bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Smartphone Addiction and Social Isolation among Jordanian Children and Adolescents Using SEM and ML
Authors: Abu-Taieh Evon M. , AlHadid Issam , Kaabneh Khalid , Alkhawaldeh Rami S. , Khwaldeh Sufian , Masa’deh Ra’ed , Alrowwad Ala’Aldin
Published: September 2022

Smartphone addiction has become a major problem for everyone. According to recent studies, a considerable number of children and adolescents are more attracted to smartphones and exhibit addictive behavioral indicators, which are emerging as serious social problems. The main goal of this study is to identify the determinants that influence children’s smartphone addiction and social isolation among children and adolescents in Jordan. The theoretical foundation of this study model is based on constructs adopted from the Technology Acceptance Model (TAM) (i.e., perceived ease of use and perceived usefulness), with social influence and trust adopted from the TAM extended model along with perceived enjoyment. In terms of methodology, the study uses data from 511 parents who responded via convenient sampling, and the data was collected via a survey questionnaire and used to evaluate the research model. To test the study hypotheses, the empirical validity of the research model was set up, and the data were analyzed with SPSS version 21.0 and AMOS 26 software. Structural equation modeling (SEM), confirmatory factor analysis (CFA), and machine learning (ML) methods were used to test the study hypotheses and validate the properties of the instrument items. The ML methods used are support vector machine (SMO), the bagging reduced error pruning tree (REPTree), artificial neural network (ANN), and random forest. Several major findings were indicated by the results: perceived usefulness, trust, and social influence were significant antecedent behavioral intentions to use the smartphone. Also, findings prove that behavioral intention is statistically supported to have a significant influence on smartphone addiction. Furthermore, the findings confirm that smartphone addiction positively influences social isolation among Jordanian children and adolescents. Yet, perceived ease of use and perceived enjoyment did not have a significant effect on behavioral intention to use the smartphone among Jordanian children and adolescents. The research contributes to the body of knowledge and literature by empirically examining and theorizing the implications of smartphone addiction on social isolation. Further details of the study contribution, as well as research future directions and limitations, are presented in the discussion section.
Nutritional Parameters in Colostrum of Different Mammalian Species
Authors: Polidori Paolo , Rapaccetti Roberta , Klimanova Yulia , Zhang Jing-Jing , Santini Giuseppe , Vincenzetti Silvia
Published: September 2022

Colostrum (or first milk) is the food produced by all the mothers in all specific mammalian species, ruminants, monogastric and marine mammalians for their newborns during the first 24–48 h post-partum. Colostrum provides to the neonate all essential nutrients necessary for the first week of life, but the effect of colostrum shows a long-term effect not limited to these first days. Colostrum is considered to be a safe and essential food for human consumption. Some young children can show at the beginning of their colostrum-based diet some side effects, such as nausea and flatulence, but they disappear quickly. In human colostrum, the immunoglobulins and lactoferrin determined show the ability to create natural immunity in newborns, reducing greatly the mortality rate in children. Recent studies suggest that bovine colostrum (BC) may be an interesting nutraceutical food, due to its ability in preventing and/or mitigating several diseases in newborns and adults. This review aims to show the nutraceutical and functional properties of colostrum produced by several mammalian species, describing the different colostrum bio-active molecules and reporting the clinical trials aimed to determine colostrum nutraceutical and therapeutic characteristics in human nutrition.
Non-Invasive Transcutaneous Spinal DC Stimulation as a Neurorehabilitation ALS Therapy in Awake G93A Mice: The First Step to Clinical Translation
Authors: Highlander Morgan M. , Elbasiouny Sherif M.
Published: September 2022

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. The primary outcomes were motor function and survival. Unfortunately, skin damage avoidance limited the strength of applied stimulation intensity, likewise limiting measurable primary effects. The second aim of this study was to determine which orientation of stimulation (anodal vs cathodal, which are expected to have opposing effects) is beneficial vs harmful in ALS. Despite the lack of measured primary effects, strong trends in survival of the anodal stimulation group, combined with an analysis of survival variance and correlations among symptoms, suggest anodal stimulation is harmful at symptom onset. Therefore, cathodal stimulation may be beneficial at symptom onset if a higher stimulation intensity can be safely achieved via subcutaneously implanted electrodes or alternative methods. Importantly, the many logistical, physical, and stimulation parameters explored in developing this novel non-invasive treatment paradigm on unanesthetized mice provide insight into an appropriate and feasible methodology for future tsDCS study designs and potential clinical translation.
Host–Pathogen Interactions of Marine Gram-Positive Bacteria
Authors: Gnanagobal Hajarooba , Santander Javier
Published: September 2022

Marine Gram-positive bacterial pathogens, including Renibacterium salmoninarum, Mycobacterium marinum, Nocardia seriolae, Lactococcus garvieae, and Streptococcus spp. cause economic losses in marine fish aquaculture worldwide. Comprehensive information on these pathogens and their dynamic interactions with their respective fish–host systems are critical to developing effective prophylactic measures and treatments. While much is known about bacterial virulence and fish immune response, it is necessary to synthesize the knowledge in terms of host–pathogen interactions as a centerpiece to establish a crucial connection between the intricate details of marine Gram-positive pathogens and their fish hosts. Therefore, this review provides a holistic view and discusses the different stages of the host–pathogen interactions of marine Gram-positive pathogens. Gram-positive pathogens can invade fish tissues, evade the fish defenses, proliferate in the host system, and modulate the fish immune response. Marine Gram-positive pathogens have a unique set of virulence factors that facilitate adhesion (e.g., adhesins, hemagglutination activity, sortase, and capsules), invasion (e.g., toxins, hemolysins/cytolysins, the type VII secretion system, and immune-suppressive proteins), evasion (e.g., free radical quenching, actin-based motility, and the inhibition of phagolysosomal fusion), and proliferation and survival (e.g., heme utilization and siderophore-mediated iron acquisition systems) in the fish host. After infection, the fish host initiates specific innate and adaptive immune responses according to the extracellular or intracellular mechanism of infection. Although efforts have continued to be made in understanding the complex interplay at the host–pathogen interface, integrated omics-based investigations targeting host–pathogen–marine environment interactions hold promise for future research.
Regenerative Potential of A Bovine ECM-Derived Hydrogel for Biomedical Applications
Authors: Di Francesco Dalila , Bertani Fabio , Fusaro Luca , Clemente Nausicaa , Carton Flavia , Talmon Maria , Fresu Luigia Grazia , Boccafoschi Francesca
Published: September 2022

Recent advancements in regenerative medicine have enhanced the development of biomaterials as multi-functional dressings, capable of accelerating wound healing and addressing the challenge of chronic wounds. Hydrogels obtained from decellularized tissues have a complex composition, comparable to the native extracellular environment, showing highly interesting characteristics for wound healing applications. In this study, a bovine pericardium decellularized extracellular matrix (dECM) hydrogel was characterized in terms of macromolecules content, and its immunomodulatory, angiogenic and wound healing potential has been evaluated. The polarization profile of human monocytes-derived macrophages seeded on dECM hydrogel was assessed by RT-qPCR. Angiogenic markers expression has been evaluated by Western blot and antibody array on cell lysates derived from endothelial cells cultured on dECM hydrogel, and a murine in vivo model of hindlimb ischemia was used to evaluate the angiogenic potential. Fibroblast migration was assessed by a transwell migration assay, and an in vivo murine wound healing model treated with dECM hydrogels was also used. The results showed a complex composition, of which the major component is collagen type I. The dECM hydrogel is biocompatible, able to drive M2 phenotype polarization, stimulate the expression of angiogenic markers in vitro, and prevent loss of functionality in hindlimb ischemia model. Furthermore, it drives fibroblast migration and shows ability to facilitate wound closure in vivo, demonstrating its great potential for regenerative applications.
Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives
Authors: Tanase Daniela Maria , Gosav Evelina Maria , Anton Madalina Ioana , Floria Mariana , Seritean Isac Petronela Nicoleta , Hurjui Loredana Liliana , Tarniceriu Claudia Cristina , Costea Claudia Florida , Ciocoiu Manuela , Rezus Ciprian
Published: September 2022

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through its microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds the quality of life of these patients. Considering DKD is the main cause of end-stage renal disease (ESRD) in developed countries, extensive research is currently investigating the matrix of DKD pathophysiology. Hyperglycemia, inflammation and oxidative stress (OS) are the main mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-β, NF-κB, MCP-1, VCAM-1, ICAM-1) and the activation of diverse pathways (e.g., PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state with impairment of the antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations in the renal filtration unit. Hitherto, a wide spectrum of pre-clinical and clinical studies shows the beneficial use of NRF2-inducing strategies, such as NRF2 activators (e.g., Bardoxolone methyl, Curcumin, Sulforaphane and their analogues), and other natural compounds with antioxidant properties in DKD treatment. However, limitations regarding the lack of larger clinical trials, solubility or delivery hamper their implementation for clinical use. Therefore, in this review, we will discuss DKD mechanisms, especially oxidative stress (OS) and NRF2/KEAP1/ARE involvement, while highlighting the potential of therapeutic approaches that target DKD via OS.
Role of Adiponectin Peptide I (APNp1) in Age-Related Macular Degeneration
Authors: Logan Connor , Lyzogubov Valeriy , Bora Nalini , Bora Puran
Published: September 2022

Age-related macular degeneration (AMD) is an eye disease that can cause central vision loss, particularly in the elderly population. There are 2 classes of AMD, wet-type and dry-type. Wet-type involves excess angiogenesis around the macula, referred to as choroidal neovascularization (CNV). This can result in leaky vessels, often causing more severe vision loss than dry-type AMD. Adiponectin peptide 1 (APNp1) has been shown to slow the progression of CNV. Here, we used a mouse model and FITC-labeled APNp1 to determine if APNp1 could be delivered effectively as an eye drop. Our experiment revealed that topically applied FITC-APNp1 could reach the macula of the eye, which is crucial for treating wet-type AMD. We also tested delivery of APNp1 via injection of an adeno-associated virus (AAV) vector in a mouse model of CNV. AAV is a harmless virus easy to manipulate and is very often used for protein or peptide deliveries. Results revealed an increase in the expression of APNp1 in the retina and choroid over a 28-day period. Finally, we investigated the mechanism by which APNp1 affects CNV by examining the expression of adiponectin receptor 1 (AdipoR1) and proliferating cell nuclear antigen (PCNA) in the retinal and choroidal tissue of the mouse eyes. AdipoR1 and PCNA were overexpressed in these tissues in mice with laser-induced CNV compared to naïve mice. Based on our data shown here, we think it will enhance our understanding of APNp1 as a therapeutic agent for wet-type AMD and possible treatment alternatives that could be more beneficial for patients.
The Key Elements for Biomolecules to Biomaterials and to Bioapplications
Authors: Yu Deng-Guang , Zhao Ping
Published: September 2022

Biomolecules, as molecules which have a bio-source or a certain bioapplication, are at present quickening the marching speed for benefiting people’s life and social progress [...]
A New Product of Bilirubin Degradation by H2O2 and Its Formation in Activated Neutrophils and in an Inflammatory Mouse Model
Authors: Yu Fei-Fei , Yuan Yao , Ao Yan , Hua Li , Wang Wu , Cao Yiyi , Xi Jing , Luan Yang , Hou Shangwei , Zhang Xin-Yu
Published: September 2022

Bilirubin (BR) is a tetrapyrrolic compound stemming from heme catabolism with diverse physiological functions. It can be oxidized by H2O2 to form several degradation products, some of which have been detected in vivo and may contribute to the pathogenesis of certain diseases. However, the oxidative degradation of BR is complex and the conditions that BR degradation occurs pathophysiologically remain obscure. Neutrophils are known to generate large amounts of reactive oxygen species, including H2O2, upon activation and they are mobilized to inflammatory sites; therefore, we hypothesized that activated neutrophils could cause BR degradation, which could occur at inflammatory sites. In the present study, we investigated BR degradation by H2O2 and identified hematinic acid (BHP1) and a new product BHP2, whose structure was characterized as 2,5-diformyl-4-methyl-1H-pyrrole-3-propanoic acid. An LC-MS/MS method for the quantitation of the two compounds was then established. Using the LC-MS/MS method, we observed the concentration-dependent formation of BHP1 and BHP2 in mouse neutrophils incubated with 10 and 30 μM of BR with the yields being 16 ± 3.2 and 31 ± 5.9 pmol/106 cells for BHP1, and 25 ± 4.4 and 71 ± 26 pmol/106 cells for BHP2, respectively. After adding phorbol 12-myristate 13-acetate, a neutrophil agonist, to 30 μM of BR-treated cells, the BHP1 yield increased to 43 ± 6.6 pmol/106 cells, whereas the BHP2 one decreased to 47 ± 9.2 pmol/106 cells. The two products were also detected in hemorrhagic skins of mice with dermal inflammation and hemorrhage at levels of 4.5 ± 1.9 and 0.18 ± 0.10 nmol/g tissue, respectively, which were significantly higher than those in the non-hemorrhagic skins. BHP2 was neurotoxic starting at 0.10 μM but BHP1 was not, as assessed using Caenorhabditis elegans as the animal model. Neutrophil-mediated BR degradation may be a universally pathophysiological process in inflammation and can be particularly important under pathological conditions concerning hemorrhage.
Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors
Authors: Nie Dengyun , Guo Ting , Yue Miao , Li Wenya , Zong Xinyu , Zhu Yinxing , Huang Junxing , Lin Mei
Published: September 2022

Cancer is a genetic mutation disease that seriously endangers the health and life of all human beings. As one of the most amazing academic achievements in the past decade, CRISPR/Cas9 technology has been sought after by many researchers due to its powerful gene editing capability. CRISPR/Cas9 technology shows great potential in oncology, and has become one of the most promising technologies for cancer genome-editing therapeutics. However, its efficiency and the safety issues of in vivo gene editing severely limit its widespread application. Therefore, developing a suitable delivery method for the CRISPR/Cas9 system is an urgent problem to be solved at present. Rapid advances in nanomedicine suggest nanoparticles could be a viable option. In this review, we summarize the latest research on the potential use of nanoparticle-based CRISPR/Cas9 systems in cancer therapeutics, in order to further their clinical application. We hope that this review will provide a novel insight into the CRISPR/Cas9 system and offer guidance for nanocarrier designs that will enable its use in cancer clinical applications.
“Mens Sana in Corpore Sano”: The Emerging Link of Motor Reserve with Motor and Cognitive Abilities and Compensatory Brain Networks in SCA2 Patients
Authors: Siciliano Libera , Olivito Giusy , Urbini Nicole , Silveri Maria Caterina , Leggio Maria
Published: September 2022

The ability to resiliently cope with neuropathological lesions is a key scientific concern. Accordingly, this study aims to investigate whether motor reserve (MR), likely to be boosted by exercise engagement in a lifetime, affects motor symptom severity, cognitive functioning, and functional brain networks in spinocerebellar ataxia type 2 (SCA2)—a cerebellar neurodegenerative disease. The MR of 12 SCA2 patients was assessed using the Motor Reserve Index Questionnaire (MRIq), developed ad hoc for estimating lifespan MR. The International Cooperative Ataxia Rating Scale was used to assess clinical motor features, and neuropsychological tests were used to evaluate cognitive functioning. Patients underwent an MRI examination, and network-based statistics (NBS) analysis was carried out to detect patterns of functional connectivity (FC). Significant correlations were found between MRIq measures and the severity of motor symptoms, educational and intellectual levels, executive function, and processing speed. NBS analysis revealed a higher FC within subnetworks consisting of specific cerebellar and cerebral areas. FC patterns were positively correlated with MRIq measures, likely indicating the identification of an MR network. The identified network might reflect a biomarker likely to underlie MR, influenced by education and cognitive functioning, and impacting the severity of motor symptoms.
Understanding Acquired Brain Injury: A Review
Authors: Goldman Liam , Siddiqui Ehraz Mehmood , Khan Andleeb , Jahan Sadaf , Rehman Muneeb U , Mehan Sidharth , Sharma Rajat , Budkin Stepan , Kumar Shashi Nandar , Sahu Ankita , Kumar Manish , Vaibhav Kumar
Published: September 2022

Any type of brain injury that transpires post-birth is referred to as Acquired Brain Injury (ABI). In general, ABI does not result from congenital disorders, degenerative diseases, or by brain trauma at birth. Although the human brain is protected from the external world by layers of tissues and bone, floating in nutrient-rich cerebrospinal fluid (CSF); it remains susceptible to harm and impairment. Brain damage resulting from ABI leads to changes in the normal neuronal tissue activity and/or structure in one or multiple areas of the brain, which can often affect normal brain functions. Impairment sustained from an ABI can last anywhere from days to a lifetime depending on the severity of the injury; however, many patients face trouble integrating themselves back into the community due to possible psychological and physiological outcomes. In this review, we discuss ABI pathologies, their types, and cellular mechanisms and summarize the therapeutic approaches for a better understanding of the subject and to create awareness among the public.
Diagnosis of Hymenoptera Venom Allergy: State of the Art, Challenges, and Perspectives
Authors: Matysiak Joanna , Matuszewska Eliza , Packi Kacper , Klupczyńska-Gabryszak Agnieszka
Published: September 2022

Hymenoptera venom allergy is the most common cause of anaphylaxis in adults and the second-most frequent in children. The proper diagnosis of this life-threatening allergy remains a challenge. This review focuses on the current knowledge regarding diagnostics of Hymenoptera venom allergy. The paper includes a brief description of the representatives of Hymenoptera order and the composition of their venoms. Then, diagnostic tests for allergy to Hymenoptera venom are described. Common diagnostic problems, especially double positivity in tests for IgE antibodies specific to honeybee and wasp venom, are also discussed. Special attention is paid to the search for new diagnostic capabilities using modern methodologies. Multidimensional molecular analysis offers an opportunity to characterize changes in body fluids associated with Hymenoptera venom allergy and yields a unique insight into the cell status. Despite recent developments in the diagnostics of Hymenoptera venom allergy, new testing methodologies are still needed to answer questions and doubts we have.
Myosins and MyomiR Network in Patients with Obstructive Hypertrophic Cardiomyopathy
Authors: Foglieni Chiara , Lombardi Maria , Lazzeroni Davide , Zerboni Riccardo , Lazzarini Edoardo , Bertoli Gloria , Pisano Annalinda , Girolami Francesca , Andolfo Annapaola , Magagnotti Cinzia , Peretto Giovanni , Sartorio Carmem L. , Olivotto Iacopo , La Canna Giovanni , Alfieri Ottavio , Rimoldi Ornella E. , Barile Lucio , d’Amati Giulia , Camici Paolo G.
Published: September 2022

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes (MYH7, MYH7B and MYLC2), and the MyomiR network (myosin-encoded microRNA (miRs) and long-noncoding RNAs (Mhrt)) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B, and MYLC2 were higher in HCM whilst MYH6, miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499-target genes, SOX6 and PTBP3, were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499, demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets.
Validating Causal Diagrams of Human Health Risks for Spaceflight: An Example Using Bone Data from Rodents
Authors: Reynolds Robert J. , Scott Ryan T. , Turner Russell T. , Iwaniec Urszula T. , Bouxsein Mary L. , Sanders Lauren M. , Antonsen Erik L.
Published: September 2022

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables.
Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation
Authors: Liu Naiyou , Bowen Charles M. , Shoja Mohammadali M. , Castro de Pereira Karen Larissa , Dongur Laxmi Priya , Saad Antonio , Russell William K. , Broderick Thomas Christopher , Fair Jeffrey H. , Fagg William Samuel
Published: September 2022

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab.
Heat Shock Protein 27 Affects Myeloid Cell Activation and Interaction with Prostate Cancer Cells
Authors: Singer Debora , Ressel Verena , Stope Matthias B. , Bekeschus Sander
Published: September 2022

Heat shock proteins are cytoprotective molecules induced by environmental stresses. The small heat shock protein 27 (Hsp27) is highly expressed under oxidative stress conditions, mediating anti-oxidative effects and blocking apoptosis. Since medical gas plasma treatment subjects cancer cells to a multitude of reactive oxygen species (ROS), inducing apoptosis and immunomodulation, probable effects of Hsp27 should be investigated. To this end, we quantified the extracellular Hsp27 in two prostate cancer cell lines (LNCaP, PC-3) after gas plasma-induced oxidative stress, showing a significantly enhanced release. To investigate immunomodulatory effects, two myeloid cell lines (THP-1 and HL-60) were also exposed to Hsp27. Only negligible effects on viability, intracellular oxidative milieu, and secretion profiles of the myeloid cells were found when cultured alone. Interestingly, prostate cancer-myeloid cell co-cultures showed altered secretion profiles with a significant decrease in vascular endothelial growth factor (VEGF) release. Furthermore, the myeloid surface marker profiles were changed, indicating an enhanced differentiation in co-culture upon Hsp27 treatment. Finally, we investigated morphological changes, proliferation, and interaction with prostate cancer cells, and found significant alterations in the myeloid cells, supporting the tendency to differentiate. Collectively, our results suggest an ambiguous effect of Hsp27 on myeloid cells in the presence of prostate cancer cells which needs to be further investigated.
Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients
Authors: Bratseth Vibeke , Nordeng Jostein , Helseth Ragnhild , Solheim Svein , Åkra Sissel , Arnesen Harald , Chiva-Blanch Gemma , Seljeflot Ingebjørg
Published: September 2022

Microvesicles (MVs) are actively secreted by cells. The NLRP3-inflammasome and the interleukin 6 (IL-6)-pathways are central in cardiovascular disease. Knowledge of how the inflammasome influences the MVs is limited. In a cross-sectional study, we assessed whether MVs in plasma associate with genes encoding inflammasome signalling in coronary thrombi. Moreover, any relationships between inflammasome activation and phosphatidylserine (PS) externalization, determined through Annexin V (AV+) labelling, and myocardial injury, assessed by cardiac troponin T (cTnT), were analysed. Intracoronary thrombi and blood samples from STEMI patients (n = 33) were investigated. mRNA of NLRP3, caspase-1, interleukin-1β (IL-1β), interleukin-18 (IL-18), IL-6, soluble IL-6-receptor (sIL-6R), and glycoprotein-130 (gp130) were isolated from the thrombi and relatively quantified by RT-PCR. MVs were analysed by flow cytometry. Total AV+ MVs, mainly reflecting hypercoagulability, correlated positively to NLRP3 gene expression (r = 0.545, p = 0.009). A similar pattern was seen for platelet, endothelial and leukocyte derived MVs, separately. The majority of the MVs were AV− (96%). Total and AV− MVs correlated inversely with IL-1β (r = −0.399 and −0.438, respectively, p < 0.05, both) and gp130 (r = −0.457 and −0.502, respectively, p < 0.05, both). No correlations between MVs and cTnT were observed. Our findings indicate an association between NLRP3-inflammasome in coronary thrombi and procoagulant AV+ MVs in STEMI patients. The inverse relationships between AV− MVs and the gene expression of inflammasome activation may indicate an immuno-dampening role of this subpopulation.
Calcium Overload or Underload? The Effects of Doxorubicin on the Calcium Dynamics in Guinea Pig Hearts
Authors: Wu Jingjing , Gao Linlin , Fan Hong , Liu Deming , Lin Mengxue , Zhu Ming , Deng Tian , Song Yuanlong
Published: September 2022

The severe doxorubicin (DOXO) side effect of cardiomyopathy limits it clinical application as an effective anticancer drug. Although Ca2+ overload was postulated as one of the mechanisms for this toxicity, its role was, however, disputable in terms of the contractile dysfunction. In this work, the dynamics of the intracellular Ca2+ signal were optically mapped in a Langendorff guinea pig heart. We found that DOXO treatment: (1) Delayed the activation of the Ca2+ signal. With the reference time set at the peak of the action potential (AP), the time lag between the peak of the Ca2+ signal and AP (Ca-AP-Lag) was significantly prolonged. (2) Slowed down the intracellular Ca2+ releasing and sequestering process. Both the maximum rising (MRV) and falling (MFV) velocity of the Ca2+ signal were decreased. (3) Shortened the duration of the Ca2+ signal in one cycle of Ca2+ oscillation. The duration of the Ca2+ signal at 50% amplitude (CaD50) was significantly shortened. These results suggested a reduced level of intracellular Ca2+ after DOXO treatment. Furthermore, we found that the effect of tachypacing was similar to that of DOXO, and, interestingly, DOXO exerted contradictory effects on the tachypaced hearts: it shortened the Ca-AP-Lag, accelerated the MRV and MFV, and prolonged the CaD50. We, therefore, concluded that DOXO had a different effect on intracellular Ca2+. It caused Ca2+ underload in hearts with sinus rhythm; this might relate to the contractile dysfunction in DOXO cardiomyopathy. It led to Ca2+ overload in the tachypaced hearts, which might contribute to the Ca2+-overload-related toxicity.
Design of a Variable Stiffness Gecko-Inspired Foot and Adhesion Performance Test on Flexible Surface
Authors: Yu Zhiwei , Fu Jiahui , Ji Yu , Zhao Benhua , Ji Aihong
Published: September 2022

Adhesion robots have broad application prospects in the field of spacecraft inspection, repair, and maintenance, but the stable adhesion and climbing on the flexible surface covering the spacecraft has not been achieved. The flexible surface is easily deformed when subjected to external force, which makes it difficult to ensure a sufficient contact area and then detach from it. To achieve stable attachment and easy detachment on the flexible surface under microgravity, an adhesion model is established based on the applied adhesive material, and the relationship between peeling force and the rigidity of the base material, peeling angle, and working surface stiffness is obtained. Combined with the characteristics of variable stiffness structure, the adhesion and detachment force of the foot is asymmetric. Inspired by the adhesion-detachment mechanism of the foot of the gecko, an active adhesion-detachment control compliant mechanism is designed to achieve the stable attachment and safe detachment of the foot on the flexible surface and to adapt to surfaces with different rigidity. The experimental results indicate that a maximum normal adhesion force of 7.66 N can be generated when fully extended, and the safe detachment is achieved without external force on a flexible surface. Finally, an air floating platform is used to build a microgravity environment, and the crawling experiment of a gecko-inspired robot on a flexible surface under microgravity is completed. The experimental results show that the gecko-inspired foot with variable stiffness can satisfy the requirements of stable crawling on flexible surfaces.
A Molecularly Imprinted Polypyrrole/GO@Fe3O4 Nanocomposite Modified Impedimetric Sensor for the Routine Monitoring of Lysozyme
Authors: Montoro-Leal Pablo , Frías Isaac A. M. , Vereda Alonso Elisa , Errachid Abdelhamid , Jaffrezic-Renault Nicole
Published: September 2022

Lysozyme (LYS) applications encompass anti-bacterial activity, analgesic, and anti-inflammatory effects. In this work, a porous framework that was based on the polymerization of pyrrole (PPy) in the presence of multi-functional graphene oxide/iron oxide composite (GO@Fe3O4) has been developed. Oxygen-containing and amine groups that were present in the nanocomposite were availed to assembly LYS as the molecularly imprinted polymer (MIP) template. The synthesized material (MIPPy/GO@Fe3O4) was electrodeposited on top of a gold microelectrode array. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were used to confirm the adequate preparation of GO@Fe3O4, and the characterization of the resulting molecularly imprinted electrochemical sensor (MIECS) was carried out by electrochemical impedance spectrometry (EIS), FT-IR analysis, and scanning electron microscopy (SEM). The impedimetric responses were analyzed mathematically by fitting to a Q(Q(RW)) equivalent circuit and quantitative determination of LYS was obtained in a linear range from 1 pg/mL to 0.1 µg/mL, presenting good precision (RSD ≈ 10%, n = 5) and low limit of detection (LOD = 0.009 pg/mL). The fabrication of this device is relatively simple, scalable, rapid, and economical, and the sensor can be used up to nine times without disintegration. The MIECS was successfully applied to the determination of LYS in fresh chicken egg white sample and in a commercial drug, resulting in a straightforward platform for the routine monitoring of LYS.
Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis
Authors: Zhang Yi-Bin , Zheng Feng , Stavrinou Lampis , Wang Hao-Jie , Fan Wen-Jian , Yao Pei-Sen , Lin Yuan-Xiang , Goldbrunner Roland , Zheng Shu-Fa , Stavrinou Pantelis , Kang De-Zhi
Published: September 2022

This study aimed to investigate the association between serum iron (SI) and postoperative delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed 985 consecutive adult patients diagnosed with aSAH. Demographic, clinical, and laboratory data were recorded. Univariate and multivariate analyses were employed to assess the association between SI and DCI. Propensity-score matching (PSM) analysis was implemented to reduce confounding. Postoperative DCI developed in 14.38% of patients. Lower SI upon admission was detected in aSAH patients with severe clinical conditions and severe aSAH. SI was negatively correlated with WFNS grade (r = −0.3744, p < 0.001) and modified Fisher (mFisher) grade (r = −0.2520, p < 0.001). Multivariable analysis revealed lower SI was independently associated with DCI [odds ratios (OR) 0.281, 95% confidence interval (CI) 0.177–0.448, p < 0.001], while WFNS grade and mFisher grade were not. The receiver-operating characteristics (ROC) curve analysis of SI for DCI gave an area under the curve (AUC) of 0.7 and an optimal cut-off of 7.5 μmol/L (95% CI 0.665 to 0.733, p < 0.0001). PSM demonstrated the DCI group had a significantly lower SI than the non-DCI group (10.91 ± 6.86 vs. 20.34 ± 8.01 μmol/L, p < 0.001). Lower SI remained a significant independent predictor for DCI and an independent poor prognostic factor of aSAH in multivariate analysis (OR 0.363, 95% CI 0.209–0.630, p < 0.001). The predictive performance of SI for poor outcome had a corresponding AUC of 0.718 after PSM. Lower SI upon admission is significantly associated with WFNS grade, mFisher grade, and predicts postoperative DCI and poor outcome at 90 days following aSAH.
New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders
Authors: Villa Chiara , Paudel Yam Nath , Piperi Christina
Published: September 2022

Neurodegenerative disorders remain a major burden for our society, affecting millions of people worldwide [...]
Safety Evaluation of Employing Temporal Interference Transcranial Alternating Current Stimulation in Human Studies
Authors: Piao Yi , Ma Ru , Weng Yaohao , Fan Chuan , Xia Xinzhao , Zhang Wei , Zeng Ginger Qinghong , Wang Yan , Lu Zhuo , Cui Jiangtian , Wang Xiaoxiao , Gao Li , Qiu Bensheng , Zhang Xiaochu
Published: September 2022

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min).
Clock Genes Profiles as Diagnostic Tool in (Childhood) ADHD—A Pilot Study
Authors: Dück Alexander , Reis Olaf , Wagner Henrike , Wunsch Katja , Häßler Frank , Kölch Michael , Astiz Mariana , Thome Johannes , Berger Christoph , Oster Henrik
Published: September 2022

Attention deficit hyperactivity disorder (ADHD) is a very common disorder in children and adults. A connection with sleep disorders, and above all, disorders of the circadian rhythm are the subject of research and debate. The circadian system can be represented on different levels. There have been a variety of studies examining 24-h rhythms at the behavioral and endocrine level. At the molecular level, these rhythms are based on a series of feedback loops of core clock genes and proteins. In this paper, we compared the circadian rhythms at the behavioral, endocrine, and molecular levels between children with ADHD and age- and BMI-matched controls, complementing the previous data in adults. In a minimally invasive setting, sleep was assessed via a questionnaire, actigraphy was used to determine the motor activity and light exposure, saliva samples were taken to assess the 24-h profiles of cortisol and melatonin, and buccal mucosa swaps were taken to assess the expression of the clock genes BMAL1 and PER2. We found significant group differences in sleep onset and sleep duration, cortisol secretion profiles, and in the expression of both clock genes. Our data suggest that the analysis of circadian molecular rhythms may provide a new approach for diagnosing ADHD in children and adults.
A Behavioral Approach to the Tourism Consumer Decisions of Generation Z
Authors: Puiu Silvia , Velea Liliana , Udristioiu Mihaela Tinca , Gallo Alessandro
Published: September 2022

The main objective of our research is to identify the impact of recycling and waste reduction behavior on the sustainable tourism decisions of Romanian youngsters (18–25 years old). We used the PLS-SEM method and introduced four variables in the model: sustainable tourism decisions, the interest in recycling, the interest in waste reduction, and the interest in natural and less polluted touristic destinations. The main results emphasize the direct influence of recycling and waste reduction behaviors on the decisions made by Generation Z regarding sustainable tourism and on their preference for destinations that are better preserved and less touched by human intervention. The novelty of our research consists of the fact that we introduced variables such as waste reduction from the perspective of tourists because most studies address it as a management approach of the companies in the tourism sector. The findings are useful for managers in the tourism sector to create better strategies for attracting the younger generation who are preoccupied by environmental issues and sustainability in general.
Influence of Support for Career Development Intelligence Building for College Graduates on their Job Performance: The Case of South Korea
Authors: Kim Eun Bee , Kim Jhong Yun (Joy)
Published: September 2022

This study conducted to identify the influence of support for career development intelligence building for college graduates, who are early career employees, and to prove the mediating effect of learning transfer and self-esteem. An analysis was conducted using the Graduate Occupational Mobility Survey panel data from the Korea Employment Information Service. The data analysis was conducted using the SPSS21.0, AMOS22.0, and PROCESS macro programs. The findings are as follows. The influence of support for career development intelligence building on learning transfer is significantly positive, as is the influence of learning transfer on self-esteem. In addition, self-esteem had a significantly positive influence on job performance. However, the relationship between learning transfer and job performance was negative, and the relationship between support for career development intelligence building and self-esteem was insignificant. Lastly, the PROCESS macro analysis showed a mediating effect of learning transfer and self-esteem between support for career development intelligence building and job performance. Thus, it is suggested that support for career development intelligence building for early career employees should precede the development of specific programs to increase their self-esteem and enhance their job performance.
Freezing Effect of Enhancing Tubes in a Freeze-Sealing Pipe Roof Method Based on the Unsteady-State Conjugate Heat Transfer Model
Authors: Deng Shengjun , Hu Dong , She Siyuan , Hong Zequn , Hu Xiangdong , Zhou Feng
Published: September 2022

The freeze-sealing pipe roof (FSPR) method was applied as an innovative construction technology to the Gongbei Tunnel of the Hong Kong–Zhuhai–Macau Bridge. A freezing scheme involving master freezing tubes, enhancing freezing tubes, and limiting freezing tubes is the key component of the freezing effect of the FSPR method during the construction process under various working conditions. This is related to whether the thickness and temperature of the frozen soil meet the design requirements under various complex working conditions, and it is also related to frost heave control and energy saving. Based on the unsteady-state conjugate heat transfer model, different freezing schemes of enhancing freezing tubes—that is, the shape, layout, operating duration, and heat preservation—were simulated to analyze the freezing effect, which can be measured by the thickness of frozen soil around the steel pipes and the average temperature of the frozen soil curtain. The results show that the greater the contact area between the enhancing tube and the inner wall of the steel pipe, the better the freezing effect, and that the semicircle enhancing freezing tube scheme is superior to the other three shapes of freezing tubes. The arrangement of enhancing freezing tubes far away from the excavation surface, without heat preservation measures, has a better freezing effect due to the function of the hollow pipe as a freezing pipe. Moreover, the enhancing freezing tube can be operated intermittently to control frost heave. Our research simulated the temperature fields of different media—such as steel pipes, frozen soil, and air—providing a design basis for similar projects, such as the combination of the pipe-roofing method and artificial freezing method.