bluuebunny/crossref_metadata_2025 huggingface dataset:
Availability of Financial and Medical Resources for Screening Providers and Its Impact on Cancer Screening Uptake and Intervention Programs
Authors: Takahashi Koshi , Nakamura Sho , Watanabe Kaname , Sakaguchi Masahiko , Narimatsu Hiroto
Published: September 2022

Interventions for residents and medical/financial resources available to screening providers can improve cancer screening rates. Yet the mechanisms by which the interactions of these factors affect the screening rates remain unknown. This study employed structural equation modeling to analyze the mechanisms underlying these factors. Data for Japanese municipalities’ medical/financial status, their implementation of screening interventions, and the number of municipality-based cancer screening appointments from April 2016 to March 2017 were obtained from an open database. Five cancer screenings were included: gastric, lung, colorectal, breast, and cervical cancer screening; all are nationally recommended for population screening in Japan. We defined two latent variables, namely, intervention for residents and medical/financial resources, and then analyzed the relationships between these variables and screening rates using structural equation modeling. Models were constructed for gastric, lung, and breast cancer screening, and similar relationships were observed. With these cancer types, medical/financial resources affected the intervention for residents, directly affecting screening rates. One limitation of this study is that it only included screening by municipalities, which may cause selection bias. In conclusion, financial pressures and lack of medical resources may cause a reduction in screening intervention programs, leading to stagnant screening rates. Ensuring consistent implementation of interventions for residents may improve local and regional cancer screening rates.
Aldehyde Dehydrogenase 2 Activator Augments the Beneficial Effects of Empagliflozin in Mice with Diabetes-Associated HFpEF
Authors: Pan Guodong , Roy Bipradas , Giri Shailendra , Lanfear David E. , Thandavarayan Rajarajan A. , Guha Ashrith , Ortiz Pablo A. , Palaniyandi Suresh Selvaraj
Published: September 2022

To ameliorate diabetes mellitus-associated heart failure with preserved ejection fraction (HFpEF), we plan to lower diabetes-mediated oxidative stress-induced 4-hydroxy-2-nonenal (4HNE) accumulation by pharmacological agents that either decrease 4HNE generation or increase its detoxification.A cellular reactive carbonyl species (RCS), 4HNE, was significantly increased in diabetic hearts due to a diabetes-induced decrease in 4HNE detoxification by aldehyde dehydrogenase (ALDH) 2, a cardiac mitochondrial enzyme that metabolizes 4HNE. Therefore, hyperglycemia-induced 4HNE is critical for diabetes-mediated cardiotoxicity and we hypothesize that lowering 4HNE ameliorates diabetes-associated HFpEF. We fed a high-fat diet to ALDH2*2 mice, which have intrinsically low ALDH2 activity, to induce type-2 diabetes. After 4 months of diabetes, the mice exhibited features of HFpEF along with increased 4HNE adducts, and we treated them with vehicle, empagliflozin (EMP) (3 mg/kg/d) to reduce 4HNE and Alda-1 (10 mg/kg/d), and ALDH2 activator to enhance ALDH2 activity as well as a combination of EMP + Alda-1 (E + A), via subcutaneous osmotic pumps. After 2 months of treatments, cardiac function was assessed by conscious echocardiography before and after exercise stress. EMP + Alda-1 improved exercise tolerance, diastolic and systolic function, 4HNE detoxification and cardiac liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathways in ALDH2*2 mice with diabetes-associated HFpEF. This combination was even more effective than EMP alone. Our data indicate that ALDH2 activation along with the treatment of hypoglycemic agents may be a salient strategy to alleviate diabetes-associated HFpEF.
Mechanism and Function of Circular RNA in Regulating Solid Tumor Radiosensitivity
Authors: Huang Junchao , Sun Huihui , Chen Zike , Shao Yingjie , Gu Wendong
Published: September 2022

Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current bottleneck in the development of radiation oncology. Circular RNAs (circRNAs) are a special class of endogenous non-coding RNAs. Numerous studies have shown that circRNAs have shown great potential in regulating the biological functions of tumors, including proliferation, migration, invasion, and treatment resistance, and that differences in their expression levels are closely related to the clinical prognosis of tumor patients. This review systematically compares the mechanisms of circRNAs in the process of tumor development and radiosensitivity and provides insight into the clinical translation of circRNAs in radiotherapy.
Effects of Rhizosphere Bacteria on Strawberry Plants (Fragaria × ananassa Duch.) under Water Deficit
Authors: Paliwoda Dominika , Mikiciuk Grzegorz , Mikiciuk Małgorzata , Kisiel Anna , Sas-Paszt Lidia , Miller Tymoteusz
Published: September 2022

Due to the observed climate warming, water deficiency in soil is currently one of the most important stressors limiting the size and quality of plant crops. Drought stress causes a number of morphological, physiological, and biochemical changes in plants, limiting their growth, development, and yield. Innovative methods of inducing resistance and protecting plants against stressors include the inoculation of crops with beneficial microorganisms isolated from the rhizosphere of the plant species to which they are to be applied. The aim of the present study was to evaluate 12 different strains of rhizosphere bacteria of the genera Pantoea, Bacillus, Azotobacter, and Pseudomonas by using them to inoculate strawberry plants and assessing their impact on mitigating the negative effects of drought stress. Bacterial populations were assessed by estimates of their size based on bacterial counts in the growth substrate and with bioassays for plant growth-promoting traits. The physiological condition of strawberry plants was determined based on the parameters of chlorophyll fluorescence. The usefulness of the test methods used to assess the influence of plant inoculation with rhizosphere bacteria on the response of plants growing under water deficit was also evaluated. A two-factor experiment was performed in a complete randomization design. The first experimental factor was the inoculation of plant roots with rhizosphere bacteria. The second experimental factor was the different moisture content of the growth substrate. The water potential was maintained at −10 to −15 kPa under control conditions, and at −40 to −45 kPa under the conditions of water deficit in the substrate. The tests on strawberry plants showed that the highest sensitivity to water deficiency, and thus the greatest usefulness for characterizing water stress, was demonstrated by the following indices of chlorophyll “a” fluorescence: FM, FV, FV/FM, PI, and Area. Based on the assessment of the condition of the photosynthetic apparatus and the analysis of chlorophyll “a” fluorescence indices, including hierarchical cluster analysis, the following strains of rhizosphere bacteria were found to have favorable effects on strawberry plants under water deficit: the Bacillus sp. strains DLGB2 and DKB26 and the Pantoea sp. strains DKB63, DKB70, DKB68, DKB64, and DKB65. In the tests, these strains of Bacillus sp. exhibited a common trait—the ability to produce siderophores, while those of Pantoea sp. were notable for phosphate mobilization and ACCD activity.
Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy
Authors: Díaz Martha Lucía , Burgess Karl , Burchmore Richard , Gómez María Adelaida , Gómez-Ochoa Sergio Alejandro , Echeverría Luis Eduardo , Morillo Carlos , González Clara Isabel
Published: September 2022

Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.
Novel Formulations Containing Fluorescent Sensors to Improve the Resolution of 3D Prints
Authors: Topa-Skwarczyńska Monika , Świeży Andrzej , Krok Dominika , Starzak Katarzyna , Niezgoda Paweł , Oksiuta Bartosz , Wałczyk Weronika , Ortyl Joanna
Published: September 2022

Three-dimensional printing in SLA (stereolithography) and DLP (digital light processing) technologies has recently been experiencing a period of extremely rapid development. This is due to the fact that researchers recognise the many advantages of 3D printing, such as the high resolution and speed of the modelling and printing processes. However, there is still a search for new resin formulations dedicated to specific 3D printers allowing for high-resolution prints. Therefore, in the following paper, the effects of dyes such as BODIPY, europium complex, and Coumarin 1 added to light-cured compositions polymerised according to the radical mechanism on the photopolymerisation process speed, polymerisation shrinkage, and the final properties of the printouts were investigated. The kinetics of the photopolymerisation of light-cured materials using real-time FT-IR methods, as well as printouts that tangibly demonstrate the potential application of 3D printing technology in Industry 4.0, were examined. These studies showed that the addition of dyes has an effect on obtaining fluorescent prints with good resolution.
LPS-Induced Coagulation and Neuronal Damage in a Mice Model Is Attenuated by Enoxaparin
Authors: Berkowitz Shani , Gofrit Shany Guly , Aharoni Shay Anat , Golderman Valery , Qassim Lamis , Goldberg Zehavit , Dori Amir , Maggio Nicola , Chapman Joab , Shavit-Stein Efrat
Published: September 2022

Background. Due to the interactions between neuroinflammation and coagulation, the neural effects of lipopolysaccharide (LPS)-induced inflammation (1 mg/kg, intraperitoneal (IP), n = 20) and treatment with the anti-thrombotic enoxaparin (1 mg/kg, IP, 15 min, and 12 h following LPS, n = 20) were studied in C57BL/6J mice. Methods. One week after LPS injection, sensory, motor, and cognitive functions were assessed by a hot plate, rotarod, open field test (OFT), and Y-maze. Thrombin activity was measured with a fluorometric assay; hippocampal mRNA expression of coagulation and inflammation factors were measured by real-time-PCR; and serum neurofilament-light-chain (NfL), and tumor necrosis factor-α (TNF-α) were measured by a single-molecule array (Simoa) assay. Results. Reduced crossing center frequency was observed in both LPS groups in the OFT (p = 0.02), along with a minor motor deficit between controls and LPS indicated by the rotarod (p = 0.057). Increased hippocampal thrombin activity (p = 0.038) and protease-activated receptor 1 (PAR1) mRNA (p = 0.01) were measured in LPS compared to controls, but not in enoxaparin LPS-treated mice (p = 0.4, p = 0.9, respectively). Serum NfL and TNF-α levels were elevated in LPS mice (p < 0.05) and normalized by enoxaparin treatment. Conclusions. These results indicate that inflammation, coagulation, neuronal damage, and behavior are linked and may regulate each other, suggesting another pharmacological mechanism for intervention in neuroinflammation.
Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2
Authors: Timchenko Lubov
Published: September 2022

Myotonic Dystrophies type 1 (DM1) and type 2 (DM2) are complex multisystem diseases without disease-based therapies. These disorders are caused by the expansions of unstable CTG (DM1) and CCTG (DM2) repeats outside of the coding regions of the disease genes: DMPK in DM1 and CNBP in DM2. Multiple clinical and molecular studies provided a consensus for DM1 pathogenesis, showing that the molecular pathophysiology of DM1 is associated with the toxicity of RNA CUG repeats, which cause multiple disturbances in RNA metabolism in patients’ cells. As a result, splicing, translation, RNA stability and transcription of multiple genes are misregulated in DM1 cells. While mutant CCUG repeats are the main cause of DM2, additional factors might play a role in DM2 pathogenesis. This review describes current progress in the translation of mechanistic knowledge in DM1 and DM2 to clinical trials, with a focus on the development of disease-specific therapies for patients with adult forms of DM1 and congenital DM1 (CDM1).
FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer
Authors: Moes-Sosnowska Joanna , Skupinska Monika , Lechowicz Urszula , Szczepulska-Wojcik Ewa , Skronska Paulina , Rozy Adriana , Stepniewska Aneta , Langfort Renata , Rudzinski Piotr , Orlowski Tadeusz , Popiel Delfina , Stanczak Aleksandra , Wieczorek Maciej , Chorostowska-Wynimko Joanna
Published: September 2022

While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3–IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1–3 and amplification of FGFR1 were also analyzed. FGFR1 and FGFR4 median gene expression was significantly (p < 0.001) decreased in tumors compared with normal tissue. Increased FGFR3 expression enhanced the recurrence risk (hazard ratio 4.72, p = 0.029), while high FGFR4 expression was associated with lymph node metastasis (p = 0.036). Enhanced FGFR1 gene expression was correlated with FGFR1 protein overexpression (r = 0.75, p = 0.0003), but not with FGFR1 amplification. NGS revealed known pathogenic FGFR2,3 variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with FGFR1,2 variants of uncertain significance not previously reported in Sq-NSCLC. These findings expand our knowledge of the Sq-NSCLC molecular background and show that combining different methods increases the rate of FGFR aberrations detection, which may improve patient selection for FGFRi treatment.
Early Rehabilitation Exercise after Stroke Improves Neurological Recovery through Enhancing Angiogenesis in Patients and Cerebral Ischemia Rat Model
Authors: Geng Huixia , Li Min , Tang Jing , Lv Qing , Li Ruiling , Wang Lai
Published: September 2022

Among cerebrovascular diseases, ischemic stroke is a leading cause of mortality and disability. Thrombolytic therapy with tissue plasminogen activator is the first choice for clinical treatment, but its use is limited due to the high requirements of patient characteristics. Therefore, the choice of neurological rehabilitation strategies after stroke is an important prevention and treatment strategy to promote the recovery of neurological function in patients. This study shows that rehabilitation exercise 24 h after stroke can significantly improve the neurological function (6.47 ± 1.589 vs. 3.21 ± 1.069 and 0.76 ± 0.852), exercise ability (15.68 ± 5.95 vs. 162.32 ± 9.286 and 91.18 ± 7.377), daily living ability (23.37 ± 5.196 vs. 66.95 ± 4.707 and 6.55 ± 2.873), and quality of life (114.39 ± 7.772 vs. 168.61 ± 6.323 and 215.95 ± 10.977) of patients after 1 month and 3 months, and its ability to promote rehabilitation is better than that of rehabilitation exercise administered to patients 72 h after stroke (p < 0.001). Animal experiments show that treadmill exercise 24 h after middle cerebral artery occlusion and reperfusion can inhibit neuronal apoptosis, reduce the volume of cerebral infarction on the third (15.04 ± 1.07% vs. 30.67 ± 3.06%) and fifth (8.33 ± 1.53% vs. 30.67 ± 3.06%) days, and promote the recovery of neurological function on the third (7.22 ± 1.478 vs. 8.28 ± 1.018) and fifth (4.44 ± 0.784 vs. 6.00 ± 0.767) days. Mechanistic studies have shown that treadmill exercise increases the density of microvessels, regulates angiogenesis, and promotes the recovery of nerve function by upregulating the expression of vascular endothelial growth factor and laminin. This study shows that rehabilitation exercise 24 h after stroke is conducive to promoting the recovery of patients’ neurological function, and provides a scientific reference for the clinical rehabilitation of stroke patients.
Significance of Capping Agents of Colloidal Nanoparticles from the Perspective of Drug and Gene Delivery, Bioimaging, and Biosensing: An Insight
Authors: Javed Rabia , Sajjad Anila , Naz Sania , Sajjad Humna , Ao Qiang
Published: September 2022

The over-growth and coagulation of nanoparticles is prevented using capping agents by the production of stearic effect that plays a pivotal role in stabilizing the interface. This strategy of coating the nanoparticles’ surface with capping agents is an emerging trend in assembling multipurpose nanoparticles that is beneficial for improving their physicochemical and biological behavior. The enhancement of reactivity and negligible toxicity is the outcome. In this review article, an attempt has been made to introduce the significance of different capping agents in the preparation of nanoparticles. Most importantly, we have highlighted the recent progress, existing roadblocks, and upcoming opportunities of using surface modified nanoparticles in nanomedicine from the drug and gene delivery, bioimaging, and biosensing perspectives.
Overexpression of a Fragaria vesca MYB Transcription Factor Gene (FvMYB82) Increases Salt and Cold Tolerance in Arabidopsis thaliana
Authors: Li Wenhui , Zhong Jiliang , Zhang Lihua , Wang Yu , Song Penghui , Liu Wanda , Li Xingguo , Han Deguo
Published: September 2022

The MYB transcription factor (TF) family is one of the largest transcription families in plants, which is widely involved in the responses to different abiotic stresses, such as salt, cold, and drought. In the present study, a new MYB TF gene was cloned from Fragaria vesca (a diploid strawberry) and named FvMYB82. The open reading frame (ORF) of FvMYB82 was found to be 960 bp, encoding 319 amino acids. Sequence alignment results and predictions of the protein structure indicated that the FvMYB82 contained the conserved R2R3-MYB domain. Subcellular localization analysis showed that FvMYB82 was localized onto the nucleus. Furthermore, the qPCR showed that the expression level of FvMYB82 was higher in new leaves and roots than in mature leaves and stems. When dealing with different stresses, the expression level of FvMYB82 in F. vesca seedlings changed markedly, especially for salt and cold stress. When FvMYB82 was introduced into Arabidopsis thaliana, the tolerances to salt and cold stress of FvMYB82-OE A. thaliana were greatly improved. When dealt with salt and cold treatments, compared with wild-type and unloaded line (UL) A. thaliana, the transgenic lines had higher contents of proline and chlorophyll, as well as higher activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). However, the transgenic A. thaliana had lower level of malondialdehyde (MDA) and electrolytic leakage (EL) than wild-type and UL A. thaliana under salt and cold stress. Meanwhile, FvMYB82 can also regulate the expression of downstream genes associated with salt stress (AtSnRK2.4, AtSnRK2.6, AtKUP6, and AtNCED3) and cold stress (AtCBF1, AtCBF2, AtCOR15a, and AtCOR78). Therefore, these results indicated that FvMYB82 probably plays an important role in the response to salt and cold stresses in A. thaliana by regulating downstream related genes.
Tumor-Promoting Activity and Proteomic Profiling of Cisplatin/Oxaliplatin-Derived DAMPs in Cholangiocarcinoma Cells
Authors: Songjang Worawat , Nensat Chatchai , Nernpermpisooth Nitirut , Seenak Porrnthanate , Pankhong Panyupa , Jumroon Noppadon , Kumphune Sarawut , Jiraviriyakul Arunya
Published: September 2022

Damage-associated molecular patterns (DAMPs) are well recognized as the molecular signature of immunogenic cell death (ICD). The efficacy of drug-induced ICD function may be impacted by the precise ratio between immunostimulatory and immunoinhibitory DAMPs. Tumor-derived DAMPs can activate tumor-expressed TLRs for the promotion of tumor cell motility, invasion, metastatic spread and resistance to chemotherapeutic treatment. Herein, drug-induced DAMPs’ expression and their role in tumor progression are utilized as one crucial point of evaluation regarding chemotherapeutic treatment efficacy in our study. Cisplatin and oxaliplatin, the conventional anticancer chemotherapy drugs, are emphasized as a cause of well-known DAMPs’ release from cholangiocarcinoma (CCA) cells (e.g., HSP family, S100, CRT and HMGB1), whereby they trigger Akt, ERK and Cyclin-D1 to promote tumor activities. These findings strengthen the evidence that DAMPs are not only involved in immunomodulation but also in tumor promotion. Therefore, DAMP molecules should be considered as either targets of cancer treatment or biomarkers to evaluate treatment efficacy and tumor recurrence.
Vesicular Glutamate Release from Feeder-FreehiPSC-Derived Neurons
Authors: Baldassari Simona , Cervetto Chiara , Amato Sarah , Fruscione Floriana , Balagura Ganna , Pelassa Simone , Musante Ilaria , Iacomino Michele , Traverso Monica , Corradi Anna , Scudieri Paolo , Maura Guido , Marcoli Manuela , Zara Federico
Published: September 2022

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons.
Diet-Induced Gut Barrier Dysfunction Is Exacerbated in Mice Lacking Cannabinoid 1 Receptors in the Intestinal Epithelium
Authors: Wiley Mark B. , DiPatrizio Nicholas V.
Published: September 2022

The gut barrier provides protection from pathogens and its function is compromised in diet-induced obesity (DIO). The endocannabinoid system in the gut is dysregulated in DIO and participates in gut barrier function; however, whether its activity is protective or detrimental for gut barrier integrity is unclear. We used mice conditionally deficient in cannabinoid receptor subtype-1 (CB1R) in the intestinal epithelium (intCB1−/−) to test the hypothesis that CB1Rs in intestinal epithelial cells provide protection from diet-induced gut barrier dysfunction. Control and intCB1−/− mice were placed for eight weeks on a high-fat/sucrose Western-style diet (WD) or a low-fat/no-sucrose diet. Endocannabinoid levels and activity of their metabolic enzymes were measured in the large-intestinal epithelium (LI). Paracellular permeability was tested in vivo, and expression of genes for gut barrier components and inflammatory markers were analyzed. Mice fed WD had (i) reduced levels of endocannabinoids in the LI due to lower activity of their biosynthetic enzymes, and (ii) increased permeability that was exacerbated in intCB1−/− mice. Moreover, intCB1−/− mice fed WD had decreased expression of genes for tight junction proteins and increased expression of inflammatory markers in LI. These results suggest that CB1Rs in the intestinal epithelium serve a protective role in gut barrier function in DIO.
Albumin as a Biomaterial and Therapeutic Agent in Regenerative Medicine
Authors: Kuten Pella Olga , Hornyák István , Horváthy Dénes , Fodor Eszter , Nehrer Stefan , Lacza Zsombor
Published: September 2022

Albumin is a constitutional plasma protein, with well-known biological functions, e.g., a nutrient for stem cells in culture. However, albumin is underutilized as a biomaterial in regenerative medicine. This review summarizes the advanced therapeutic uses of albumin, focusing on novel compositions that take advantage of the excellent regenerative potential of this protein. Albumin coating can be used for enhancing the biocompatibility of various types of implants, such as bone grafts or sutures. Albumin is mainly known as an anti-attachment protein; however, using it on implantable surfaces is just the opposite: it enhances stem cell adhesion and proliferation. The anticoagulant, antimicrobial and anti-inflammatory properties of albumin allow fine-tuning of the biological reaction to implantable tissue-engineering constructs. Another potential use is combining albumin with natural or synthetic materials that results in novel composites suitable for cardiac, neural, hard and soft tissue engineering. Recent advances in materials have made it possible to electrospin the globular albumin protein, opening up new possibilities for albumin-based scaffolds for cell therapy. Several described technologies have already entered the clinical phase, making good use of the excellent biological, but also regulatory, manufacturing and clinical features of serum albumin.
Rapid Evaporative Ionization Mass Spectrometry-Based Lipidomics for Identification of Canine Mammary Pathology
Authors: Mangraviti Domenica , Abbate Jessica Maria , Iaria Carmelo , Rigano Francesca , Mondello Luigi , Quartuccio Marco , Marino Fabio
Published: September 2022

The present work proposes the use of a fast analytical platform for the mass spectrometric (MS) profiling of canine mammary tissues in their native form for the building of a predictive statistical model. The latter could be used as a novel diagnostic tool for the real-time identification of different cellular alterations in order to improve tissue resection during veterinary surgery, as previously validated in human oncology. Specifically, Rapid Evaporative Ionization Mass Spectrometry (REIMS) coupled with surgical electrocautery (intelligent knife—iKnife) was used to collect MS data from histologically processed mammary samples, classified into healthy, hyperplastic/dysplastic, mastitis and tumors. Differences in the lipid composition enabled tissue discrimination with an accuracy greater than 90%. The recognition capability of REIMS was tested on unknown mammary samples, and all of them were correctly identified with a correctness score of 98–100%. Triglyceride identification was increased in healthy mammary tissues, while the abundance of phospholipids was observed in altered tissues, reflecting morpho-functional changes in cell membranes, and oxidized species were also tentatively identified as discriminant features. The obtained lipidomic profiles represented unique fingerprints of the samples, suggesting that the iKnife technique is capable of differentiating mammary tissues following chemical changes in cellular metabolism.
Identification of the Regulatory Targets of miR-3687 and miR-4417 in Prostate Cancer Cells Using a Proteomics Approach
Authors: Venz Simone , Junker Heike , Ultsch Erik , Hetke Franziska , Krüger Elke , Burchardt Martin , Caetano-Pinto Pedro , Roennau Cindy
Published: September 2022

MicroRNAs (miRNA) are ubiquitous non-coding RNAs that have a prominent role in cellular regulation. The expression of many miRNAs is often found deregulated in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). Although their expression can be associated with PCa and CRPC, their functions and regulatory activity in cancer development are poorly understood. In this study, we used different proteomics tools to analyze the activity of hsa-miR-3687-3p (miR-3687) and hsa-miR-4417-3p (miR-4417), two miRNAs upregulated in CRPC. PCa and CRPC cell lines were transfected with miR-3687 or miR-4417 to overexpress the miRNAs. Cell lysates were analyzed using 2D gel electrophoresis and proteins were subsequently identified using mass spectrometry (Maldi-MS/MS). A whole cell lysate, without 2D-gel separation, was analyzed by ESI-MS/MS. The expression of deregulated proteins found across both methods was further investigated using Western blotting. Gene ontology and cellular process network analysis determined that miR-3687 and miR-4417 are involved in diverse regulatory mechanisms that support the CRPC phenotype, including metabolism and inflammation. Moreover, both miRNAs are associated with extracellular vesicles, which point toward a secretory mechanism. The tumor protein D52 isoform 1 (TD52-IF1), which regulates neuroendocrine trans-differentiation, was found to be substantially deregulated in androgen-insensitive cells by both miR-3687 and miR-4417. These findings show that these miRNAs potentially support the CRPC by truncating the TD52-IF1 expression after the onset of androgen resistance.
Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies
Authors: Abdalla Osama Hasan Mustafa Hasan , Mascarenhas Brittany , Cheng Hai-Ying Mary
Published: September 2022

Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination. In this review, we summarize the roles that known E3 ubiquitin ligases play in the circadian clocks of two popular model organisms: mice and fruit flies. We also discuss emerging evidence that implicates the N-degron pathway, an alternative proteolytic system, in the regulation of circadian rhythms. We conclude the review with our perspectives on the potential for the proteolytic and non-proteolytic functions of E3 ubiquitin ligases within the circadian clock system.
Secondary Mitochondrial Dysfunction as a Cause of Neurodegenerative Dysfunction in Lysosomal Storage Diseases and an Overview of Potential Therapies
Authors: Stepien Karolina M. , Cufflin Neve , Donald Aimee , Jones Simon , Church Heather , Hargreaves Iain P.
Published: September 2022

Mitochondrial dysfunction has been recognised a major contributory factor to the pathophysiology of a number of lysosomal storage disorders (LSDs). The cause of mitochondrial dysfunction in LSDs is as yet uncertain, but appears to be triggered by a number of different factors, although oxidative stress and impaired mitophagy appear to be common inhibitory mechanisms shared amongst this group of disorders, including Gaucher’s disease, Niemann–Pick disease, type C, and mucopolysaccharidosis. Many LSDs resulting from defects in lysosomal hydrolase activity show neurodegeneration, which remains challenging to treat. Currently available curative therapies are not sufficient to meet patients’ needs. In view of the documented evidence of mitochondrial dysfunction in the neurodegeneration of LSDs, along with the reciprocal interaction between the mitochondrion and the lysosome, novel therapeutic strategies that target the impairment in both of these organelles could be considered in the clinical management of the long-term neurodegenerative complications of these diseases. The purpose of this review is to outline the putative mechanisms that may be responsible for the reported mitochondrial dysfunction in LSDs and to discuss the new potential therapeutic developments.
Modeling pKa of the Brønsted Bases as an Approach to the Gibbs Energy of the Proton in Acetonitrile
Authors: Glasovac Zoran , Kovačević Borislav
Published: September 2022

A simple but efficient computational approach to calculate pKa in acetonitrile for a set of phosphorus, nitrogen, and carbon bases was established. A linear function that describes relations between the calculated ΔG’a.sol(BH+) and pKa values was determined for each group of bases. The best model was obtained through the variations in the basis set, in the level of theory (density functionals or MP2), and in the continuum solvation model (IPCM, CPCM, or SMD). The combination of the IPCM/B3LYP/6-311+G(d,p) solvation approach with MP2/6-311+G(2df,p)//B3LYP/6-31G(d) gas-phase energies provided very good results for all three groups of bases with R2 values close to or above 0.99. Interestingly, the slopes and the intercepts of the obtained linear functions showed significant deviations from the theoretical values. We made a linear plot utilizing all the conducted calculations and all the structural variations and employed methods to prove the systematic nature of the intercept/slope dependence. The interpolation of the intercept to the ideal slope value enabled us to determine the Gibbs energy of the proton in acetonitrile, which amounted to −258.8 kcal mol−1. The obtained value was in excellent agreement with previously published results.
Anti-Inflammatory and Neuroprotective Effects of Morin in an MPTP-Induced Parkinson’s Disease Model
Authors: Hong Dong Geun , Lee Seulah , Kim Jaehoon , Yang Seonguk , Lee Myunggyo , Ahn Jinsook , Lee Haeseung , Chang Seung-Cheol , Ha Nam-Chul , Lee Jaewon
Published: September 2022

Neurodegenerative diseases such as Parkinson’s disease (PD) are known to be related to oxidative stress and neuroinflammation, and thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2′,3,4′,5,7-pentahydroxy flavone) is a flavonol with anti-oxidative and anti-inflammatory effects found in wines, herbs, and fruits. The present study was undertaken to determine whether a morin-containing diet has protective effects in an MPTP-induced mouse model of PD. Mice were fed a control or morin diet for 34 days, and then MPTP (30 mg/kg, i.p.) was administered daily for 5 days to induce a PD-like pathology. We found that dietary morin prevented MPTP-induced motor dysfunction and ameliorated dopaminergic neuronal damage in striatum (STR) and substantia nigra (SN) in our mouse model. Furthermore, MPTP-induced neuroinflammation was significantly reduced in mice fed morin. In vitro studies showed that morin effectively suppressed glial activations in primary microglia and astrocytes, and biochemical analysis and a docking simulation indicated that the anti-inflammatory effects of morin were mediated by blocking the extracellular signal-regulated kinase (ERK)-p65 pathway. These findings suggest that morin effectively inhibits glial activations and has potential use as a functional food ingredient with therapeutic potential for the treatment of PD and other neurodegenerative diseases associated with neuroinflammation.
Edge and Fog Computing Business Value Streams through IoT Solutions: A Literature Review for Strategic Implementation
Authors: Perifanis Nikolaos-Alexandros , Kitsios Fotis
Published: September 2022

Edge–fog computing and IoT have the ability to revolutionize businesses across all sectors and functions, from customer engagement to manufacturing, which is what makes them so fascinating and emerging. On the basis of research methodology by Webster and Watson (2020), 124 peer-reviewed articles were discussed. According to the literature, these technologies lead to reduced latency, costs, bandwidth, and disruption, but at the same time, they improved response time, compliance, security and greater autonomy. The results of this review revealed the open issues and topics which call for further research/examination in order for edge–fog computing to unveil new business value streams along with IoT capabilities for the organizations. Only by adopting and implementing precisely these revolutionary will new solutions organizations succeed in the digital transformation of the modern era. Despite the fact that they are cutting-edge solutions to business operations and knowledge creation, there are still practical implementation issues to be dealt with and a lack of experience in the strategic integration of the variable architectures, which hinder efforts to generate business value.
Effects of Fluctuating Thermal Regimes on Life History Parameters and Body Size of Ophraella communa
Authors: Zhao Chenchen , Chen Hongsong , Guo Jianying , Zhou Zhongshi
Published: September 2022

The beetle Ophraella communa is an effective biological control agent against the invasive common ragweed spread across various ecosystems with variable temperature ranges. The trend in climate change attributed to fluctuating temperatures and abrupt rainfalls is expected to continue. This study aimed to better understand the effects of thermal fluctuation on O. communa by exposing all their life stages to heat stress under different treatments. Repeated exposure to high temperatures, relative to constant milder temperatures, increased the duration of immature development, mean generation time, and the adult longevity, decreased the intrinsic rate of increase, finite rate of population increase, net reproductive rate, survival rate, overall longevity, body length, and mass of adults and positively affected overall fecundity by prolonging the oviposition period, biasing sex ratio towards females. After exposure to heat stress, the mating success and production of viable offspring were higher in O. communa. Our findings demonstrate that exposure to heat stress negatively affects ragweed beetles, but they were able to survive and reproduce.
Molecular Characterization of Native Entomopathogenic Fungi from Ambrosia Beetles in Hazelnut Orchards of Turkey and Evaluation of Their In Vitro Efficacy
Authors: Kushiyev Rahman , Tunçer Celal , Özdemir İsmail Oğuz , Erper İsmail , Kalendar Ruslan , Alkan Mehtap , Özer Göksel
Published: September 2022

Ambrosia beetles, Anisandrus dispar Fabricius, Xylosandrus germanus Blandford, and Xyleborinus saxesenii Ratzeburg (Coleoptera: Curculionidae: Scolytinae) are among the most significant hazelnut pests in Turkey. The control of these pests is difficult and expensive due to their biology. The present study aimed to isolate entomopathogenic fungi (EPF) from A. dispar, X. germanus, and X. saxesenii individuals that were obtained from the main hazelnut production areas of Turkey, characterize the EPF isolates using internal transcribed spacer (ITS)-DNA sequencing and iPBS profiling, and determine the efficacy of the isolates against A. dispar, X. germanus, and X. saxesenii under laboratory conditions. Phylogenetic analyses based on ITS revealed that the 47 native isolates were Beauveria bassiana (11), B. pseudobassiana (8), Cordyceps fumosorosea (6), Cordyceps farinosa (1), Akanthomyces lecanii (13), Purpureocillium lilacinum (3), Clonostachys rosea (2) and Metarhizium anisopliae (3). For the first time, the primer binding site (PBS) marker system, based on retrotransposons, was used to discriminate successfully among the EPF species. Some isolates of B. bassiana, B. pseudobassiana, C. fumosorosea, A. lecanii, and M. anisopliae caused 100% mortality of the beetle species within 7 to 9 days. The findings of this study indicated that some isolated entomopathogenic fungi provide an essential basis for the development of bioproducts, as well as a promising alternative method for controlling these ambrosia beetles.
Tomato Varieties Influence the Performance of Tamarixia triozae (Hymenoptera: Eulophidae) on Bactericera cockerelli (Hemiptera: Triozidae) Nymphs
Authors: Mayo-Hernández Juan , Vega-Chávez Jorge Luis , Hernández-Juárez Agustín , Rodríguez-Pagaza Yolanda , Valenzuela-Soto José Humberto , Flores-Olivas Alberto
Published: September 2022

The potato/tomato psyllid Bactericera cockerelli is the Candidatus Liberibacter solanacearum bacterium vector that causes diseases in Solanaceae crops. Pest control is based on synthetic chemical insecticides, plant extracts, and natural enemies such as parasitoids. Tamarixia triozae feeds on nymphs of B. cockerelli, reaching up to 95% parasitism. This work aimed to evaluate the parasitic performance of T. triozae on tomato leaves with B. cockerelli N3 nymphs, using two domesticated (Floradade and Micro-Tom) and one Wild tomato variety. Several assays were completed to identify the parasitoid attraction toward un-infested plants (healthy) and infested plants (damaged) of three varieties. Parasitism preference and “Y” tube olfactometer tests were performed, respectively. The parasitism of Tamarixia triozae showed a preference toward plants of the Floradade variety by 44% compared with the other two varieties (p = 0.0003). T. triozae was more attracted to damaged plants of the Wild variety (p = 0.0523). Healthy plants of Floradade and Micro-Tom varieties attracted a higher proportion of parasitoids, except in the Wild variety, where T. triozae was more attracted to damaged plants. Taken together, the results of this study show that the domestication degree in tomato plants positively influenced the interactions between tomato plants and the parasitoid, T. triozae.
Split Hopkinson Tension Bar and Universal Testing Machine for High-Speed X-ray Imaging of Materials under Tension
Authors: Jakkula Puneeth , Cohen Amitay , Lukić Bratislav , Levi-Hevroni David , Rack Alexander , Ganzenmüller Georg , Hiermaier Stefan
Published: September 2022

Studying the failure behaviour of engineered or natural materials under dynamic loading scenarios is of high importance, for example to investigate the fracture mechanics and to prevent catastrophic failures of constructions. When dynamic loading is coupled to high-speed X-ray imaging, not only surface information but images of the interior of the specimens during failure are accessible. Here, a custom designed Split Hopkinson Tension Bar (SHTB) coupled a Universal Testing Machine (UTM) has been developed, dedicated to study quasi-static and dynamic response using ultra-high speed X-ray phase contrast imaging. Both systems follow a compact design which allows them to be temporarily installed at a synchrotron beamline. A brief description of the installation and usage of these setups are outlined. Selected example applications outline the potential of these systems. Both systems can be considered for proposal experiments at beamline ID19 of the European synchrotron ESRF on request.
Composite Ceramics Based on Pastes Including Tricalcium Phosphate and an Aqueous Solution of Sodium Silicate
Authors: Kaimonov Maksim , Safronova Tatiana , Shatalova Tatiana , Filippov Yaroslav , Tikhomirova Irina , Lukina Yulia
Published: September 2022

Preceramic samples were prepared from pastes based on the aqueous solution of sodium silicate and tricalcium phosphate with a given molar ratio of (Na2O · 2,87SiO2)aq/Ca3(PO4)2 = 1:3 after drying at 24 °C and then 60 °C for 24 h. It established the dependence of the plastic strength of these pastes on both time and temperature and the possibility of using them for extrusion 3D printing. The phase composition of ceramic was represented by unreacted β-TCP (β-Ca3(PO4)2) and β-rhenanite (β-NaCaPO4) after heat treatment at 500 °C. Further, an increase in temperature up to 700 °C led to the appearing phase of silicon dioxide (SiO2) and up to 900 °C, of sodium calcium phosphate (Na3Ca6(PO4)5). After heat-treatment at 1100 °C, ceramic samples consisted of the β-TCP (β-Ca3(PO4)2), sodium calcium phosphate (Na3Ca6(PO4)5), silicon dioxide (SiO2) and β-wollastonite (β-CaSiO3). The bending and compressive strength of the ceramics rose with increasing temperature from ≈6.8 MPa and ≈31.1 MPa at 500 °C to ≈10.6 MPa and ≈43.5 MPa at 1100 °C. The obtained composite ceramics consisted of biocompatible phases that are widely studied in the literature and may be used as a biomaterial for the treatment of bone tissue defects.
Local Contrast-Based Pixel Ordering for Exact Histogram Specification
Authors: Inoue Kohei , Ono Naoki , Hara Kenji
Published: September 2022

Histogram equalization is one of the basic image processing tasks for contrast enhancement, and its generalized version is histogram specification, which accepts arbitrary shapes of target histograms including uniform distributions for histogram equalization. It is well known that strictly ordered pixels in an image can be voted to any target histogram to achieve exact histogram specification. This paper proposes a method for ordering pixels in an image on the basis of the local contrast of each pixel, where a Gaussian filter without approximation is used to avoid the duplication of pixel values that disturbs the strict pixel ordering. The main idea of the proposed method is that the problem of pixel ordering is divided into small subproblems which can be solved separately, and then the results are merged into one sequence of all ordered pixels. Moreover, the proposed method is extended from grayscale images to color ones in a consistent manner. Experimental results show that the state-of-the-art histogram specification method occasionally produces false patterns, which are alleviated by the proposed method. Those results demonstrate the effectiveness of the proposed method for exact histogram specification.