bluuebunny/crossref_metadata_2025 huggingface dataset:
LH/hCG Regulation of Circular RNA in Mural Granulosa Cells during the Periovulatory Period in Mice
Authors: Chakravarthi V. Praveen , Hung Wei-Ting , Yellapu Nanda Kumar , Gunewardena Sumedha , Christenson Lane K.
Published: August 2023

Ovarian follicles undergo a series of dynamic changes following the ovulatory surge of luteinizing hormone including cumulus expansion, oocyte maturation, ovulation, and luteinization. Post-transcriptional gene regulatory events are critical for mediating LH follicular responses, and among all RNA isoforms, circular RNA (circRNA) is one of the most abundant forms present in cells, yet they remain the least studied. Functionally, circRNA can act as miRNA sponges, protein sponges/decoys, and regulators of transcription and translation. In the context of ovarian follicular development, the identity and roles of circRNA are relatively unknown. In the present study, high throughput RNA sequencing of granulosa cells immediately prior to and 4-h after the LH/hCG surge identified 42,381 circRNA originating from 7712 genes. A total of 54 circRNA were identified as differentially expressed between 0-h and 4-h time points (Fold Change ± 1.5, FDR ≤ 0.1), among them 42 circRNA were upregulated and 12 circRNA were downregulated. All differentially expressed circRNA between the 0-h and 4-h groups were subjected to circinteractome analysis and identified networks of circRNA-protein and circRNA-miRNA were further subjected to “micro-RNA target filter analysis” in Ingenuity Pathway Analyses, which resulted in the identification of miRNA targeted mRNAs. A comparison of these circRNA target mRNAs with LH-induced mRNAs identified Runx2, Egfr, Areg, Sult1el, Cyp19a1, Cyp11a1, and Hsd17b1 as targets of circKif2, circVcan, circMast4, and circMIIt10. These newly identified LH/hCG-induced circRNA, their target miRNA and protein networks provide new insights into the complex interactions associated with periovulatory follicular development.
No Time to Relax and Unwind: Exploration of Topoisomerases and a Growing Field of Study
Authors: Deweese Joseph E. , Osheroff Neil
Published: August 2023

With the topoisomerase field in its sixth decade [...]
Targeting Oncogenic Mutant p53 and BCL-2 for Small Cell Lung Cancer Treatment
Authors: Neely Victoria , Manchikalapudi Alekhya , Nguyen Khanh , Dalton Krista , Hu Bin , Koblinski Jennifer E. , Faber Anthony C. , Deb Sumitra , Harada Hisashi
Published: August 2023

Through a unique genomics and drug screening platform with ~800 solid tumor cell lines, we have found a subset of SCLC cell lines are hypersensitive to venetoclax, an FDA-approved inhibitor of BCL-2. SCLC-A (ASCL1 positive) and SCLC-P (POU2F3 positive), which make up almost 80% of SCLC, frequently express high levels of BCL-2. We found that a subset of SCLC-A and SCLC-P showed high BCL-2 expression but were venetoclax-resistant. In addition, most of these SCLC cell lines have TP53 missense mutations, which make a single amino acid change. These mutants not only lose wild-type (WT) p53 tumor suppressor functions, but also acquire novel cancer-promoting activities (oncogenic, gain-of-function). A recent study with oncogenic mutant (Onc)-p53 knock-in mouse models of SCLC suggests gain-of-function activity can attenuate chemotherapeutic efficacy. Based on these observations, we hypothesize that Onc-p53 confers venetoclax resistance and that simultaneous inhibition of BCL-2 and Onc-p53 induces synergistic anticancer activity in a subset of SCLC-A and SCLC-P. We show here that (1) down-regulation of Onc-p53 increases the expression of a BH3-only pro-apoptotic BIM and sensitizes to venetoclax in SCLC-P cells; (2) targeting Onc-p53 by the HSP90 inhibitor, ganetespib, increases BIM expression and sensitizes to venetoclax in SCLC-P and SCLC-A cells. Although there are currently many combination studies for venetoclax proposed, the concept of simultaneous targeting of BCL-2 and Onc-p53 by the combination of venetoclax and HSP90 inhibitors would be a promising approach for SCLC treatment.
EV-miRNA-Mediated Intercellular Communication in the Breast Tumor Microenvironment
Authors: Sepúlveda Francisca , Mayorga-Lobos Cristina , Guzmán Kevin , Durán-Jara Eduardo , Lobos-González Lorena
Published: August 2023

Cancer research has prioritized the study of the tumor microenvironment (TME) as a crucial area of investigation. Understanding the communication between tumor cells and the various cell types within the TME has become a focal point. Bidirectional communication processes between these cells support cellular transformation, as well as the survival, invasion, and metastatic dissemination of tumor cells. Extracellular vesicles are lipid bilayer structures secreted by cells that emerge as important mediators of this cell-to-cell communication. EVs transfer their molecular cargo, including proteins and nucleic acids, and particularly microRNAs, which play critical roles in intercellular communication. Tumor-derived EVs, for example, can promote angiogenesis and enhance endothelial permeability by delivering specific miRNAs. Moreover, adipocytes, a significant component of the breast stroma, exhibit high EV secretory activity, which can then modulate metabolic processes, promoting the growth, proliferation, and migration of tumor cells. Comprehensive studies investigating the involvement of EVs and their miRNA cargo in the TME, as well as their underlying mechanisms driving tumoral capacities, are necessary for a deeper understanding of these complex interactions. Such knowledge holds promise for the development of novel diagnostic and therapeutic strategies in cancer treatment.
Identification and Quantification of the Major Phenolic Constituents in Castanea sativa and Commercial Interspecific Hybrids (C. sativa x C. crenata) Chestnuts Using HPLC–MS/MS
Authors: Medic Aljaz , Kunc Petra , Zamljen Tilen , Hudina Metka , Veberic Robert , Solar Anita
Published: August 2023

Due to the lack of studies on chestnut metabolites, this study was conducted to identify and quantify the major phenolic constituents in chestnuts. Data were compared with the three most commonly grown interspecific hybrids of C. sativa and C. crenata (‘Bouche de Betizac’, ‘Marsol’, and ‘Maraval’) and three “native” accessions of C. sativa. High-performance liquid chromatography coupled with mass spectrometry was used to identify and quantify these compounds. Four dicarboxylic acid derivatives, five hydroxybenzoic acids, nine hydroxycinnamic acids, and three flavanols were identified and quantified, most of them for the first time. Hydroxybenzoic acids were the major phenolic compounds in all chestnut cultivars/accessions, followed by flavanols, dicarboxylic acid derivatives, and hydroxycinnamic acids. Of all the compounds studied, the (epi)catechin dimer was the most abundant in chestnut. The assumption that cultivars from commercial hybrids have a better and different metabolic profile than “native” accessions was refuted.
Multiple Factors Involved in Bone Damage Caused by Chikungunya Virus Infection
Authors: Avila-Trejo Amanda M. , Rodríguez-Páez Lorena I. , Alcántara-Farfán Verónica , Aguilar-Faisal J. Leopoldo
Published: August 2023

Chronic cases of chikungunya fever represent a public health problem in countries where the virus circulates. The disease is prolonged, in some cases, for years, resulting in disabling pain and bone erosion among other bone and joint problems. As time progresses, tissue damage is persistent, although the virus has not been found in blood or joints. The pathogenesis of these conditions has not been fully explained. Additionally, it has been considered that there are multiple factors that might intervene in the viral pathogenesis of the different conditions that develop. Other mechanisms involved in osteoarthritic diseases of non-viral origin could help explain how damage is produced in chronic conditions. The aim of this review is to analyze the molecular and cellular factors that could be involved in the tissue damage generated by different infectious conditions of the chikungunya virus.
Changes in Expression and Function of Placental and Intestinal P-gp and BCRP Transporters during Pregnancy
Authors: Szatmári Péter , Ducza Eszter
Published: August 2023

ABC transporters are ubiquitous in the human body and are responsible for the efflux of drugs. They are present in the placenta, intestine, liver and kidney, which are the major organs that can affect the pharmacokinetic and pharmacologic properties of drugs. P-gp and BCRP transporters are the best-characterized transporters in the ABC superfamily, and they have a pivotal role in the barrier tissues due to their efflux mechanism. Moreover, during pregnancy, drug efflux is even more important because of the developing fetus. Recent studies have shown that placental and intestinal ABC transporters have great importance in drug absorption and distribution. Placental and intestinal P-gp and BCRP show gestational-age-dependent expression changes, which determine the drug concentration both in the mother and the fetus during pregnancy. They may have an impact on the efficacy of antibiotic, antiviral, antihistamine, antiemetic and oral antidiabetic therapies. In this review, we would like to provide an overview of the pharmacokinetically relevant expression alterations of placental and intestinal ABC transporters during pregnancy.
Long-Lasting Epigenetic Changes in the Dopamine Transporter in Adult Animals Exposed to Amphetamine during Embryogenesis: Investigating Behavioral Effects
Authors: Ke Tao , Ambigapathy Ganesh , Ton Thanh , Dhasarathy Archana , Carvelli Lucia
Published: August 2023

The dopamine transporter (DAT) is an integral member of the dopaminergic system and is responsible for the release and reuptake of dopamine from the synaptic space into the dopaminergic neurons. DAT is also the major target of amphetamine (Amph). The effects of Amph on DAT have been intensively studied; however, the mechanisms underlying the long-term effects caused by embryonal exposure to addictive doses of Amph remain largely unexplored. As in mammals, in the nematode C. elegans Amph causes changes in locomotion which are largely mediated by the C. elegans DAT homologue, DAT-1. Here, we show that chronic embryonic exposures to Amph alter the expression of DAT-1 in adult C. elegans via long-lasting epigenetic modifications. These changes are correlated with an enhanced behavioral response to Amph in adult animals. Importantly, pharmacological and genetic intervention directed at preventing the Amph-induced epigenetic modifications occurring during embryogenesis inhibited the long-lasting behavioral effects observed in adult animals. Because many components of the dopaminergic system, as well as epigenetic mechanisms, are highly conserved between C. elegans and mammals, these results could be critical for our understanding of how drugs of abuse initiate predisposition to addiction.
Emerging Roles of Phospholipase C Beta Isozymes as Potential Biomarkers in Cardiac Disorders
Authors: Fazio Antonietta , Evangelisti Camilla , Cappellini Alessandra , Mongiorgi Sara , Koufi Foteini-Dionysia , Neri Irene , Marvi Maria Vittoria , Russo Michele , Ghigo Alessandra , Manzoli Lucia , Fiume Roberta , Ratti Stefano
Published: August 2023

Phospholipase C (PLC) enzymes represent crucial participants in the plasma membrane of mammalian cells, including the cardiac sarcolemmal (SL) membrane of cardiomyocytes. They are responsible for the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) into 1,2-diacylglycerol (DAG) and inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), both essential lipid mediators. These second messengers regulate the intracellular calcium (Ca2+) concentration, which activates signal transduction cascades involved in the regulation of cardiomyocyte activity. Of note, emerging evidence suggests that changes in cardiomyocytes’ phospholipid profiles are associated with an increased occurrence of cardiovascular diseases, but the underlying mechanisms are still poorly understood. This review aims to provide a comprehensive overview of the significant impact of PLC on the cardiovascular system, encompassing both physiological and pathological conditions. Specifically, it focuses on the relevance of PLCβ isoforms as potential cardiac biomarkers, due to their implications for pathological disorders, such as cardiac hypertrophy, diabetic cardiomyopathy, and myocardial ischemia/reperfusion injury. Gaining a deeper understanding of the mechanisms underlying PLCβ activation and regulation is crucial for unraveling the complex signaling networks involved in healthy and diseased myocardium. Ultimately, this knowledge holds significant promise for advancing the development of potential therapeutic strategies that can effectively target and address cardiac disorders by focusing on the PLCβ subfamily.
The Role of Galectin-3 in Heart Failure—The Diagnostic, Prognostic and Therapeutic Potential—Where Do We Stand?
Authors: Zaborska Beata , Sikora-Frąc Małgorzata , Smarż Krzysztof , Pilichowska-Paszkiet Ewa , Budaj Andrzej , Sitkiewicz Dariusz , Sygitowicz Grażyna
Published: August 2023

Heart failure (HF) is a clinical syndrome with high morbidity and mortality, and its prevalence is rapidly increasing. Galectin-3 (Gal-3) is an important factor in the pathophysiology of HF, mainly due to its role in cardiac fibrosis, inflammation, and ventricular remodeling. Fibrosis is a hallmark of cardiac remodeling, HF, and atrial fibrillation development. This review aims to explore the involvement of Gal-3 in HF and its role in the pathogenesis and clinical diagnostic and prognostic significance. We report data on Gal-3 structure and molecular mechanisms of biological function crucial for HF development. Over the last decade, numerous studies have shown an association between echocardiographic and CMR biomarkers in HF and Gal-3 serum concentration. We discuss facts and concerns about Gal-3’s utility in acute and chronic HF with preserved and reduced ejection fraction for diagnosis, prognosis, and risk stratification. Finally, we present attempts to use Gal-3 as a therapeutic target in HF.
Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer
Authors: Levink Iris J. M. , Jansen Maurice P. H. M. , Azmani Zakia , van IJcken Wilfred , van Marion Ronald , Peppelenbosch Maikel P. , Cahen Djuna L. , Fuhler Gwenny M. , Bruno Marco J.
Published: August 2023

Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m2 (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection n = 5, biopsy n = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, p < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 KRAS, 15 TP53, 2 SMAD4, 3 CDKN2A 1 CTNNB1, and 1 PIK3CA), 19 in PJ (3 KRAS, 15 TP53, and 1 SMAD4), and 8 in tissue (2 KRAS, 2 CDKN2A, and 4 TP53). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection.
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain: A Metabolomics Study
Authors: Dias-Carvalho Ana , Margarida-Araújo Ana , Reis-Mendes Ana , Sequeira Catarina Oliveira , Pereira Sofia Azeredo , Guedes de Pinho Paula , Carvalho Félix , Sá Susana Isabel , Fernandes Eduarda , Costa Vera Marisa
Published: August 2023

Long-term cognitive dysfunction, or “chemobrain”, has been observed in cancer patients treated with chemotherapy. Mitoxantrone (MTX) is a topoisomerase II inhibitor that binds and intercalates with DNA, being used in the treatment of several cancers and multiple sclerosis. Although MTX can induce chemobrain, its neurotoxic mechanisms are poorly studied. This work aimed to identify the adverse outcome pathways (AOPs) activated in the brain upon the use of a clinically relevant cumulative dose of MTX. Three-month-old male CD-1 mice were given a biweekly intraperitoneal administration of MTX over the course of three weeks until reaching a total cumulative dose of 6 mg/kg. Controls were given sterile saline in the same schedule. Two weeks after the last administration, the mice were euthanized and their brains removed. The left brain hemisphere was used for targeted profiling of the metabolism of glutathione and the right hemisphere for an untargeted metabolomics approach. The obtained results revealed that MTX treatment reduced the availability of cysteine (Cys), cysteinylglycine (CysGly), and reduced glutathione (GSH) suggesting that MTX disrupts glutathione metabolism. The untargeted approach revealed metabolic circuits of phosphatidylethanolamine, catecholamines, unsaturated fatty acids biosynthesis, and glycerolipids as relevant players in AOPs of MTX in our in vivo model. As far as we know, our study was the first to perform such a broad profiling study on pathways that could put patients given MTX at risk of cognitive deficits.
Neutrophil-to-Lymphocyte Ratio, Neutrophil-to-Monocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune-Inflammation Index in Psoriasis Patients: Response to Treatment with Biological Drugs
Authors: Albayrak Hulya
Published: August 2023

Background: Psoriasis is a chronic immune-mediated skin disease in which systemic inflammation plays an important role in its pathogenesis. In recent years, the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were shown to be important indicators of inflammation. This study aimed to investigate the NLR, NMR, PLR, and SII levels in psoriasis patients treated with biological agents. Method: Clinical and biochemical data of 209 patients who received systemic therapy for psoriasis were obtained by retrospectively reviewing their medical records. The NLR, NMR, PLR, and SII values were calculated from the hemogram values of the patients. Results: In the third month of follow-up, the mean CRP, NLR, NMR, PLR, and SII values were significantly decreased compared with the baseline values. The SII values showed strong positive correlations with the NLR, NMR, and PLR. Adalimumab, etanercept, and infliximab, which are TNF-α blockers, were observed to be more effective on the PLR and NLR, and especially the NMR. Conclusions: The NLR, NMR, PLR, and SII, which are data derived from routine blood tests, can be used in the monitoring of the treatment of psoriasis, especially with TNF-α blockers.
Impact of Age on Endothelial Function of Saphenous Vein Grafts in Coronary Artery Bypass Grafting
Authors: Saemann Lars , Wernstedt Lena , Pohl Sabine , Stiller Markus , Willsch Jan , Hofmann Britt , Veres Gábor , Simm Andreas , Szabó Gábor
Published: August 2023

Background: An intact and functionally preserved endothelial layer in the graft is crucial for myocardial perfusion and graft patency after coronary artery bypass grafting (CABG). We hypothesized that old age is a risk factor for decreased endothelial function of bypass grafts. Thus, we investigated the impact of age in patients treated with CABG on endothelial function in saphenous vein grafts. Methods: We mounted the saphenous vein graft segments of CABG patients < 70 (n = 33) and ≥70 (n = 40) years of age in organ bath chambers and exposed them to potassium chloride (KCl) and phenylephrine (PE) to test the receptor-independent and -dependent contractility, followed by exposure to acetylcholine (ACh) and sodium nitroprusside (SNP) to test the endothelial-dependent and -independent relaxation. Results: The maximal contraction induced by KCl (2.3 ± 1.8 vs. 1.8 ± 2 g) was stronger in patients ≥ 70 years of age. The relative contraction induced by PE in % of KCl (167 ± 64 vs. 163 ± 59%) was similar between groups. Patients aged < 70 years showed a higher endothelial-dependent relaxation induced by acetylcholine than patients ≥ 70 years (51 ± 27 vs. 42 ± 18%). The relaxation induced by SNP was similar between both groups. Conclusions: The endothelial function of saphenous vein bypass grafts decreases during aging. Thus, age should be considered when improving graft maintenance.
The Usefulness of Cellular Immune Inflammation Markers and Ultrasound Evaluation in the Assessment of Disease Activity in Patients with Spondyloarthritis
Authors: Targońska-Stępniak Bożena , Grzechnik Krzysztof
Published: August 2023

Background: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) have been introduced as inflammatory markers and predictors of poor prognosis in cancer and cardiovascular diseases. An appropriate evaluation of disease activity in spondyloarthritis (SpA) might be challenging. The purpose of this study was to evaluate the usefulness of cellular immune inflammation markers and ultrasound (US) evaluation of entheses and joints in the assessment of disease activity in SpA patients. Methods: This cross-sectional study involved patients with SpA (62 axial SpA, 38 peripheral SpA, pSpA). The clinical data of both tender, swollen joint counts, erythrocyte sedimentation rate, C-reactive protein, white blood cell counts, and disease activity using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Index for Psoriatic Arthritis (DAPSA), were recorded. The SIRI, SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. US examination was performed (22 small joints, Achilles tendon, and plantar aponeurosis for enthesitis). Results: The SII, SIRI, NLR, and PLR were higher, and LMR was lower in patients with high disease activity (BASDAI > 4). Higher SII was observed in pSpA patients with moderate/high disease activity (DAPSA > 14). The SIRI was correlated with clinical and laboratory parameters of disease activity. The SII was correlated with US parameters in pSpA. Higher SII and NLR values were found in patients with signs of activity compared with no activity in the US of peripheral joints. There were no associations with US changes in entheses. Conclusions: The results of this study point to the value of SIRI and SII as biomarkers of disease activity in patients with SpA. The SII was associated with synovitis in the US of the peripheral joints.
Danazol as a Treatment for Uterine Arteriovenous Malformation: A Case Report
Authors: Tak Hyunjin , Lee Kyong-No , Ryu Ji-Won , Lee Keun-Young , Son Ga-Hyun
Published: August 2023

Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14–70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients.
Privacy, Property, and Third-Party Esteem in Arendt’s Constitutionalism
Authors: McGroarty Emmett , McGroarty Brendan
Published: August 2023

In On Revolution, Hannah Arendt makes the case that a constitution must account for the need of the human person to participate in the building of society, both as a primordial and continual action of founding. This paper draws on Arendt’s insight on the relationship between privacy and the notion of property, both of which the constitution must protect, as it is dependent on those notions. Property in its fullest sense is the means by which a person interacts with others and establishes a society. Particularly important for this notion of engagement are the concepts of shame and the love of goodness. The actor emerges from the private sphere to interact with others on the strength of the secrecy and confidentiality of her intimate, private relationships. Property is therefore essential to human flourishing and happiness. Following this, the activity of constructing the public forum on the basis of the private is an important feature of Arendt’s constitutionalism. Human Action showers third-party esteem on the actor’s family and friends, binding them to the constitutional structure and strengthening familial relationships and social cohesion.
Fresh Umbilical Cord Blood—A Source of Multipotent Stem Cells, Collection, Banking, Cryopreservation, and Ethical Concerns
Authors: Devi Seeta , Bongale Anupkumar M. , Tefera Minyechil Alehegn , Dixit Prashant , Bhanap Prasad
Published: August 2023

Umbilical cord blood (UCB) is a rich source of hematopoietic cells that can be used to replace bone marrow components. Many blood disorders and systemic illnesses are increasingly being treated with stem cells as regenerative medical therapy. Presently, collected blood has been stored in either public or private banks for allogenic or autologous transplantation. Using a specific keyword, we used the English language to search for relevant articles in SCOPUS and PubMed databases over time frame. According to our review, Asian countries are increasingly using UCB preservation for future use as regenerative medicine, and existing studies indicate that this trend will continue. This recent literature review explains the methodology of UCB collection, banking, and cryopreservation for future clinical use. Between 2010 and 2022, 10,054 UCB stem cell samples were effectively cryopreserved. Furthermore, we have discussed using Mesenchymal Stem Cells (MSCs) as transplant medicine, and its clinical applications. It is essential for healthcare personnel, particularly those working in labor rooms, to comprehend the protocols for collecting, transporting, and storing UCB. This review aims to provide a glimpse of the details about the UCB collection and banking processes, its benefits, and the use of UCB-derived stem cells in clinical practice, as well as the ethical concerns associated with UCB, all of which are important for healthcare professionals, particularly those working in maternity wards; namely, the obstetrician, neonatologist, and anyone involved in perinatal care. This article also highlights the practical and ethical concerns associated with private UCB banks, and the existence of public banks. UCB may continue to grow to assist healthcare teams worldwide in treating various metabolic, hematological, and immunodeficiency disorders.
Chemical Structure Comparison via Scanning Electron Microscopy of Spent Commercial Nickel–Metal Hydride Batteries
Authors: Walther Thomas
Published: August 2023

Back-scattered electron imaging and X-ray elemental mapping were combined in a tabletop scanning electron microscope (SEM) to investigate cross-sections of three AA-type (mignon) nickel–metal hydride (NiMH) batteries from different manufacturers. All batteries underwent 500–800 charge/discharge cycles and reached their end of lifetime after several years as they could no longer hold any significant electric charge (less than 20% of nominal charge capacity), but none showed any short-circuiting. The types of degradation observed in this field study included electrode swelling, metallic nickel formation and carbon incorporation into pores in the positive electrodes and, in the negative electrodes, metal alloy segregation of different elements such as nickel, lanthanum and, in one case, sodium, as well as grain break-up and pore formation. All these phenomena could readily be observed at rather small magnifications. This will be important for the improvement of NiMH batteries, for which new generations with nominally slightly increased charge capacities are being marketed all the time.
Quantification and Analysis of Residual Stresses in Braking Pedal Produced via Laser–Powder Bed Fusion Additive Manufacturing Technology
Authors: Fojtík František , Potrok Roman , Hajnyš Jiří , Ma Quoc-Phu , Kudrna Lukáš , Měsíček Jakub
Published: August 2023

This study focuses on the experimental verification of residual stress (RS) in a 3D-printed braking pedal using the Powder Bed Fusion (PBF) method with SS316L material. The RS was measured at two representative locations using the hole drilling method (HDM) and the dividing method, which are semi-destructive and destructive methods of RS measurement, respectively. The finite element method (FEM) was used with Ansys Workbench 2020R2 and Simufact Additive 2021 software to determine the magnitude of RS. The results provide insights into how RS is incorporated into metal 3D-printed components and the available tools for predicting RS. This information is essential for experts to improve the accuracy and functionality of SLM parts when post-subtractive or additive manufacturing processes are used. Overall, this study contributes to the advancement of knowledge on the effects of RS on 3D-printed metal components, which can inform future research and development in this area.
Assessment of the Composition Effect of a Bio-Cementation Solution on the Efficiency of Microbially Induced Calcite Precipitation Processes in Loose Sandy Soil
Authors: Fronczyk Joanna , Marchelina Nadella , Pyzik Adam , Franus Małgorzata
Published: August 2023

Soil properties are the most important factors determining the safety of civil engineering structures. One of the soil improvement methods studied, mainly under laboratory conditions, is the use of microbially induced calcite precipitation (MICP). Many factors influencing the successful application of the MICP method can be distinguished; however, one of the most important factors is the composition of the bio-cementation solution. This study aimed to propose an optimal combination of a bio-cementation solution based on carbonate precipitation, crystal types, and the comprehensive strength of fine sand after treatment. A series of laboratory tests were conducted with the urease-producing environmental strain of bacteria B. subtilis, using various combinations of cementation solutions containing precipitation precursors (H2NCONH2, C6H10CaO6, CaCl2, MgCl2). To decrease the environmental impact and increase the efficiency of MICP processed, the addition of calcium lactate (CaL) and Mg ions was evaluated. This study was conducted in Petri dishes, assuming a 14-day soil treatment period. The content of water-soluble carbonate precipitates and their mineralogical characterization, as well as their mechanical properties, were determined using a pocket penetrometer test. The studies revealed that a higher concentration of CaL and Mg in the cementation solution led to the formation of a higher amount of precipitates during the cementation process. However, the crystal forms were not limited to stable forms, such as calcite, aragonite, (Ca, Mg)-calcite, and dolomite, but also included water-soluble components such as nitrocalcite, chloro-magnesite, and nitromagnesite. The presence of bacteria allowed for the increasing of the carbonate content by values ranging from 15% to 42%. The highest comprehensive strength was achieved for the bio-cementation solution containing urea (0.25 M), CaL (0.1 M), and an Mg/Ca molar ratio of 0.4. In the end, this research helped to achieve higher amounts of precipitates with the optimum combination of bio-cementation solutions for the soil improvement process. However, the numerical analysis of the precipitation processes and the methods reducing the environmental impact of the technology should be further investigated.
Effect of Carbonation Treatment on the Properties of Steel Slag Aggregate
Authors: Ma Jian , Dai Guangjian , Jiang Feifei , Wang Ning , Zhao Yufeng , Wang Xiaodong
Published: August 2023

Steel slag is the waste slag generated after steel smelting, which has cementitious activity. However, untreated steel slag can damage the integrity of steel slag concrete due to its harmful expansion. This study prepared porous aggregates by mixing powdered steel slag, fly ash, and cement and carbonated them with CO2 under high pressure conditions (0.2 MPa). The effect of carbonation on the performance of steel slag aggregate was studied using volume stability and crushing value. The effect of different carbonation conditions on the products was studied using X-ray diffraction (XRD) and thermogravimetric (TG) analyses, and the carbon sequestration efficiency of steel slag under different treatment methods was quantitatively evaluated. The research results indicate that untreated steel slag was almost completely destroyed and lost its strength after autoclave curing. With the increase in temperature and carbonation time, the performance of steel slag aggregate gradually improved and the pulverization rate, expansion rate, and crushing value gradually decreased. According to the experimental results of XRD and TG, it was found that the reaction between f-CaO (free CaO) and CO2 in steel slag generated CaCO3, filling the pores inside the aggregate, which was the internal reason for the improvement of aggregate performance. After comparison, the best carbonation method was maintained at 55 °C for 72 h. After carbonation, the steel slag aggregate had a pulverization rate of 2.4%, an expansion rate of 0.23%, a crushing value of 23%, and a carbon sequestration efficiency of 11.27% per unit weight of aggregate.
Lithium Iron Phosphate and Layered Transition Metal Oxide Cathode for Power Batteries: Attenuation Mechanisms and Modification Strategies
Authors: Zhang Guanhua , Li Min , Ye Zimu , Chen Tieren , Cao Jiawei , Yang Hongbo , Ma Chengbo , Jia Zhenggang , Xie Jiwei , Cui Ning , Xiong Yueping
Published: August 2023

In the past decade, in the context of the carbon peaking and carbon neutrality era, the rapid development of new energy vehicles has led to higher requirements for the performance of strike forces such as battery cycle life, energy density, and cost. Lithium-ion batteries have gradually become mainstream in electric vehicle power batteries due to their excellent energy density, rate performance, and cycle life. At present, the most widely used cathode materials for power batteries are lithium iron phosphate (LFP) and LixNiyMnzCo1−y−zO2 cathodes (NCM). However, these materials exhibit bottlenecks that limit the improvement and promotion of power battery performance. In this review, the performance characteristics, cycle life attenuation mechanism (including structural damage, gas generation, and active lithium loss, etc.), and improvement methods (including surface coating and element-doping modification) of LFP and NCM batteries are reviewed. Finally, the development prospects of this field are proposed.
Drilling Sequence Optimization Using Evolutionary Algorithms to Reduce Heat Accumulation for Femtosecond Laser Drilling with Multi-Spot Beam Profiles
Authors: Lutz Christian , Helm Jonas , Tschirpke Katrin , Esen Cemal , Hellmann Ralf
Published: August 2023

We report on laser drilling borehole arrays using ultrashort pulsed lasers with a particular focus on reducing the inadvertent heat accumulation across the workpiece by optimizing the drilling sequence. For the optimization, evolutionary algorithms are used and their results are verified by thermal simulation using Comsol and experimentally evaluated using a thermal imaging camera. To enhance process efficiency in terms of boreholes drilled per second, multi-spot approaches are employed using a spatial light modulator. However, as higher temperatures occur across the workpiece when using simultaneous multi-spot drilling as compared to a single-spot process, a subtle spatial distribution and sequence of the multi-spot approach has to be selected in order to limit the resulting local heat input over the processing time. Different optimization approaches based on evolutionary algorithms aid to select those drilling sequences which allow for the combination of a high efficiency of multi-spot profiles, a low-generated process temperature and a high-component quality. In particular, using a 4 × 4 laser spot array allows for the drilling of 40,000 boreholes in less than 76 s (526 boreholes/s) with a reduced temperature increase by about 35%, as compared to a single spot process when employing an optimized drilling sequence.
A Novel Nickel-Plated Carbon Fiber Insert in Aluminum Joints with Thermoplastic ABS Polymer or Stainless Steel
Authors: Nishi Yoshitake , Sagawa Kouhei , Faudree Michael C. , Uchida Helmut Takahiro , Kanda Masae , Kaneko Satoru , Salvia Michelle , Matsumura Yoshihito , Kimura Hideki
Published: August 2023

New types of hybrid aluminum joints: Al-acrylonitrile butadiene styrene (ABS) carbon fiber reinforced thermoplastic polymer (CFRTP) designated Al/Ni-CFP/ABS, and Al-18-8 Stainless steel, Al/Ni-CFP/18-8, by Ni-plated carbon fiber plug (Ni-CFP) insert not before seen in the literature have been fabricated. The goal is to take advantage of extremely high ~6 mm CF surface area for high adhesion, to enhance the safety level of aircraft and other parts. This is without fasteners, chemical treatment, or glue. First, the CFP is plated with Ni. Second, the higher melting point half-length is spot welded to the CFP; and third, the remaining half-length is fabricated. The ultimate tensile strength (UTS) of Al/Ni-CFP/ABS was raised 15 times over that of Al/ABS. Normalized cUTS according to CFP cross-section by Rule of Mixtures for cAl/Ni-CFP/18-8 was raised over that of cAl/Ni-CFP/18-8 from 140 to 360 MPa. Resistance energy to tensile deformation, UT, was raised 12 times from Al/ABS to Al/Ni-CFP/ABS, and 6 times from Al/CFP/18-8 to Al/Ni-CFP/18-8. Spot welding allows rapid melting followed by rapid solidification for amorphous metal structures minimizing grain boundaries. The Ni-coating lowers or counters the effects of brittle Al4C3 and FexC formation at the interface and prevents damage by impingement to CFs, allowing joints to take on more of the load.
Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases—A Review
Authors: Liyanage N. M. , Nagahawatta D. P. , Jayawardena Thilina U. , Sanjeewa Kalu Kapuge Asanka , Jayawrdhana H. H. A. C. K. , Kim Jae-Il , Jeon You-Jin
Published: August 2023

The limited availability of treatments for many infectious diseases highlights the need for new treatments, particularly for viral infections. Natural compounds from seaweed are attracting increasing attention for the treatment of various viral diseases, and thousands of novel compounds have been isolated for the development of pharmaceutical products. Seaweed is a rich source of natural bioactive compounds, including polysaccharides. The discovery of algal polysaccharides with antiviral activity has significantly increased in the past few decades. Furthermore, unique polysaccharides isolated from seaweeds, such as carrageenan, alginates, fucoidans, galactans, laminarians, and ulvans, have been shown to act against viral infections. The antiviral mechanisms of these agents are based on their inhibition of DNA or RNA synthesis, viral entry, and viral replication. In this article, we review and provide an inclusive description of the antiviral activities of algal polysaccharides. Additionally, we discuss the challenges and opportunities for developing polysaccharide-based antiviral therapies, including issues related to drug delivery and formulation. Finally, this review highlights the need for further research for fully understanding the potential of seaweed polysaccharides as a source of antiviral agents and for developing effective treatments for viral diseases.
Safe and Efficient Use of Tocilizumab in Rheumatoid Arthritis Patient on Maintenance Hemodialysis: A Case Report
Authors: Kilić Paula , Ikić Lucija , Mayer Miroslav , Artuković Marinko , Maštrović Radončić Ksenija , Ikić Matijašević Marina
Published: August 2023

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune and inflammatory disease. Conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), Janus kinase inhibitors, and rituximab are used to treat the disease. There are no recommendations or guidelines for the treatment of patients with both inflammatory arthritis and end-stage renal disease (ESRD), despite the safety and efficacy of the mentioned drugs. The anti-interleukin-6 receptor antibody tocilizumab (TCZ) has not been used as a long-term therapy for hemodialysis (HD) patients with RA, except in a few case reports. Case Description: We present the case of a 41-year-old patient with RA and ESRD on maintenance HD due to type 1 diabetes-related complications. Due to high RA disease activity, the patient was not a suitable candidate for a kidney transplant. Because TCZ is used to treat both RA and kidney transplant rejection, therapy with a full dose of TCZ was administered. The patient has achieved sustained clinical remission (for the past four years) with no adverse events reported. Conclusions: Herein, we present the safe and effective use of TCZ in an RA patient on HD who is also a candidate for kidney transplant. Consequently, TCZ could be the treatment of choice for RA patients with ESRD who have not achieved disease control (low activity or remission) with conventional synthetic DMARDs. Clinical studies are required to evaluate the efficacy and safety of biologic DMARDs and Janus kinase inhibitors in patients with both inflammatory arthritis and ESRD.
Optimization of Oxygen Injection Conditions with Different Molten Steel Levels in the EAF Refining Process by CFD Simulation
Authors: Thongjitr Perawat , Kowitwarangkul Pruet , Pratumwal Yotsakorn , Otarawanna Somboon
Published: August 2023

In electric arc furnace (EAF) steelmaking, oxygen jets play a crucial role in controlling stirring ability, chemical reactions, and energy consumption. During the EAF lifetime, refractory wear leads to a decrease in the molten steel level and an increase in the nozzle-to-steel distance, thereby negatively affecting the overall energy efficiency of the process. The objective of this study is to optimize the energy efficiency of the EAF refining process by adjusting the nozzle flow conditions and conducting an analysis of jet performance using computational fluid dynamics (CFD) simulation. Three types of injection jets were considered: the conventional jet, the CH4 coherent jet, and the CH4 + O2 coherent jet. The findings reveal that the shrouded flame of the coherent jet enhances jet performance by maintaining the maximum velocity, extending the potential core length, and increasing the penetration depth in the molten steel bath. To maintain the jet performance in response to an increased nozzle-to-steel distance resulting from refractory wear, transitions from the conventional jet to the CH4 coherent jet and the CH4 + O2 coherent jet are recommended once the nozzle-to-steel distance increases from its initial level of 1000 mm to 1500 mm and 2000 mm, respectively.
The Characterization of Coatings Formed on As-Cast Al, Al–Si, and Al–Ca Aluminum Substrates by Plasma Electrolytic Oxidation
Authors: Letyagin Nikolay V. , Akopyan Torgom K. , Sokorev Alexander A. , Sviridova Tatiana A. , Cherkasov Stanislav O. , Mansurov Yulbarskhon N.
Published: August 2023

In this study, ceramic coatings were grown on the surface of as-cast aluminum alloys via plasma electrolytic oxidation (PEO). The effect of the Si- and Ca-alloying elements in aluminum on the growth process, morphology, composition, mechanical, and corrosion properties of the PEO coatings was investigated. Uniform coatings with a minimum number of defects were formed on the surfaces of Al–Ca alloys. Increasing the Si content in Al led to an increase in the bulk and surface porosity of the coatings. The α-Al2O3 phase mainly formed in the coatings synthesized on pure Al and Al–Ca alloys, while an increased amount of Si in Al alloys hindered the formation of the α-Al2O3 phase. The coatings had a microhardness of 660–1180 HV, which was 20–30 times higher than that of the original as-cast alloy. Moreover, the coating on the Al–Ca alloys had the highest peak hardness, which was probably caused by the formation of a greater amount of the α-Al2O3 phase. Electrochemical studies in 3.5% NaCl have shown that PEO coatings reduce the corrosion current density. Of all PEO-treated alloys, Al and Al1Ca have the lowest corrosion current density and hence the highest corrosion resistance due to the composition and uniformity of the coating.
Characteristics of Convective Parameters Derived from Rawinsonde and ERA5 Data Associated with Hailstorms in Northeastern Romania
Authors: Istrate Vasilică , Podiuc Dorin , Sîrbu Dragoș Andrei , Popescu Eduard , Sîrbu Emil , Popescu Doru Dorian
Published: August 2023

Using a database of 378 hail days between 1981 and 2020, the climatic characteristics of 23 convective parameters from sounding data and ERA5 data were statistically analysed. The goal of this work is to evaluate the usefulness and representativeness of convective parameters derived from sounding data and reanalysis data for the operational forecast of the hail phenomenon. As a result, the average values from 12:00 UTC were 433 J/kg for CAPE in the case of data from ERA5 and 505 J/kg from rawinsonde, respectively. The Spearman correlation coefficient matrix between the values of the parameters indicates high correlations among the parameters calculated based on the parcel theory, humidity indices, and the complex indices. The probability for large hail increases with high values of low-level and boundary-layer moisture, high CAPE, and a high lifting condensation level (LCL) height.