherence to PrEP in Portugal, whereas, in Brazil, it was being an immigrant (PR: 0.83) and not knowing the serological status (PR: 2.24) that promoted the use of this medication. Our findings reinforce the need to invest in programs and strategies to improve access and adherence to PrEP, especially in key populations.
Cross-Sectional Study of Location-Based Built Environments, Physical Activity, Dietary Intake, and Body Mass Index in Adult Twins
Authors: Duncan Glen E. , Sun Feiyang , Avery Ally R. , Hurvitz Philip M. , Moudon Anne Vernez , Tsang Siny , Williams Bethany D.
Published: March 2023

We examined relationships between walkability and health behaviors between and within identical twin pairs, considering both home (neighborhood) walkability and each twin’s measured activity space. Continuous activity and location data (via accelerometry and GPS) were obtained in 79 pairs over 2 weeks. Walkability was estimated using Walk Score® (WS); home WS refers to neighborhood walkability, and GPS WS refers to the mean of individual WSs matched to every GPS point collected by each participant. GPS WS was assessed within (WHN) and out of the neighborhood (OHN), using 1-mile Euclidean (air1mi) and network (net1mi) buffers. Outcomes included walking and moderate-to-vigorous physical activity (MVPA) bouts, dietary energy density (DED), and BMI. Home WS was associated with WHN GPS WS (b = 0.71, SE = 0.03, p < 0.001 for air1mi; b = 0.79, SE = 0.03, p < 0.001 for net1mi), and OHN GPS WS (b = 0.18, SE = 0.04, p < 0.001 for air1mi; b = 0.22, SE = 0.04, p < 0.001 for net1mi). Quasi-causal relationships (within-twin) were observed for home and GPS WS with walking (ps < 0.01), but not MVPA, DED, or BMI. Results support previous literature that neighborhood walkability has a positive influence on walking.
Role of Klotho and AGE/RAGE-Wnt/β-Catenin Signalling Pathway on the Development of Cardiac and Renal Fibrosis in Diabetes
Authors: Martín-Carro Beatriz , Martín-Vírgala Julia , Fernández-Villabrille Sara , Fernández-Fernández Alejandra , Pérez-Basterrechea Marcos , Navarro-González Juan F. , Donate-Correa Javier , Mora-Fernández Carmen , Dusso Adriana S. , Carrillo-López Natalia , Panizo Sara , Naves-Díaz Manuel , Fernández-Martín José L. , Cannata-Andía Jorge B. , Alonso-Montes Cristina
Published: March 2023

Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, markers of fibrosis (collagen deposition, fibronectin, TGF-β1, and Wnt/β-catenin pathway), hypertrophy of the kidney and/or heart were analysed. At the end of study, diabetic rats showed higher levels of urinary sKlotho, AGEs and sRAGE and lower serum sKlotho compared with controls without differences in the renal Klotho expression. A significant positive correlation was found between urinary sKlotho and AGEs and urinary albumin/creatinine ratio (uACR). Fibrosis and RAGE levels were significantly higher in the heart without differences in the kidney of diabetic rats compared to controls. The results also suggest the increase in sKlotho and sRAGE excretion may be due to polyuria in the diabetic rats.
Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis
Authors: Geronikaki Athina , Eleutheriou Phaedra T.
Published: March 2023

This is the first part of a Special Issue on enzymes and enzymes inhibitors and their applications in medicine and diagnosis [...]
Antitumor Effect of Iscador on Breast Cancer Cell Lines with Different Metastatic Potential
Authors: Robev Bozhil , Iliev Ivan , Tsoneva Iana , Momchilova Albena , Nesheva Alexandrina , Kostadinova Aneliya , Staneva Galya , Nikolova Biliana
Published: March 2023

Studies were performed for the first time on the effect of Iscador Qu and Iscador M on phototoxicity, cytotoxicity, antiproliferative activity, changes in ξ-potential of cells, membrane lipid order, actin cytoskeleton organization and migration on three breast cancer lines with different metastatic potential: MCF10A (control), MCF-7 (low metastatic) and MDA-MB231 (high metastatic) cells. The tested Iscador Qu and M did not show any phototoxicity. The antiproliferative effect of Iscador species appeared to be dose-dependent and was related to the metastatic potential of the tested cell lines. A higher selectivity index was obtained for Iscador Qu and M towards the low metastatic MCF-7 cell line compared to the high metastatic MDA-MB-231. Iscador Qu demonstrated higher selectivity for both cancer cell lines compared to Iscador M. The malignant cell lines exhibited a decrease in fibril number and thickness regardless of the type of Iscador used. The strongest effect on migration potential was observed for the low metastatic cancer cell line MCF-7 after Iscador treatment. Both Iscador species induced a slight increase in the percentage of cells in early apoptosis for the low and high metastatic cell lines, MCF-7 and MDA-MB-231, unlike control cells. Changes in the zeta potential and membrane lipid order were observed for the low metastatic MCF-7 cell line in contrast to the high metastatic MDA-MB-231 cells. The presented results reveal a higher potential of Iscador as an antitumor agent for the low metastatic cancer cell line MCF-7 compared to the high metastatic one. Iscador Qu appears to be more potent compared to Iscador M, but at this point, the exact mechanism of action is still unclear and needs further investigations.
Inhibitory Effects of Extracellular Vesicles from iPS-Cell-Derived Mesenchymal Stem Cells on the Onset of Sialadenitis in Sjögren’s Syndrome Are Mediated by Immunomodulatory Splenocytes and Improved by Inhibiting miR-125b
Authors: Zhao Qingguo , Bae Eun-Hye , Zhang Yu , Shahsavari Arash , Lotey Pranayvir , Lee Ryang Hwa , Liu Fei
Published: March 2023

Extracellular vesicles (EVs) from allogeneic-tissue-derived mesenchymal stem cells (MSCs) are promising to improve Sjögren’s syndrome (SS) treatment, but their application is hindered by high variations in and limited expandability of tissue MSCs. We derived standardized and scalable MSCs from iPS cells (iMSCs) and reported that EVs from young but not aging iMSCs (iEVs) inhibited sialadenitis onset in SS mouse models. Here, we aim to determine cellular mechanisms and optimization approaches of SS-inhibitory effects of iEVs. In NOD.B10.H2b mice at the pre-disease stage of SS, we examined the biodistribution and recipient cells of iEVs with imaging, flow cytometry, and qRT-PCR. Intravenously infused iEVs accumulated in the spleen but not salivary glands or cervical lymph nodes and were mainly taken up by macrophages. In the spleen, young but not aging iEVs increased M2 macrophages, decreased Th17 cells, and changed expression of related immunomodulatory molecules. Loading miR-125b inhibitors into aging iEVs significantly improved their effects on repressing sialadenitis onset and regulating immunomodulatory splenocytes. These data indicated that young but not aging iEVs suppress SS onset by regulating immunomodulatory splenocytes, and inhibiting miR-125b in aging iEVs restores such effects, which is promising to maximize production of effective iEVs from highly expanded iMSCs for future clinical application.
Bone and Cartilage Biology
Authors: Nishimura Riko
Published: March 2023

Recent technical and conceptual advances in molecular and cellular biology have dramatically advanced bone and cartilage biology [...]
DNA Methylation of the Dopamine Transporter DAT1 Gene—Bliss Seekers in the Light of Epigenetics
Authors: Chmielowiec Krzysztof , Chmielowiec Jolanta , Masiak Jolanta , Strońska-Pluta Aleksandra , Lachowicz Milena , Boroń Agnieszka , Larysz Dariusz , Dzitkowska-Zabielska Magdalena , Cięszczyk Paweł , Grzywacz Anna
Published: March 2023

DNA methylation (leading to gene silencing) is one of the best-studied epigenetic mechanisms. It is also essential in regulating the dynamics of dopamine release in the synaptic cleft. This regulation relates to the expression of the dopamine transporter gene (DAT1). We examined 137 people addicted to nicotine, 274 addicted subjects, 105 sports subjects and 290 people from the control group. After applying the Bonferroni correction, our results show that as many as 24 out of 33 examined CpG islands had statistically significantly higher methylation in the nicotine-dependent subjects and athletes groups compared to the control group. Analysis of total DAT1 methylation revealed a statistically significant increase in the number of total methylated CpG islands in addicted subjects (40.94%), nicotine-dependent subjects (62.84%) and sports subjects (65.71%) compared to controls (42.36%). The analysis of the methylation status of individual CpG sites revealed a new direction of research on the biological aspects of regulating dopamine release in people addicted to nicotine, people practicing sports and people addicted to psychoactive substances.
Dynamic Association of ESCRT-II Proteins with ESCRT-I and ESCRT-III Complexes during Phagocytosis of Entamoeba histolytica
Authors: Díaz-Hernández Mitzi , Javier-Reyna Rosario , Martínez-Valencia Diana , Montaño Sarita , Orozco Esther
Published: March 2023

By their active movement and voraux phagocytosis, the trophozoites of Entamoeba histolytica constitute an excellent system to investigate the dynamics of the Endosomal Sorting Complex Required for Transport (ESCRT) protein interactions through phagocytosis. Here, we studied the proteins forming the E. histolytica ESCRT-II complex and their relationship with other phagocytosis-involved molecules. Bioinformatics analysis predicted that EhVps22, EhVps25, and EhVps36 are E. histolytica bona fide orthologues of the ESCRT-II protein families. Recombinant proteins and specific antibodies revealed that ESCRT-II proteins interact with each other, with other ESCRT proteins, and phagocytosis-involved molecules, such as the adhesin (EhADH). Laser confocal microscopy, pull-down assays, and mass spectrometry analysis disclosed that during phagocytosis, ESCRT-II accompanies the red blood cells (RBCs) from their attachment to the trophozoites until their arrival to multivesicular bodies (MVBs), changing their interactive patterns according to the time and place of the process. Knocked-down trophozoites in the Ehvps25 gene presented a 50% lower rate of phagocytosis than the controls and lower efficiency to adhere RBCs. In conclusion, ESCRT-II interacts with other molecules during prey contact and conduction throughout the phagocytic channel and trophozoites membranous system. ESCRT-II proteins are members of the protein chain during vesicle trafficking and are fundamental for the continuity and efficiency of phagocytosis.
Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges
Authors: Fan Hueng-Chuen , Chiang Kuo-Liang , Chang Kuang-Hsi , Chen Chuan-Mu , Tsai Jeng-Dau
Published: March 2023

Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child’s developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients’ clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.
Exploring the Non-Covalent Bonding in Water Clusters
Authors: Seijas Luis E. , Zambrano Cesar H. , Almeida Rafael , Alí-Torres Jorge , Rincón Luis , Torres Fernando Javier
Published: March 2023

QTAIM and source function analysis were used to explore the non-covalent bonding in twelve different water clusters (H2O)n obtained by considering n = 2–7 and various geometrical arrangements. A total of seventy-seven O−H⋯O hydrogen bonds (HBs) were identified in the systems under consideration, and the examination of the electron density at the bond critical point (BCP) of these HBs revealed the existence of a great diversity of O−H⋯O interactions. Furthermore, the analysis of quantities, such as |V(r)|/G(r) and H(r), allowed a further description of the nature of analogous O−H⋯O interactions within each cluster. In the case of 2-D cyclic clusters, the HBs are nearly equivalent between them. However, significant differences among the O−H⋯O interactions were observed in 3-D clusters. The assessment of the source function (SF) confirmed these findings. Finally, the ability of SF to decompose the electron density (ρ) into atomic contributions allowed the evaluation of the localized or delocalized character of these contributions to ρ at the BCP associated to the different HBs, revealing that weak O−H⋯O interactions have a significant spread of the atomic contributions, whereas strong interactions have more localized atomic contributions. These observations suggest that the nature of the O−H⋯O hydrogen bond in water clusters is determined by the inductive effects originated by the different spatial arrangements of the water molecules in the studied clusters.
Ozone in Chemotherapy-Induced Peripheral Neuropathy—Current State of Art, Possibilities, and Perspectives
Authors: Szklener Katarzyna , Rudzińska Anna , Juchaniuk Pola , Kabała Zuzanna , Mańdziuk Sławomir
Published: March 2023

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most detrimental toxicity to a patient’s quality of life. Pathophysiological mechanisms involved in CIPN pathogenesis are complex, multifactorial, and only partially examined. They are suspected to be associated with oxidative stress (OS), mitochondrial dysfunction, ROS-induced apoptosis, myelin sheath and DNA damage, and immunological and inflammatory processes. Unfortunately, medications commonly used for the management of other neuropathic pain syndromes, including gabapentinoids, opioids, and tricyclic antidepressants (such as desipramine and nortriptyline), do not bring satisfactory results in CIPN. The aim of this review is to evaluate the existing literature on the potential use of medical ozone as a treatment for CIPN. This paper would explore the potential therapeutic benefits of medical ozone. The review would evaluate the existing literature on the use of medical ozone in other contexts, as well as its potential application in treating CIPN. The review would also suggest possible research methods, such as randomized controlled trials, to evaluate the efficacy of medical ozone as a treatment for CIPN. Medical ozone has been used to disinfect and treat diseases for over 150 years. The effectiveness of ozone in treating infections, wounds, and a variety of diseases has been well documented. Ozone therapy is also documented to inhibit the growth of human cancer cells and has antioxidative and anti-inflammatory effects. Due to its ability to modulate oxidative stress, inflammation, and ischemia/hypoxia, ozone may have a potentially valuable effect on CIPN.
Convenient and Sensitive Measurement of Lactosylceramide Synthase Activity Using Deuterated Glucosylceramide and Mass Spectrometry
Authors: Dei Cas Michele , Montavoci Linda , Casati Sara , Malagolini Nadia , Dall’Olio Fabio , Trinchera Marco
Published: March 2023

Lactosylceramide is necessary for the biosynthesis of almost all classes of glycosphingolipids and plays a relevant role in pathways involved in neuroinflammation. It is synthesized by the action of galactosyltransferases B4GALT5 and B4GALT6, which transfer galactose from UDP-galactose to glucosylceramide. Lactosylceramide synthase activity was classically determined in vitro by a method based on the incorporation of radiolabeled galactose followed by the chromatographic separation and quantitation of the product by liquid scintillation counting. Here, we used deuterated glucosylceramide as the acceptor substrate and quantitated the deuterated lactosylceramide product by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We compared this method with the classical radiochemical method and found that the reactions have similar requirements and provide comparable results in the presence of high synthase activity. Conversely, when the biological source lacked lactosylceramide synthase activity, as in the case of a crude homogenate of human dermal fibroblasts, the radiochemical method failed, while the other provided a reliable measurement. In addition to being very accurate and sensitive, the proposed use of deuterated glucosylceramide and LC-MS/MS for the detection of lactosylceramide synthase in vitro has the relevant advantage of avoiding the costs and discomforts of managing radiochemicals.
Serum CXCL5 Detects Early Hepatocellular Carcinoma and Indicates Tumor Progression
Authors: Laschtowitz Alena , Lambrecht Joeri , Puengel Tobias , Tacke Frank , Mohr Raphael
Published: March 2023

Chemokines or chemotactic cytokines play a pivotal role in the immune pathogenesis of liver cirrhosis and hepatocellular carcinoma (HCC). Nevertheless, comprehensive cytokine profiling data across different etiologies of liver diseases are lacking. Chemokines might serve as diagnostic and prognostic biomarkers. In our study, we analyzed serum concentrations of 12 inflammation-related chemokines in a cohort of patients (n = 222) with cirrhosis of different etiologies and/or HCC. We compared 97 patients with cirrhosis and treatment-naïve HCC to the chemokine profile of 125 patients with cirrhosis but confirmed absence of HCC. Nine out of twelve chemokines were significantly elevated in sera of cirrhotic patients with HCC compared to HCC-free cirrhosis controls (CCL2, CCL11, CCL17, CCL20, CXCL1, CXCL5, CXCL9, CXCL10, CXCL11). Among those, CXCL5, CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with early HCC according to the Barcelona Clinic Liver Cancer (BCLC) stages 0/A compared to cirrhotic controls without HCC. In patients with HCC, CXCL5 serum levels were associated with tumor progression, and levels of CCL20 and CXCL8 with macrovascular invasion. Importantly, our study identified CXCL5, CXCL9, and CXCL10 as universal HCC markers, independent from underlying etiology of cirrhosis. In conclusion, regardless of the underlying liver disease, patients with cirrhosis share an HCC-specific chemokine profile. CXCL5 may serve as a diagnostic biomarker in cirrhotic patients for early HCC detection as well as for tumor progression.
Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD)
Authors: Fontaine Valérie , Balducci Christine , Dinan Laurence , Monteiro Elodie , Boumedine Thinhinane , Fournié Mylène , Nguyen Vincent , Guibout Louis , Clatot Justine , Latil Mathilde , Veillet Stanislas , Sahel José-Alain , Lafont René , Dilda Pierre J. , Camelo Serge
Published: March 2023

9′-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4−/− Rdh8−/− double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD.
DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis
Authors: Blatkiewicz Małgorzata , Sielatycka Katarzyna , Piotrowska Katarzyna , Kilańczyk Ewa
Published: March 2023

Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic liver disease that begins with immune-mediated bile duct damage, and is followed by liver fibrosis, and finally, cirrhosis. PBC primarily affects postmenopausal women, with an average age of diagnosis of 65 years, but younger women are also affected. Here, we analyzed the levels of DHEA, estradiol (E2), and estriol (E3) in the PBC sera of females at an age of diagnosis under 40 (n = 37) and above 65 (n = 29). Our results indicate that in PBC patients at an age of diagnosis under 40, E2 was significantly lower compared to that in healthy women. In contrast, the levels of DHEA and E3 were in a normal range. Furthermore, ELISA assays revealed that in PBC patients at an age of diagnosis above 65, the levels of DHEA, E2, and E3 significantly declined in comparison to those in younger patients. In addition, flow cytometry analysis showed that the level of IL-8 significantly decreased while the level of TNF-α increased in older PBC patients compared to younger ones. Moreover, we showed for the first time that the sulfonated form of DHEA, DHEA-S, reduces the levels of both pro-inflammatory interleukins, IL-8 and TNF-α, in PBC-like cholangiocytes (H69-miR506), while it diminishes the level of the pro-fibrotic interleukin, IL-13, in hepatocytes (Hep-G2). Finally, we demonstrated that the expression of the pro-fibrotic agent TGF-β significantly increased in both the early (F0–F3) and cirrhotic (F4) stages of PBC, and this elevation was accompanied by higher α-SMA expression.
Non-Protein Thiol Compounds and Antioxidant Responses Involved in Bryophyte Heavy-Metal Tolerance
Authors: Salbitani Giovanna , Maresca Viviana , Cianciullo Piergiorgio , Bossa Rosanna , Carfagna Simona , Basile Adriana
Published: March 2023

Heavy-metal pollution represents a problem which has been widely discussed in recent years. The biological effects of heavy metals have been studied in both animals and plants, ranging from oxidative stress to genotoxicity. Plants, above all metal-tolerant species, have evolved a wide spectrum of strategies to counteract exposure to toxic metal concentrations. Among these strategies, the chelation and vacuolar sequestration of heavy metals are, after cell-wall immobilization, the first line of defence that prevent heavy metals from interacting with cell components. Furthermore, bryophytes activate a series of antioxidant non-enzymatic and enzymatic responses to counteract the effects of heavy metal in the cellular compartments. In this review, the role of non-protein thiol compounds and antioxidant molecules in bryophytes will be discussed.
Soybean Mosaic Virus 6K1 Interactors Screening and GmPR4 and GmBI1 Function Characterization
Authors: Hu Ting , Luan Hexiang , Wang Liqun , Ren Rui , Sun Lei , Yin Jinlong , Liu Hui , Jin Tongtong , Li Bowen , Li Kai , Zhi Haijian
Published: March 2023

Host proteins are essential during virus infection, and viral factors must target numerous host factors to complete their infectious cycle. The mature 6K1 protein of potyviruses is required for viral replication in plants. However, the interaction between 6K1 and host factors is poorly understood. The present study aims to identify the host interacting proteins of 6K1. Here, the 6K1 of Soybean mosaic virus (SMV) was used as the bait to screen a soybean cDNA library to gain insights about the interaction between 6K1 and host proteins. One hundred and twenty-seven 6K1 interactors were preliminarily identified, and they were classified into six groups, including defense-related, transport-related, metabolism-related, DNA binding, unknown, and membrane-related proteins. Then, thirty-nine proteins were cloned and merged into a prey vector to verify the interaction with 6K1, and thirty-three of these proteins were confirmed to interact with 6K1 by yeast two-hybrid (Y2H) assay. Of the thirty-three proteins, soybean pathogenesis-related protein 4 (GmPR4) and Bax inhibitor 1 (GmBI1) were chosen for further study. Their interactions with 6K1 were also confirmed by bimolecular fluorescence complementation (BiFC) assay. Subcellular localization showed that GmPR4 was localized to the cytoplasm and endoplasmic reticulum (ER), and GmBI1 was located in the ER. Moreover, both GmPR4 and GmBI1 were induced by SMV infection, ethylene and ER stress. The transient overexpression of GmPR4 and GmBI1 reduced SMV accumulation in tobacco, suggesting their involvement in the resistance to SMV. These results would contribute to exploring the mode of action of 6K1 in viral replication and improve our knowledge of the role of PR4 and BI1 in SMV response.
Macrophage-Specific Coxsackievirus and Adenovirus Receptor Deletion Enhances Macrophage M1 Polarity in CVB3-Induced Myocarditis
Authors: Shin Ha-Hyeon , Jeon Eun-Seok , Lim Byung-Kwan
Published: March 2023

The coxsackievirus and adenovirus receptor (CAR) is very well known as an epithelial tight junction and cardiac intercalated disc protein; it mediates attachment and infection via the coxsackievirus B3 (CVB3) and type 5 adenovirus. Macrophages play important roles in early immunity during viral infections. However, the role of CAR in macrophages is not well studied in relation to CVB3 infection. In this study, the function of CAR was observed in the Raw264.7 mouse macrophage cell line. CAR expression was stimulated by treatment with lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α). In thioglycollate-induced peritonitis, the peritoneal macrophage was activated and CAR expression was increased. The macrophage-specific CAR conditional knockout mice (KO) were generated from lysozyme Cre mice. The expression of inflammatory cytokine (IL-1β and TNF-α) was attenuated in the KO mice’s peritoneal macrophage after LPS treatment. In addition, the virus was not replicated in CAR-deleted macrophages. The organ virus replication was not significantly different in both wild-type (WT) and KO mice at days three and seven post-infection (p.i). However, the inflammatory M1 polarity genes (IL-1β, IL-6, TNF-α and MCP-1) were significantly increased, with increased rates of myocarditis in the heart of KO mice compared to those of WT mice. In contrast, type1 interferon (IFN-α and β) was significantly decreased in the heart of KO mice. Serum chemokine CXCL-11 was increased in the KO mice at day three p.i. compared to the WT mice. The attenuation of IFN-α and β in macrophage CAR deletion induced higher levels of CXCL-11 and more increased CD4 and CD8 T cells in KO mice hearts compared to those of WT mice at day seven p.i. These results demonstrate that macrophage-specific CAR deletion increased the macrophage M1 polarity and myocarditis in CVB3 infection. In addition, chemokine CXCL-11 expression was increased, and stimulated CD4 and CD8 T cell activity. Macrophage CAR may be important for the regulation of innate-immunity-induced local inflammation in CVB3 infection.
QoS-Aware Resource Management in 5G and 6G Cloud-Based Architectures with Priorities
Authors: Louvros Spiros (Spyridon) , Paraskevas Michael , Chrysikos Theofilos
Published: March 2023

Fifth-generation and more importantly the forthcoming sixth-generation networks have been given special care for latency and are designed to support low latency applications including a high flexibility New Radio (NR) interface that can be configured to utilize different subcarrier spacings (SCS), slot durations, special scheduling optional features (mini-slot scheduling), cloud- and virtual-based transport network infrastructures including slicing, and finally intelligent radio and transport packet retransmissions mechanisms. QoS analysis with emphasis on the determination of the transmitted packets’ average waiting time is therefore crucial for both network performance and user applications. Most preferred implementations to optimize transmission network rely on the cloud architectures with star network topology. In this paper, as part of our original and innovative contribution, a two-stage queue model is proposed and analytically investigated. Firstly, a two-dimension queue is proposed in order to estimate the expected delay on priority scheduling decisions over the IP/Ethernet MAC layer of IP packet transmissions between gNB and the core network. Furthermore, a one-dimension queue is proposed to estimate the average packet waiting time on the RLC radio buffer before being scheduled mainly due to excessive traffic load and designed transmission bandwidth availability.
Strategies for Enhancing Assessment Information Integrity in Mobile Learning
Authors: Kaisara Godwin , Bwalya Kelvin Joseph
Published: March 2023

Mobile learning is a global trend, which has become more widespread in the post-COVID-19 pandemic era. However, with the adoption of mobile learning comes new assessment approaches to evaluate the understanding of the acquired information and knowledge. Nevertheless, there is scant knowledge of how to enhance assessment information integrity in mobile learning assessments. Due to the importance of assessments in evaluating knowledge, integrity is the sine qua non of online assessments. This research focuses on the strategies universities could use to improve assessment information integrity. This research adopts a qualitative design, employing interviews with academics as well as teaching and learning support staff for data collection. The findings reveal five strategies that academics and support staff recommend to enhance assessment information integrity in mobile learning. The theoretical and practical implications are discussed, as well as future research directions.
Neutral W(V) Complexes Featuring the W2O2(µ-O)2 Core and Amino Acids or EDTA Derivatives as Ligands: Synthesis and Structural Characterization
Authors: Varbanov Hristo P. , Belaj Ferdinand , Glasnov Toma , Herbert Simon , Brumby Thomas , Mösch-Zanetti Nadia C.
Published: March 2023

Multinuclear complexes of heavy metals, such as tungsten, have demonstrated considerable potential as candidates for advanced radiocontrast agents. Of particular interest is the development of stable non-ionic compounds with high metal content and reasonably low osmolality in solution. Accordingly, we have synthesized a series of neutral W(V) complexes that contain the W2O2(µ-O)2 core and amino acids or disubstituted EDTA derivatives as ligands. The compounds were prepared from the oxalatotungstate(V) complex via a convenient procedure utilizing microwave heating. Their detailed characterization was accomplished by electrospray ionization high-resolution mass spectrometry (ESI-HRMS), 1H and 13C NMR spectroscopy, elemental analysis, and X-ray crystallography. Further experiments to evaluate the utility of the complexes as radiocontrast media were precluded by their poor aqueous solubility.
Investigation on the Formation of Rare-Earth Metal Phenoxides via Metathesis
Authors: Wang Jintao , Pei Qijun , Yu Yang , Cui Jirong , Wang Shangshang , Tan Khai Chen , Guo Jiaquan , He Teng , Chen Ping
Published: March 2023

A number of alkali organometallic complexes with suitable thermodynamic properties and high capacity for hydrogen storage have been synthesized; however, few transition metal–organic complexes have been reported for hydrogen storage. Moreover, the synthetic processes of these transition metal–organic complexes via metathesis were not well characterized previously, leading to a lack of understanding of the metathesis reaction. In the present study, yttrium phenoxide and lanthanum phenoxide were synthesized via metathesis of sodium phenoxide with YCl3 and LaCl3, respectively. Quasi in situ NMR, UV-vis, and theoretical calculations were employed to characterize the synthetic processes and the final products. It is revealed that the electron densities of phenoxides in rare-earth phenoxides are lower than in sodium phenoxide due to the stronger Lewis acidity of Y3+ and La3+. The synthetic process may follow a pathway of stepwise formation of dichloride, monochloride, and chloride-free species. Significant decreases in K-band and R-band absorption were observed in UV-vis, which may be due to the weakened conjugation effect between O and the aromatic ring after rare-earth metal substitution. Two molecular structures, i.e., planar and nonplanar, are identified by theoretical calculations for each rare-earth phenoxide. Since these two structures have very close single-point energies, they may coexist in the materials.
Phenological Features of the Spongy Moth, Lymantria dispar (L.) (Lepidoptera: Erebidae), in the Northernmost Portions of Its Eurasian Range
Authors: Ponomarev Vasiliy I. , Klobukov Georgiy I. , Napalkova Viktoria V. , Akhanaev Yuriy B. , Pavlushin Sergey V. , Yakimova Maria E. , Subbotina Anna O. , Picq Sandrine , Cusson Michel , Martemyanov Vyacheslav V.
Published: March 2023

The spongy moth, Lymatria dispar, is a classic example of an invasive pest accidentally introduced from Europe to North America, where it has become one of the most serious forest defoliators, as in its native range. The present study was aimed at (i) identifying the current northern limit of L. dispar’s Eurasian range and exploring its northward expansion in Canada using pheromone trap data, and (ii) comparing northern Eurasian populations with those from central and southern regions with respect to male flight phenology, the sums of effective temperatures (SETs) above the 7 °C threshold necessary for development to the adult stage, and heat availability. We show that the range of L. dispar in Eurasia now reaches the 61st parallel, and comparisons with historical data identify the average speed of spread as 50 km/year. We also document the northern progression of L. dispar in southern Canada, where the actual northern boundary of its range remains to be identified. We show that the median date of male flight does not vary greatly between northern and southern regions of the spongy moth range in Eurasia despite climate differences. Synchronization of flight at different latitudes of the range is associated with an acceleration of larval development in northern Eurasian populations. Similar changes in developmental rate along a latitudinal gradient have not been documented for North American populations. Thus, we argue that this feature of spongy moths from northern Eurasia poses a significant invasive threat to North America in terms of enhanced risks for rapid northward range expansion.