bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Renal Ischemic Preconditioning an Alternative to Ameliorate the Short- and Long-Term Consequences of Acute Kidney Injury?
Authors: Ortega-Trejo Juan Antonio , Bobadilla Norma A.
Published: May 2023

Acute kidney injury (AKI) is a global health problem and has recently been recognized as a risk factor for developing chronic kidney disease (CKD). Unfortunately, there are no effective treatments to reduce or prevent AKI, which results in high morbidity and mortality rates. Ischemic preconditioning (IPC) has emerged as a promising strategy to prevent, to the extent possible, renal tissue from AKI. Several studies have used this strategy, which involves short or long cycles of ischemia/reperfusion (IR) prior to a potential fatal ischemic injury. In most of these studies, IPC was effective at reducing renal damage. Since the first study that showed renoprotection due to IPC, several studies have focused on finding the best strategy to activate correctly and efficiently reparative mechanisms, generating different modalities with promising results. In addition, the studies performing remote IPC, by inducing an ischemic process in distant tissues before a renal IR, are also addressed. Here, we review in detail existing studies on IPC strategies for AKI pathophysiology and the proposed triggering mechanisms that have a positive impact on renal function and structure in animal models of AKI and in humans, as well as the prospects and challenges for its clinical application.
Structure and Function of Membrane Proteins
Authors: Fliegel Larry
Published: May 2023

While we have a great deal of information on the human genome, in many cases we still know little about the structure’s function, the regulation of membrane proteins and how they are altered in health and disease [...]
Special Issue “Role of Redox Homeostasis and Oxidative Stress in Human Health”
Authors: Ho Hung-Yao
Published: May 2023

Redox homeostasis plays essential roles in the regulation of the physiological process [...]
Upside-Down Preference in the Forskolin-Induced In Vitro Differentiation of 50B11 Sensory Neurons: A Morphological Investigation by Label-Free Non-Linear Microscopy
Authors: Zupin Luisa , Psilodimitrakopoulos Sotiris , Celsi Fulvio , Papadimitriou Lina , Ranella Anthi , Crovella Sergio , Ricci Giuseppe , Stratakis Emmanuel , Pascolo Lorella
Published: May 2023

In this study, we revealed a peculiar morphological feature of 50B11 nociceptive sensory neurons in in vitro culture related to the forskolin-induced differentiation of these cells growing upside-down on cover glass supports. Multi-photon non-linear microscopy was applied to monitor increased neurite arborization and elongation. Under live and unstained conditions, second harmonic generation (SHG) microscopy could monitor microtubule organization inside the cells while also correlating with the detection of cellular multi-photon autofluorescence, probably derived from mitochondria metabolites. Although the differentiated cells of each compartment did not differ significantly in tubulin or multi-photon autofluorescence contents, the upturned neurons were more elongated, presenting a higher length/width cellular ratio and longer neurites, indicative of differentiated cells. SHG originating from the axons’ microtubules represented a proper tool to study neurons’ inverted culture in live conditions without exogenous staining. This work represents the first instance of examining neuronal cell lines growing and differentiated in an upside-down orientation, allowing a possible improvement of 50B11 as a model in physiology studies of sensory neurons in peripheric nervous system disease (e.g., Fabry disease, Friedreich ataxia, Charcot–Marie–Tooth, porphyria, type 1 diabetes, Guillain–Barré syndrome in children) and analgesic drug screening.
Studies on Chemical Composition, Structure and Potential Applications of Keratoisis Corals
Authors: Gorzelak Mieczysław , Nowak Dorota , Kuczumow Andrzej , Tracey Dianne M. , Adamowski Witold , Nowak Jakub , Kosiński Jakub , Gągała Jacek , Blicharski Tomasz , Lasota Agnieszka , Jabłoński Mirosław , Pawlicz Jarosław , Jarzębski Maciej
Published: May 2023

The chemical composition and structure of bamboo octocoral Keratoisis spp. skeletons were investigated by using: Scanning Electron Microscopy SEM, Raman Microscopy, X-ray Diffraction XRD, Laser Ablation–Inductively Coupled Plasma LA-ICP, and amino acid analyzers. Elements discovered in the nodes (mainly organic parts of the skeleton) of bamboo corals showed a very interesting arrangement in the growth ring areas, most probably enabling the application of bamboo corals as palaeochronometers and palaeothermometers. LA-ICP results showed that these gorgonian corals had an unusually large content of bromine, larger than any other organism yet studied. The local concentration of bromine in the organic part of the growth rings of one of the studied corals grew up to 29,000 ppm of bromine. That is over 440 times more than is contained in marine water and 35 times more than Murex contains, the species which was used to make Tyrian purple in ancient times. The organic matter of corals is called gorgonin, the specific substance that both from the XRD and Raman studies seem to be very similar to the reptile and bird keratins and less similar to the mammalian keratins. The missing cross-linking by S-S bridges, absence of aromatic rings, and significant participation of β-turn organization of peptides differs gorgonin from keratins. Perhaps, the gorgonin belongs to the affined but still different substances concerning reptile and bird keratin and in relation to the more advanced version—the mammalian one. Chemical components of bamboo corals seem to have great medical potential, with the internodes as material substituting the hard tissues and the nodes as the components of medicines.
Towards Protection of Nucleic Acids from Herbicide Attack: Self-Assembly of Betaines Based on Pillar[5]arene with Glyphosate and DNA
Authors: Nazarova Anastasia , Padnya Pavel , Khannanov Arthur , Khabibrakhmanova Aleksandra , Zelenikhin Pavel , Stoikov Ivan
Published: May 2023

Herbicides are one of the main parts of pesticides used today. Due to the high efficiency and widespread use of glyphosate-based herbicides, the search for substances reducing their genotoxicity is an important interdisciplinary task. One possible approach for solving the problem of herbicide toxicity is to use compounds that can protect DNA from damage by glyphosate derivatives. For the first time, a method for developing DNA-protecting measures against glyphosate isopropylamine salt (GIS) damage was presented and realized, based on low-toxicity water-soluble pillar[5]arene derivatives. Two- and three-component systems based on pillar[5]arene derivatives, GIS, and model DNA from salmon sperm, as well as their cytotoxicity, were studied. The synthesized pillar[5]arene derivatives do not interact with GIS, while GIS is able to bind DNA from salmon sperm with lgKa = 4.92. The pillar[5]arene betaine derivative containing fragments of L-phenylalanine and the ester derivative with diglycine fragments bind DNA with lgKa = 5.24 and lgKa = 4.88, respectively. The study of the associates (pillar[5]arene-DNA) with GIS showed that the interaction of GIS with DNA is inhibited only by the betaine pillar[5]arene containing fragments of L-Phe (lgKa = 3.60). This study has shown a possible application of betaine pillar[5]arene derivatives for nucleic acid protection according to its competitive binding with biomacromolecules.
Investigating Chemokine-Matrix Networks in Breast Cancer: Tenascin-C Sets the Tone for CCL2
Authors: Gschwandtner Martha , Gammage Anís N. , Deligne Claire , Mies Linda F. M. , Domaingo Alissa , Murdamoothoo Devardarssen , Loustau Thomas , Schwenzer Anja , Derler Rupert , Carapito Raphael , Koch Manuel , Mörgelin Matthias , Orend Gertraud , Kungl Andreas J. , Midwood Kim S.
Published: May 2023

Bidirectional dialogue between cellular and non-cellular components of the tumor microenvironment (TME) drives cancer survival. In the extracellular space, combinations of matrix molecules and soluble mediators provide external cues that dictate the behavior of TME resident cells. Often studied in isolation, integrated cues from complex tissue microenvironments likely function more cohesively. Here, we study the interplay between the matrix molecule tenascin-C (TNC) and chemokine CCL2, both elevated in and associated with the progression of breast cancer and playing key roles in myeloid immune responses. We uncover a correlation between TNC/CCL2 tissue levels in HER2+ breast cancer and examine the physical and functional interactions of these molecules in a murine disease model with tunable TNC levels and in in vitro cellular and cell-free models. TNC supported sustained CCL2 synthesis, with chemokine binding to TNC via two distinct domains. TNC dominated the behavior of tumor-resident myeloid cells; CCL2 did not impact macrophage survival/activation whilst TNC facilitated an immune suppressive macrophage phenotype that was not dependent on or altered by CCL2 co-expression. Together, these data map new binding partners within the TME and demonstrate that whilst the matrix exerts transcriptional control over the chemokine, each plays a distinct role in subverting anti-tumoral immunity.
In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
Authors: Zhang Lei , Zhang Hongtao , Du Shiqi , Song Xingju , Hu Dandan
Published: May 2023

Intestinal coccidiosis is a common parasitic disease in livestock, caused by the infection of Eimeria and Cystoisospora parasites, which results in great economic losses to animal husbandry. Triazine compounds, such as toltrazuril and diclazuril, are widely used in the treatment and chemoprophylaxis of coccidiosis. Unfortunately, widespread drug resistance has compromised their effectiveness. Most studies have focused on prophylaxis and therapeutics with toltrazuril in flocks, while a comprehensive understanding of how toltrazuril treatment alters the transcriptome of E. tenella remains unknown. In this study, merozoites of E. tenella were treated in vitro with 0.5 μg/mL toltrazuril for 0, 1, 2 and 4 h, respectively. The gene transcription profiles were then compared by high-throughput sequencing. Our results showed that protein hydrolysis genes were significantly upregulated after drug treatment, while cell cycle-related genes were significantly downregulated, suggesting that toltrazuril may affect parasite division. The expression of redox-related genes was upregulated and elevated levels of ROS and autophagosomes were detected in the parasite after toltrazuril treatment, suggesting that toltrazuril may cause oxidative stress to parasite cells and lead to its autophagy. Our results provide basic knowledge of the response of Eimeria genes to toltrazuril and further analysis of the identified transcriptional changes can provide useful information for a better understanding of the mechanism of action of toltrazuril against Eimeria.
Mechanism Exploration of Amyloid-β-42 Disaggregation by Single-Chain Variable Fragments of Alzheimer’s Disease Therapeutic Antibodies
Authors: Fan Xing , Xu Lipeng , Zhang Jianhao , Wang Yidan , Wu Zirui , Sun Wenjing , Yao Xin , Wang Xu , Guan Shanshan , Shan Yaming
Published: May 2023

Alzheimer’s disease (AD) is a specific neurodegenerative disease. This study adopts single-chain variable fragments (scFvs) as a potential immunotherapeutic precursor for AD. According to the remarkable effects of monoclonal antibodies, such as the depolymerization or promotion of Aβ42 efflux by Crenezumab, Solanezumab, and 12B4, it is attractive to prepare corresponding scFvs targeting amyloid-β-42 protein (Aβ42) and investigate their biological activities. Crenezumab-like scFv (scFv-C), Solanezumab-like scFv (scFv-S), and 12B4-like scFv (scFv-12B4) were designed and constructed. The thermal stabilities and binding ability to Aβ42 of scFv-C, scFv-S, and scFv-12B4 were evaluated using unfolding profile and enzyme-linked immunosorbent assay. As the results indicated that scFv-C could recognize Aβ42 monomer/oligomer and promote the disaggregation of Aβ42 fiber as determined by the Thioflavin-T assay, the potential mechanism of its interaction with Aβ42 was investigated using molecular dynamics analysis. Interactions involving hydrogen bonds and salt bonds were predicted between scFv-C and Aβ42 pentamer, suggesting the possibility of inhibiting further aggregation of Aβ42. The successfully prepared scFvs, especially scFv-C, with favorable biological activity targeting Aβ42, might be developed for a potentially efficacious clinical application for AD.
Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures
Authors: Kopaeva Marina Yu. , Azieva Asya M. , Cherepov Anton B. , Zarayskaya Irina Yu.
Published: May 2023

Lactoferrin (Lf) is a multifunctional protein from the transferrin family. Of particular interest is the ability of Lf to affect a wide range of neuronal processes by modulating the expression of genes involved in long-term neuroplasticity. The expression of the immediate early gene c-fos that is rapidly activated in response to external influences, and its product, transcription factor c-Fos, is widely used as a marker of long-term neuronal plasticity. The present study aims to examine the effect of human Lf on the induction of transcription factor c-Fos in the primary mouse neuronal cultures after stimulation and to determine the cellular localization of human Lf and its colocalization with induced c-Fos protein. Primary dissociated cultures of hippocampal cells were obtained from the brains of newborn C57BL/6 mice (P0-P1). On day 7 of culturing, human Lf was added to the medium. After 24 h (day 8 in culture), c-Fos protein was induced in cells by triple application of 50 mM KCl. c-Fos content was analyzed using the immunofluorescent method 2 h after stimulation. Stimulation promoted exogenous Lf translocation into the nuclei of cultured neuronal cells, which correlated with increased induction of transcription factor c-Fos and was accompanied by nuclear colocalization of these proteins. These results attest to the potential of Lf as a modulator of neuronal processes and open up new prospects in studying the mechanisms of the regulatory effects of lactoferrin on cell function.
Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction
Authors: Xu Yichen , Zheng Huabo , Nilcham Pakhwan , Bucur Octavian , Vogt Felix , Slabu Ioana , Liehn Elisa Anamaria , Rusu Mihaela
Published: May 2023

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.
Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme
Authors: Su Hongfei , Chen Xiaolin , Chen Shijing , Guo Mingzhang , Liu Huilin
Published: May 2023

Heme has a variety of functions, from electronic reactions to binding gases, which makes it useful in medical treatments, dietary supplements, and food processing. In recent years, whole-cell system-based heme biosynthesis methods have been continuously explored and optimized as an alternative to the low-yield, lasting, and adverse ecological environment of chemical synthesis methods. This method relies on two biosynthetic pathways of microbial precursor 5-aminolevulinic acid (C4, C5) and three known downstream biosynthetic pathways of heme. This paper reviews the genetic and metabolic engineering strategies for heme production in recent years by optimizing culture conditions and techniques from different microorganisms. Specifically, we summarized and analyzed the possibility of using biosensors to explore new strategies for the biosynthesis of heme from the perspective of synthetic biology, providing a new direction for future exploration.
B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma
Authors: Mohammadnezhad Leila , Shekarkar Azgomi Mojtaba , La Manna Marco Pio , Guggino Giuliana , Botta Cirino , Dieli Francesco , Caccamo Nadia
Published: May 2023

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells’ signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells’ signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma.
Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells
Authors: Varzideh Fahimeh , Gambardella Jessica , Kansakar Urna , Jankauskas Stanislovas S. , Santulli Gaetano
Published: May 2023

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. ESCs have two distinctive properties: ability to proliferate indefinitely, a feature referred as “self-renewal”, and to differentiate into different cell types, a peculiar characteristic known as “pluripotency”. Self-renewal and pluripotency of ESCs are finely orchestrated by precise external and internal networks including epigenetic modifications, transcription factors, signaling pathways, and histone modifications. In this systematic review, we examine the main molecular mechanisms that sustain self-renewal and pluripotency in both murine and human ESCs. Moreover, we discuss the latest literature on human naïve pluripotency.
Clinical and Translational Applications of Serological and Histopathological Biomarkers in Metastatic Breast Cancer: A Comprehensive Review
Authors: Pekarek Leonel , Sánchez Cendra Alicia , Roberts Cervantes Eduardo D. , Sánchez Cendra Cristina , Fraile-Martinez Oscar , García-Montero Cielo , Diaz-Pedrero Raul , Torres-Carranza Diego , Lopez-Gonzalez Laura , Aguado-Henche Soledad , Rios-Parra Antonio , García-Puente Luis M. , García-Honduvilla Natalio , Bujan Julia , Alvarez-Mon Melchor , Saez Miguel A. , Ortega Miguel A.
Published: May 2023

Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.
Changes in Structural and Thermodynamic Properties of Starch during Potato Tuber Dormancy
Authors: Wasserman Lyubov A. , Kolachevskaya Oksana O. , Krivandin Alexey V. , Filatova Anna G. , Gradov Oleg V. , Plashchina Irina G. , Romanov Georgy A.
Published: May 2023

The main reserve polysaccharide of plants—starch—is undoubtedly important for humans. One of the main sources of starch is the potato tuber, which is able to preserve starch for a long time during the so-called dormancy period. However, accumulated data show that this dormancy is only relative, which raises the question of the possibility of some kind of starch restructuring during dormancy periods. Here, the effect of long-term periods of tuber rest (at 2–4 °C) on main parameters of starches of potato tubers grown in vivo or in vitro were studied. Along with non-transgenic potatoes, Arabidopsis phytochrome B (AtPHYB) transformants were investigated. Distinct changes in starch micro and macro structures—an increase in proportion of amorphous lamellae and of large-sized and irregular-shaped granules, as well as shifts in thickness of the crystalline lamellae—were detected. The degree of such alterations, more pronounced in AtPHYB-transgenic tubers, increased with the longevity of tuber dormancy. By contrast, the polymorphic crystalline structure (B-type) of starch remained unchanged regardless of dormancy duration. Collectively, our data support the hypothesis that potato starch remains metabolically and structurally labile during the entire tuber life including the dormancy period. The revealed starch remodeling may be considered a process of tuber preadaptation to the upcoming sprouting stage.
Porous Zirconia Scaffolds Functionalized with Calcium Phosphate Layers and PLGA Nanoparticles Loaded with Hydrophobic Gentamicin
Authors: Pudełko Iwona , Moskwik Anna , Kwiecień Konrad , Kriegseis Sven , Krok-Borkowicz Małgorzata , Schickle Karolina , Ochońska Dorota , Dobrzyński Piotr , Brzychczy-Włoch Monika , Gonzalez-Julian Jesus , Pamuła Elżbieta
Published: May 2023

Implant-related infections are a worldwide issue that is considered very challenging. Conventional therapies commonly end up failing; thus, new solutions are being investigated to overcome this problem. The in situ delivery of the drug at the implant site appears to be more sufficient compared to systemic antibiotic therapy. In this study, we manufactured porous zirconia scaffolds using the foam replication method. To improve their overall bioactivity, they were coated with a calcium phosphate (CaP) layer containing antibiotic-loaded degradable polymer nanoparticles (NPs) obtained by the double emulsion method to achieve the antibacterial effect additionally. Encapsulation efficiency (EE) and drug loading (DL) were superior and were equal to 99.9 ± 0.1% and 9.1 ± 0.1%, respectively. Scaffolds were analyzed with scanning electron microscopy, and their porosity was evaluated. The porosity of investigated samples was over 90% and resembled the microstructure of spongy bone. Furthermore, we investigated the cytocompatibility with osteoblast-like MG-63 cells and antimicrobial properties with Staphylococcus aureus. Scaffolds coated with a CaP layer were found non-toxic for MG-63 cells. Moreover, the presence of antibiotic-loaded nanoparticles had no significant influence on cell viability, and the obtained scaffolds inhibited bacteria growth. Provided processes of fabrication of highly porous zirconia scaffolds and surface functionalization allow minimizing the risk of implant-related infection.
Gender-Specific Differences in Serum Sphingomyelin Species in Patients with Hepatitis C Virus Infection—Sphingomyelin Species Are Related to the Model of End-Stage Liver Disease (MELD) Score in Male Patients
Authors: Peschel Georg , Weigand Kilian , Grimm Jonathan , Müller Martina , Krautbauer Sabrina , Höring Marcus , Liebisch Gerhard , Buechler Christa
Published: May 2023

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients.
Alpha-Deoxyguanosine to Reshape the Alpha-Thrombin Binding Aptamer
Authors: Kolganova Natalia A. , Tsvetkov Vladimir B. , Stomakhin Andrey A. , Surzhikov Sergei A. , Timofeev Edward N. , Varizhuk Irina V.
Published: May 2023

Modification of DNA aptamers is aimed at increasing their thermodynamic stability, and improving affinity and resistance to biodegradation. G-quadruplex DNA aptamers are a family of affinity ligands that form non-canonical DNA assemblies based on a G-tetrads stack. Modification of the quadruplex core is challenging since it can cause complete loss of affinity of the aptamer. On the other hand, increased thermodynamic stability could be a worthy reward. In the current paper, we developed new three- and four-layer modified analogues of the thrombin binding aptamer with high thermal stability, which retain anticoagulant activity against alpha-thrombin. In the modified aptamers, one or two G-tetrads contained non-natural anti-preferred alpha-deoxyguanosines at specific positions. The use of this nucleotide analogue made it possible to control the topology of the modified structures. Due to the presence of non-natural tetrads, we observed some decrease in the anticoagulant activity of the modified aptamers compared to the natural prototype. This negative effect was completely compensated by conjugation of the aptamers with optimized tripeptide sequences.
A Novel Anti-CD44 Variant 3 Monoclonal Antibody C44Mab-6 Was Established for Multiple Applications
Authors: Suzuki Hiroyuki , Kitamura Kaishi , Goto Nohara , Ishikawa Kenichiro , Ouchida Tsunenori , Tanaka Tomohiro , Kaneko Mika K. , Kato Yukinari
Published: May 2023

Cluster of differentiation 44 (CD44) promotes tumor progression through the recruitment of growth factors and the acquisition of stemness, invasiveness, and drug resistance. CD44 has multiple isoforms including CD44 standard (CD44s) and CD44 variants (CD44v), which have common and unique functions in tumor development. Therefore, elucidating the function of each CD44 isoform in a tumor is essential for the establishment of CD44-targeting tumor therapy. We have established various anti-CD44s and anti-CD44v monoclonal antibodies (mAbs) through the immunization of CD44v3–10-overexpressed cells. In this study, we established C44Mab-6 (IgG1, kappa), which recognized the CD44 variant 3-encoded region (CD44v3), as determined via an enzyme-linked immunosorbent assay. C44Mab-6 reacted with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells (CHO/CD44v3–10) or some cancer cell lines (COLO205 and HSC-3) via flow cytometry. The apparent KD of C44Mab-6 for CHO/CD44v3–10, COLO205, and HSC-3 was 1.5 × 10−9 M, 6.3 × 10−9 M, and 1.9 × 10−9 M, respectively. C44Mab-6 could detect the CD44v3–10 in Western blotting and stained the formalin-fixed paraffin-embedded tumor sections in immunohistochemistry. These results indicate that C44Mab-6 is useful for detecting CD44v3 in various experiments and is expected for the application of tumor diagnosis and therapy.
Geometry and UV-Vis Spectra of Au3+ Complexes with Hydrazones Derived from Pyridoxal 5′-Phosphate: A DFT Study
Authors: Pimenov Oleg A. , Grazhdan Konstantin V. , Zavalishin Maksim N. , Gamov George A.
Published: May 2023

Gold(III) complexes with different ligands can provide researchers with a measure against pathogenic microorganisms with antibiotic resistance. We reported in our previous paper that the UV-Vis spectra of different protonated species of complexes formed by gold(III) and five hydrazones derived from pyridoxal 5′-phosphate are similar to each other and to the spectra of free protonated hydrazones. The present paper focuses on the reasons of the noted similarity in electron absorption spectra. The geometry of different protonated species of complexes of gold(III) and hydrazones (15 structures in total) was optimized using the density functional theory (DFT). The coordination polyhedron of gold(III) bond critical points were further studied to identify the symmetry of the gold coordination sphere and the type of interactions that hold the complex together. The UV-Vis spectra were calculated using TD DFT methods. The molecular orbitals were analyzed to interpret the calculated spectra.
Single-Cell Analysis in Immuno-Oncology
Authors: Christodoulou Maria-Ioanna , Zaravinos Apostolos
Published: May 2023

The complexity of the cellular and non-cellular milieu surrounding human tumors plays a decisive role in the course and outcome of disease. The high variability in the distribution of the immune and non-immune compartments within the tumor microenvironments (TME) among different patients governs the mode of their response or resistance to current immunotherapeutic approaches. Through deciphering this diversity, one can tailor patients’ management to meet an individual’s needs. Single-cell (sc) omics technologies have given a great boost towards this direction. This review gathers recent data about how multi-omics profiling, including the utilization of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (scATAC-seq), T-cell receptor sequencing (scTCR-seq), mass, tissue-based, or microfluidics cytometry, and related bioinformatics tools, contributes to the high-throughput assessment of a large number of analytes at single-cell resolution. Unravelling the exact TCR clonotype of the infiltrating T cells or pinpointing the classical or novel immune checkpoints across various cell subsets of the TME provide a boost to our comprehension of adaptive immune responses, their antigen specificity and dynamics, and grant suggestions for possible therapeutic targets. Future steps are expected to merge high-dimensional data with tissue localization data, which can serve the investigation of novel multi-modal biomarkers for the selection and/or monitoring of the optimal treatment from the current anti-cancer immunotherapeutic armamentarium.
U-Net-Based CNN Architecture for Road Crack Segmentation
Authors: Di Benedetto Alessandro , Fiani Margherita , Gujski Lucas Matias
Published: May 2023

Many studies on the semantic segmentation of cracks using the machine learning (ML) technique can be found in the relevant literature. To date, the results obtained are quite good, but often the accuracy of the trained model and the results obtained are evaluated using traditional metrics only, and in most cases, the goal is to detect only the occurrence of cracks. Particular attention should be paid to the thickness of the segmented crack since, in road pavement maintenance, the width of the crack is the main parameter and is the one that characterizes the severity levels. The aim of our study is to optimize the crack segmentation process through the implementation of a modified U-Net model-based algorithm. For this, the Crack500 dataset is used, and then the results are compared with those obtained from the U-Net algorithm, which is currently found to be the most accurate and performant in the literature. The results are promising and accurate, as the findings on the shape and width of the segmented cracks are very close to reality.
Theoretical Insight on the Formation Mechanism of a Trisubstituted Derivative of Closo-Decaborate Anion [B10H7O2CCH3(NCCH3)]0
Authors: Klyukin Ilya N. , Kolbunova Anastasia V. , Novikov Alexander S. , Zhdanov Andrey P. , Zhizhin Konstantin Yu. , Kuznetsov Nikolay T.
Published: May 2023

A theoretical modelling of the interaction process between a protonated complex of carboxonium derivative [2,6-B10H8O2CCH3*Hfac]0 and acetonitrile molecule CH3CN was carried out. As a result of the process, a trisubstituted [B10H7O2CCH3(NCCH3)]0 derivative was formed. This reaction has an electrophile-induced nucleophilic substitution (EINS) mechanism. The main intermediates and transition states of the substitution process were established. As in the case of all previously investigated EINS processes, the key intermediate was an anion with a dihydrogen H2 fragment attached to one boron atom (B(H2) structure motif). The process of nucleophilic substitution can proceed on a different position of the cluster cage. The main potential pathways were assessed. It was established that substitution on the B4 position of the cluster cage was the most energetically favourable, and the [2,4,6-B10H7O2CCH3(NCCH3)]0 isomer was formed.
Sport-Related Effect on Knee Strength Profile during Puberty: Basketball vs. Soccer
Authors: Gerodimos Vassilis , Karatrantou Konstantina , Batatolis Christos , Ioakimidis Panagiotis
Published: May 2023

The present study examined and compared the isokinetic peak torque and the reciprocal ratios of the knee joint between young basketball and soccer players. An amount of 100 soccer and 100 basketball players took part in this study and were separated into five equal groups (n = 20), according to their chronological age (12, 13, 14, 15, and 16 years old). The absolute concentric (CON) and eccentric (ECC) peak torque of the knee flexor and extensor muscles (at 60°/s, 180°/s) were assessed using a Cybex Norm dynamometer, and the relative peak torque (per unit of body mass), as well as the conventional (CON/CON; ECC/ECC) and functional (CON/ECC; ECC/CON) ratios, were calculated. Data analysis indicated that the basketball players had higher absolute peak torque values than the soccer players throughout their developmental ages (p < 0.05). When the isokinetic peak torque values were normalized relative to body mass, no differences were observed between basketball and soccer players in any age group (p > 0.05). Additionally, no differences were observed in conventional and functional ratios between soccer and basketball players (p > 0.05). In conclusion, it appears that, during developmental ages (12–16 years old), the isokinetic strength profile (independent of body mass affecting absolute values) of knee extensor and flexor muscles develops similarly in basketball and soccer players.
A Time-Mode PWM 1st Order Low-Pass Filter
Authors: Pagkalos Konstantinos P. , Panetas-Felouris Orfeas , Vlassis Spyridon
Published: May 2023

In this work, a first-order low-pass filter is proposed as suitable for time-mode PWM signal processing. In time-mode PWM signal processing, the pulse width of a rectangular pulse is the processing variable. The filter is constructed using basic time-mode building blocks such as time registers and time adders and so it is characterized by low complexity which can lead to the modular and versatile design of higher-order filters. All the building blocks of the filter were designed and verified in a TSMC 65 nm technology process. The sampling frequency was 5 MHz, the gain of the filter at low frequencies was at −0.016 dB, the cut-off frequency was 1.2323 MHz, and the power consumption was around 59.1 μW.
Numerical and Experimental Investigations on Tube Section Flattening for Parameter Identification and Advanced Material Modeling of Tubes
Authors: Reuther Franz , Winter Sven , Fritsch Sebastian , Kräusel Verena , Wagner Martin F.-X. , Psyk Verena
Published: May 2023

At present, there are no experimental methods that allow for the complete direction-dependent mechanical characterization of tubes. This considerably limits the parameterization of complex, anisotropic material models. The present study introduces a new approach to overcome these limitations: tube sections are first flattened into a planar geometry; then, samples for uniaxial testing are taken out of the flattened tube section and used for parameter identification. In this paper, special emphasis is placed on the intermediate step of flattening, which is investigated in detail both numerically and experimentally. Flattening by pressing is identified as the most advantageous of several options, and the procedure is optimized by numerical simulations that address springback compensation. Experimental validation is performed on tubes (steel E235) with a diameter of 60 mm and an average wall thickness of 1.524 mm. Tube sections are successfully flattened in a custom-built tool with only small remaining out-of-plane displacements after flattening. The numerically predicted pressing force curves agree very well with the experimental data.
Model and Simulation of a Floating Hybrid Wind and Current Turbines Integrated Generator System, Part II: Hydrodynamics and Acting Forces
Authors: Tamarit Fernando , García Emilio , Quiles Eduardo , Correcher Antonio
Published: May 2023

This work is part of a series of publications that propose a floating hybrid system for which a simulation tool has been developed, called FHYGSYS (Floating Hybrid Generator Systems Simulator). The objective of this series of publications is to analyze the behavior and to evaluate different control strategies of the floating hybrid system. This system consists of an “OC3-Hywind” wind turbine and two marine current turbines presented by the authors in previous publications. This work completes the exposition of the mathematical model of the floating hybrid system started in a previous publication (Part I), in which the inertial, kinematic, and dynamic parts of the model were described. In this second part, the forces acting on the floating system are extensively described, and the turbines are modeled using the so-called One-Dimensional theory (or also known as Simple theory). The results obtained with the FHYGSYS simulation tool have been validated—through a code-to-code comparison—with FASTv8, both in the first part and in this second part of this work.
Small-Scale Model Experiments on Plastic Fragment Removal from Water Flows Using Multiple Filters in a Floating Body
Authors: Islam Reyana , Nishi Yoshiki
Published: May 2023

Increasing plastic fragments (PFs) in the environment have attracted considerable social and academic attention. Several methods have been proposed to mitigate plastic pollution, such as filtration and degradation. This study focuses on the removal of plastic fragments from a water flow. A field collection survey of beached PFs was conducted at Kurihama Beach (Yokosuka, Kanagawa, Japan) to identify their polymer types and quantify different PFs. An anchored-buoy-type filter was designed to capture surface and submerged PFs from the water flow. A small-scale experimental apparatus was developed with the incorporation of these filters. Four types of filters (steel wire frame, plankton net, reverse osmosis filter, and carbon-block filter) were used as PF removers based on their size. The PF capture experiment was conducted at various PF concentrations, water densities, and flow speeds. The number of captured PFs was calculated using particle counting and mass measurement. The average efficiency of the designed filter was 81.53%, with the efficiency reaching 94.5%. The designed filter was reported to work well in both seawater and freshwater.
Circadian Fluctuation Changes in Intraocular Pressure Measured Using a Contact Lens Sensor in Patients with Glaucoma after the Adjunctive Administration of Ripasudil: A Prospective Study
Authors: Huang Shih-Kung , Ishii Mai , Mizuki Yuki , Kawagoe Tatukata , Takeuchi Masaki , Nomura Eiichi , Mizuki Nobuhisa
Published: May 2023

Nocturnal and circadian intraocular pressure (IOP) fluctuations are important issues in glaucoma treatment. Ripasudil 0.4% eye drops, a new glaucoma medication, lowers IOP by increasing aqueous humor outflow through the trabecular meshwork. We aimed to compare differences between circadian IOP fluctuations measured using a contact lens sensor (CLS) before and after administering 0.4% ripasudil eye drops adjunctively to patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Patients with POAG (n = 1) and NTG (n = 5) underwent 24 h IOP monitoring with a CLS before and after administering ripasudil eye drops every 12 h (8 a.m., 8 p.m.) for 2 weeks without discontinuing currently used glaucoma medications. No vision-threatening adverse event occurred. The reduction in IOP fluctuation and the reduction in the SD of IOP in 24 h, awake time and sleep time did not reach statistical significance. The baseline office-hour IOP, which was measured using Goldmann applanation tonometry (GAT), ranged in the low teens, and the reduction in office-hour IOP also did not show a significant difference. Further study is necessary to evaluate whether the low baseline IOP with less IOP reduction relates to attenuated IOP fluctuation reduction.
Static and Dynamic Mechanical Behaviour of Hybrid-PBF-LB/M-Built and Hot Isostatic Pressed Lattice Structures
Authors: Sommer David , Esen Cemal , Hellmann Ralf
Published: May 2023

We report on a comprehensive study of the mechanical properties of maraging steel body-centred cubic lattice structures fabricated by a hybrid additive manufacturing technology that combines laser powder bed fusion with in situ high-speed milling. As the mechanical properties of additive manufactured components are inferior to, e.g., cast components, surface modifications can improve the mechanical behaviour. Different hybrid additive manufacturing technologies have been designed using additive and subtractive processes, improving process quality. Following this, mechanical testing is performed with respect to static tensile properties and dynamic stress, hardness, and porosity, comparing specimens manufactured by laser powder bed fusion only to those manufactured by the hybrid approach. In addition, the influence of different heat-treatment techniques on the mechanical behaviour of the lattice structures is investigated, namely solution and aging treatment as well as hot isostatic pressing. Thus, the influence of the superior surface quality due to the hybrid approach is evaluated, leading to, e.g., an offset of about 14–16% for the static testing of HIP lattice structures. Furthermore, the dynamic load behaviour can be improved with a finished surface, heading to a shift of the different zones of fatigue behaviour in the testing of hybrid-built specimens.
Two-Level Scheme for Identification of the Relaxation Time Spectrum Using Stress Relaxation Test Data with the Optimal Choice of the Time-Scale Factor
Authors: Stankiewicz Anna
Published: May 2023

The viscoelastic relaxation spectrum is vital for constitutive models and for insight into the mechanical properties of materials, since, from the relaxation spectrum, other material functions used to describe rheological properties can be uniquely determined. The spectrum is not directly accessible via measurement and must be recovered from relaxation stress or oscillatory shear data. This paper deals with the problem of the recovery of the relaxation time spectrum of linear viscoelastic material from discrete-time noise-corrupted measurements of a relaxation modulus obtained in the stress relaxation test. A two-level identification scheme is proposed. In the lower level, the regularized least-square identification combined with generalized cross-validation is used to find the optimal model with an arbitrary time-scale factor. Next, in the upper level, the optimal time-scale factor is determined to provide the best fit of the relaxation modulus to experiment data. The relaxation time spectrum is approximated by a finite series of power–exponential basis functions. The related model of the relaxation modulus is proved to be given by compact analytical formulas as the products of power of time and the modified Bessel functions of the second kind. The proposed approach merges the technique of an expansion of a function into a series of independent basis functions with the least-squares regularized identification and the optimal choice of the time-scale factor. Optimality conditions, approximation error, convergence, noise robustness and model smoothness are studied analytically. Applicability ranges are numerically examined. These studies have proved that using a developed model and algorithm, it is possible to determine the relaxation spectrum model for a wide class of viscoelastic materials. The model is smoothed and noise robust; small model errors are obtained for the optimal time-scale factors. The complete scheme of the hierarchical computations is outlined, which can be easily implemented in available computing environments.