bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Impulsivity Traits and In Vivo Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in Healthy Individuals: A Double-Tracer PET Study with C-11 DASB and C-11 MDL100907
Authors: Kim Jeong-Hee , Kim Hang-Keun , Son Young-Don , Kim Jong-Hoon
Published: December 2024

To elucidate the potential roles of presynaptic and postsynaptic serotonergic activity in impulsivity traits, we investigated the relationship between self-reported impulsiveness and serotonin transporter (5-HTT) and 5-HT2A receptors in healthy individuals. In this study, 26 participants completed 3-Tesla magnetic resonance imaging and positron emission tomography with [11C]DASB and [11C]MDL100907. To quantify 5-HTT and 5-HT2A receptor availability, the binding potential (BPND) of [11C]DASB and [11C]MDL100907 was derived using the simplified reference tissue model with cerebellar gray matter as the reference region. The participants’ impulsivity levels were assessed using the Barratt Impulsiveness Scale-11 (BIS-11). The region of interest (ROI)-based partial correlation analysis with age, sex, and temperament traits as covariates revealed a significant positive correlation between non-planning impulsiveness and [11C]MDL100907 BPND in the caudate (CAU) at Bonferroni-corrected p < 0.0045. Non-planning impulsiveness was also positively correlated with [11C]MDL100907 BPND in the prefrontal cortex (PFC), ventromedial PFC, orbitofrontal cortex (OFC), insula (INS), amygdala (AMYG), putamen, ventral striatum, and thalamus, and the total score of BIS-11 was positively correlated with [11C]MDL100907 BPND in the OFC, INS, AMYG, and CAU at uncorrected p < 0.05. Motor impulsiveness had a positive correlation with [11C]DASB BPND in the CAU at uncorrected p < 0.05. Our results suggest that impulsivity traits, characterized by focusing on the present moment without considering future consequences, may be involved in serotonergic neurotransmission, particularly 5-HT2A receptor-mediated postsynaptic signaling in the CAU, which plays an important role in cognitive processes related to executive function, judgment of alternative outcomes, and inhibitory control.
Cellular Response of Immune Cells in the Upper Respiratory Tract After Treatment with Cold Atmospheric Plasma In Vitro
Authors: Reichold Leonardo Zamorano , Gruber Michael , Unger Petra , Maisch Tim , Lindner Regina , Gebhardt Lisa , Schober Robert , Karrer Sigrid , Arndt Stephanie
Published: December 2024

Cold atmospheric plasma (CAP) has antimicrobial properties and is also known to stimulate the immune system. These properties could be useful for the development of a novel therapeutic or preventive strategy against respiratory infections in the upper respiratory tract (URT) such as ventilator-associated pneumonia (VAP) without inducing an immune overreaction. This study investigated the cellular responses of polymorphonuclear neutrophils (PMNs) after exposure to CAP in a three-dimensional (3D) model of the URT. In vitro experiments were conducted using PMNs isolated from human blood to assess cell migration, intracellular production of reactive oxygen species (ROS), NETosis, surface marker expression (CD11b, CD62L, and CD66b), and cell death with live cell imaging and flow cytometry. CAP was applied for 5 min using two distinct modalities: pressurized air plasma with a plasma intensive care (PIC) device and nebulized air plasma (NP) with a new humidity resistent surface microdischarge (SMD) plasma source, both developed by Terraplasma Medical GmbH. There were no significant signs of cell damage or overstimulation with either device under the conditions tested. However, the NP device caused milder effects on PMN functionality compared to the PIC device, but also demonstrated reduced antibacterial efficacy and reactive oxygen/nitrogen species (RONS) production, as analyzed with colorimetric/fluorimetric assay kits. These findings highlight a trade-off between the two CAP modalities, each with distinct advantages and limitations. Further studies are necessary to investigate these effects in the clinical setting and evaluate the long-term safety and efficacy of CAP treatment in the URT.
Design and Characterization of Novel Polymeric Hydrogels with Protein Carriers for Biomedical Use
Authors: Kędzierska Magdalena , Bańkosz Magdalena , Sala Katarzyna , Garbowska Claudia , Grzywacz Oliwia , Wrzesińska Wiktoria , Liber-Kneć Aneta , Potemski Piotr , Tyliszczak Bożena
Published: December 2024

Hydrogels are three-dimensional polymeric matrices capable of absorbing significant amounts of water or biological fluids, making them promising candidates for biomedical applications such as drug delivery and wound healing. In this study, novel hydrogels were synthesized using a photopolymerization method and modified with cisplatin-loaded protein carriers, as well as natural extracts of nettle (Urtica dioica) and chamomile (Matricaria chamomilla L.). The basic components of the hydrogel were polyvinylpyrrolidone and polyvinyl alcohol, while polyethylene glycol diacrylate was used as a crosslinking agent and 2-methyl-2-hydroxypropiophenone as a photoinitiator. The hydrogels demonstrated high swelling capacities, with values up to 4.5 g/g in distilled water, and lower absorption in Ringer’s solution and simulated body fluid (SBF), influenced by ionic interactions. Wettability measurements indicated water contact angles between 51° and 59°, suggesting balanced hydrophilic properties conducive to biomedical applications. Surface roughness analyses revealed that roughness values decreased after incubation, with Ra values ranging from 6.73 µm before incubation to 5.94 µm after incubation for samples with the highest protein content. Incubation studies confirmed the stability of the hydrogel matrix, with no significant structural degradation observed over 20 days. However, hydrogels containing 2.0 mL of protein suspension exhibited structural damage and were excluded from further testing. The synthesized hydrogels show potential for application as carriers in localized drug delivery systems, offering a platform for future development in areas such as targeted therapy for skin cancer or other localized treatments.
Biomarkers of Extracellular Matrix Fragments in Patients with Psoriasis
Authors: Johansen Mila Broby , Nielsen Signe Holm , Port Helena , Todberg Tanja , Løvendorf Marianne Bengtson , Skov Lone
Published: December 2024

Blood-based extracellular matrix (ECM) fragments have been identified as potential pharmacologic biomarkers in spondyloarthritis and diagnostic biomarkers in psoriatic arthritis and psoriasis vulgaris. This study aimed to explore whether ECM fragments can differentiate patients with psoriasis from healthy controls (HC) and determine their potential as biomarkers for response to treatment in psoriasis. The study population included 59 patients with moderate to severe psoriasis, not receiving systemic anti-psoriatic treatment at inclusion, and 52 HC matched by age, sex, and BMI. An EDTA plasma sample was taken from all subjects at inclusion. Nine patients with psoriasis who initiated treatment with adalimumab after inclusion and responded successfully had an additional EDTA plasma sample taken after three to six months. Twelve ECM fragments were measured using validated ELISAs and Immunodiagnostic Systems automated chemiluminescent assays. C4M, indicating collagen IV degradation, PRO-C3, indicating tissue fibrosis, and PRO-C4, indicating epidermal basement membrane turnover showed significantly elevated levels in psoriasis patients compared with HC (p = 0.005, p = 0.016, and p = 0.018, respectively). Despite successful treatment, adalimumab did not alter C4M, PRO-C3, or PRO-C4 levels. In conclusion, compared with controls, C4M, PRO-C3, and PRO-C4 were elevated in psoriasispatients, but treatment did not modulate these fragments.
Correction: Qin et al. Production and Stabilization of Specific Upregulated Long Noncoding RNA HOXD-AS2 in Glioblastomas Are Mediated by TFE3 and miR-661, Respectively. Int. J. Mol. Sci. 2022, 23, 2828
Authors: Qin Yiming , Qi Yingjiao , Zhang Xin , Guan Zhiang , Han Wei , Peng Xiaozhong
Published: December 2024

The authors wish to make the following correction to this paper [...]
Preventive Effects of Resistance Training on Hemodynamics and Kidney Mitochondrial Bioenergetic Function in Ovariectomized Rats
Authors: Queiroz Anne L. F. , Garcia Christopher B. , Silva João P. M. O. , Cavalini Diego F. A. , Alexandrino André V. , Cunha Anderson F. , Vercesi Anibal E. , Castilho Roger F. , Shiguemoto Gilberto E.
Published: December 2024

Menopause occurs due to the depletion of the ovarian reserve, leading to a progressive decline in estrogen (E2) levels. This decrease in E2 levels increases the risk of developing several diseases and can coexist with chronic kidney disease (CKD). Arterial hypertension (AH) is another condition associated with menopause and may either contribute to or result from CKD. Ovariectomy (OVX) induces hypoestrogenism, which can lead to mitochondrial bioenergetic dysfunction in the kidneys. Previous studies have suggested that exercise training has beneficial effects on adults with CKD and AH. To investigate the effects of OVX and resistance training (RT) on hemodynamic parameters and mitochondrial bioenergetic function of the kidney, female Wistar rats were divided into ovariectomized (OVX) and intact (INT) groups. These rats were either kept sedentary (SED) or subjected to RT for thirteen weeks. The RT involved climbing a vertical ladder with a workload apparatus. Hemodynamic parameters were assessed via tail plethysmography. Mitochondrial respiratory function was evaluated with high-resolution respirometry. Gene expression related to the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) was evaluated by real-time qPCR. At week 13, key hemodynamic parameters (systolic blood pressure and mean arterial pressure) were significantly elevated in the OVX-SED group. Compared with those in the other groups, mitochondrial bioenergetics were impaired in the OVX-SED group. In contrast, the trained groups presented improved mitochondrial bioenergetic function compared with the sedentary groups. OVX led to reduced gene expression related to the mitochondrial ETC and OXPHOS, whereas RT both prevented this reduction and increased gene expression in the trained groups. Our results indicate that hypoestrogenism significantly decreases OXPHOS and ETC capacity in the kidneys of sedentary animals. However, RT effectively increased the expression of genes related to mitochondrial ETC and OXPHOS, thereby counteracting the effects of OVX.
Special Issue on Nanoparticles in Nanobiotechnology and Nanomedicine
Authors: Caizer Costica
Published: December 2024

In the present day [...]
Platelet Mitochondrial Function and Endogenous Coenzyme Q10 Levels Could Be Used as Markers of Mitochondrial Health in Infertile Men: A Pilot Study
Authors: Sumbalová Zuzana , Rausová Zuzana , Kucharská Jarmila , Šranko Patrik , Harbulák Peter , Svitok Pavel , López-Lluch Guillermo , Gvozdjáková Anna
Published: December 2024

Fertility disorders are a worldwide problem affecting 8–12% of the population, with the male factor substantially contributing to about 40–50% of all infertility cases. Mitochondria, crucial organelles for cellular viability, play a pivotal role in the processes of spermatogenesis and significantly affect sperm quality and their fertilizing ability. Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, reduced energy supply for sperm, reduced endogenous coenzyme Q10 (CoQ10) levels, and oxidative stress are among the main factors that contribute to male infertility. There is great interest in the role of mitochondrial dysfunction in male infertility, and the diagnosis and assessment of mitochondrial health in infertile men present challenges. Platelets are a source of viable mitochondria that can be obtained non-invasively. Changes in platelet mitochondrial respiration were documented in various diseases, confirming platelet mitochondrial bioenergetics as a marker of systemic mitochondrial health. The aim of our study was to determine whether (a) platelet mitochondrial bioenergetics and CoQ10 levels could be used as metabolic markers of mitochondrial health in infertile men and whether (b) the parameters of mitochondrial respiration in platelets correlate with sperm parameters. The high-resolution respirometry method was used for platelet bioenergetics, and the high-performance liquid chromatography (HPLC) method was used for CoQ10 level measurement. The static oxidation–reduction potential (sORP) of the ejaculate was evaluated by MiOXSYS®System. We found a deficit in mitochondrial complex I-linked OXPHOS and electron transfer capacity and CoQ10 and α-tocopherol levels in infertile men. The proportion of sperm, heads, and midpiece abnormalities correlated negatively with the complex I-linked parameters of platelet mitochondrial bioenergetics. We suppose that dysfunctional mitochondria contribute to increased oxidative stress, and these imbalances can be considered a cause of Male Oxidative Stress Infertility (MOSI). Our results suggest that platelet mitochondrial function and the endogenous levels of CoQ10 in platelets could be used as metabolic markers for monitoring mitochondrial health and targeted therapy in infertile men. sORP could be a useful clinical biomarker of MOSI.
Diastolic Dysfunction with Normal Ejection Fraction and Reduced Heart Rate in Mice Expressing Human Growth Hormone and Displaying Signs of Growth Hormone Insufficiency
Authors: Jin Yan , Xiang Bo , Dolinsky Vernon W. , Kardami Elissavet , Cattini Peter A.
Published: December 2024

Growth hormone (GH) signaling is essential for heart development. Both GH deficiency and excess raise cardiovascular risk. Human (h) and mouse (m) GH differ structurally and functionally: hGH binds both the GH receptor (GHR) and prolactin receptor (PRLR), whereas mGH binds only GHR; thus, there is the potential for differential effects. We generated transgenic (hGH-TG) mice that produce pituitary hGH in response to hypothalamic signaling. These mice grow at the same rate as mGH-expressing wild-type (mGH-WT) mice but are smaller and have higher body fat. Echocardiography was used here to compare hGH-TG and mGH-WT mouse hearts. Male hGH-TG mice show a 48% lower left ventricular mass, 36% lower stroke volume, and 48% reduced cardiac output, resembling GH deficiency. Diastolic dysfunction, restrictive ventricular filling, and lower heart rate are suggested in hGH-TG mice. No significant differences in ejection fraction or fractional shortening were observed, even after high-fat diet (HFD) stress. HFD did not affect RNA markers of cardiac damage, although a possible association between B-type natriuretic peptide RNA levels and heart rate was detected. These observations suggest that diastolic dysfunction related to hGH and/or low GH might be offset by a lower heart rate, while structural changes precede functional effects.
Biomarkers for the Molecular Diagnosis of IgE-Mediated Hymenoptera Venom Allergy in Clinical Practice
Authors: Popescu Florin-Dan , Preda Mariana , Antolín-Amérigo Darío , Rodríguez-Otero Natalia , Ramírez-Mateo Elena , Smolinska Sylwia
Published: December 2024

Hymenoptera venom allergy (HVA) is a potentially life-threatening condition, making accurate diagnosis crucial for identifying significant IgE sensitizations and enabling effective venom immunotherapy. In this review, we provide a detailed overview of biomarkers for the molecular diagnosis of IgE-mediated hypersensitivity to Hymenoptera insect venoms in clinical practice, and we present, in a structured manner, their importance in differentiating genuine sensitizations versus cross-sensitizations using different diagnostic procedures. Updated algorithms are provided, along with the advantages and limitations of molecular diagnosis approaches. Geographical variations and rare species may pose further challenges in diagnosing and treating HVA, adding complexity to HVA management. This review informs readers about performing tailored diagnostics based on molecular allergen biomarkers and subsequent treatment strategies.
Mustard Meal Extract as an Alternative to Zinc Oxide for Protecting the Intestinal Barrier Against E. coli-Lipopolysaccharide Damage
Authors: Taranu Ionelia , Bulgaru (Procudin) Cristina Valeria , Pistol Gina Cecilia , Gras Mihai Alexandru , Ciupitu Ana-Maria , Grosu Iulian Alexandru , Vlassa Mihaela , Filip Miuta , Marin Daniela Eliza
Published: December 2024

The present study aimed to investigate the ability of an aqueous extract derived from mustard seed meal to counteract the effects of E. coli endotoxin lipopolysaccharide (LPS) on the intestinal epithelium. Caco-2 cells were cultured together with HT29-MTX and used as a cellular model to analyze critical intestinal parameters, such as renewal, integrity, innate immunity, and signaling pathway. Byproducts of mustard seed oil extraction are rich in soluble polysaccharides, proteins, allyl isothiocyanates, and phenolic acids, which are known as powerful antioxidants with antimicrobial and antifungal properties. Cells were seeded at a ratio of nine (Caco-2) to one (HT29-MXT) and treated for 2 h with mustard meal extract (ME, dilution 1/50) and zinc oxide (ZnO, 50 μM) after reaching 80–100% confluence. Then, they were challenged with 5 μg/mL E. coli-LPS and incubated for another 4 h. The results show that LPS did not alter the cell viability but decreased proliferation compared to the control, ME and ZnO treatments. LPS altered the cell membrane integrity and monolayer permeability by decreasing the transepithelial electrical resistance and tight-junction protein expression. In addition, LPS increased the activity of LDH and the expression of Toll-like receptors. The mechanisms by which LPS induces these disturbances involves the overexpression of PKC, p38 MAPK, and NF-κB signaling molecules. The pretreatment with mustard meal and ZnO succeeded in counteracting the impairment of epithelial renewal, the damage of the membrane integrity and permeability as well as in restoring the gene expression of tight-junction proteins.
Human miR-1 Stimulates Metabolic and Thermogenic-Related Genes in Adipocytes
Authors: Díez-Sainz Ester , Milagro Fermín I. , Aranaz Paula , Riezu-Boj José I. , Batrow Pierre-Louis , Contu Laura , Gautier Nadine , Amri Ez-Zoubir , Mothe-Satney Isabelle , Lorente-Cebrián Silvia
Published: December 2024

MicroRNAs play a pivotal role in the regulation of adipose tissue function and have emerged as promising therapeutic candidates for the management of obesity and associated comorbidities. Among them, miR-1 could be a potential biomarker for metabolic diseases and contribute to metabolic homeostasis. However, thorough research is required to fully elucidate the impact of miR-1 on human adipocyte thermogenesis and metabolism. This study aimed to explore the effect of miR-1 on human adipocyte browning, a process whose activation has been linked to obesity protection and counteraction. Human multipotent adipose-derived stem cells, hMADS cells, were differentiated into white and brown-like adipocytes and transfected with miR-1 mimics for gene expression and western blotting analyses. miR-1 inhibited the expression of its previously validated target PTK9/TWF1 and modulated the expression profile of key genes involved in thermogenesis and adipocyte browning (increased UCP1 at mRNA and protein level, increased CPT1M, decreased HIF3A), adipocyte differentiation and metabolism (decreased PLIN1, FASN, RXRA, PPARG, FABP4, MAPKAPK2), as well as genes related to the cytoskeleton (decreased ACTB) and extracellular matrix (decreased COL1A1). These findings suggest that miR-1 can modulate the expression of adipocyte human genes associated with thermogenesis and metabolism, which could hold value for eventual therapeutic potential in obesity.
PmbHLH58 from Pinus massoniana Improves Drought Tolerance by Reducing Stomatal Aperture and Inducing ABA Receptor Family Genes in Transgenic Poplar Plants
Authors: Zhang Jinfeng , Peng Manqing , Chen Peizhen , Yao Sheng , He Yuan , Wang Dengbao , Agassin Romaric Hippolyte , Ji Kongshu
Published: December 2024

The basic helix–loop–helix (bHLH) family members are involved in plant growth and development, physiological metabolism, and various stress response processes. Pinus massoniana is a major turpentine-producing and wood-producing tree in seasonally dry areas of southern China. Its economic and ecological values are well known. The forestry industry holds it in exceptionally high regard. Drought severely limits the growth and productivity of P. massoniana, and the functional role of PmbHLH58 in drought stress is not clear. Therefore, PmbHLH58 was cloned from P. massoniana and its bioinformation was analyzed. Subcellular mapping of the gene was performed. The biological function of PmbHLH58 overexpression in Populus davidiana × P. bolleana was studied. The results show that the drought tolerance of PmbHLH58-overexpressed poplar was significantly improved, which may be due to the increase in water use efficiency and reactive oxygen species (ROS) accumulation under drought stress. In an ethylene-responsive manner, PmERF71 interacted with the PmbHLH58 protein, which was found by yeast two-hybridization. We further demonstrated that the drought-induced PmbHLH58 transcription factor increased the expression of key enzyme genes in ABA receptor family genes in PmbHLH58-overexpressing poplar lines (OE). These findings provide new insights into transcriptional regulation mechanisms related to drought stress and will promote the progression of the genetic improvement and plantation development of P. massonsiana.
The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect
Authors: Guan Xiaoqun , Fury Hope , Issuree Priya D. , Atagozli Tyler , McManimon Emory E. , Shao Peng , Li Yue , Chimenti Michael , Butler Noah S. , Kaplan Mark H. , Elliott David E. , Blazar Bruce R. , Ince M. Nedim
Published: December 2024

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD. As the T helper-2 (Th2) pathway is critical to helminthic immune regulation, we asked whether the genetic induction of Th2 signaling in donor T cells can restore helminthic immune regulation after BMT. Our studies utilized transgenic donor T lymphocytes that overexpress a constitutively active form of the Th2-associated transcription factor STAT6. Constitutively active STAT6 sustained the GVT response without causing severe acute GVHD, where transgenic T cells generated robust quantities of cytotoxic proteins important in GVT response, such as granzymes A and B, interferon-γ and Fas ligand, in addition to generating high quantities of Th2/regulatory cytokines. Bioinformatic analysis based on chromosome immune precipitation experiments indicated that STAT6 stimulates the expression of granzymes directly. Thus, in preserving the GVT response without causing GVHD mortality, our results indicate the therapeutic potential of restoring helminthic immune modulation by targeting STAT6 and STAT6-dependent T cell maturation.
Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells
Authors: Hsueh Yu-Huan , Chen Kuan-Po , Buddhakosai Waradee , Le Phung-Ngan , Hsiung Ying-Wu , Tu Yung-Yi , Chen Wen-Liang , Lu Huai-En , Tu Yuan-Kun
Published: December 2024

Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from H2O2-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies.
Evaluation of the Anti-Amyloid and Anti-Inflammatory Properties of a Novel Vanadium(IV)–Curcumin Complex in Lipopolysaccharides-Stimulated Primary Rat Neuron-Microglia Mixed Cultures
Authors: Katsipis Georgios , Lavrentiadou Sophia N. , Geromichalos George D. , Tsantarliotou Maria P. , Halevas Eleftherios , Litsardakis George , Pantazaki Anastasia A.
Published: December 2024

Lipopolysaccharides (LPS) are bacterial mediators of neuroinflammation that have been detected in close association with pathological protein aggregations of Alzheimer’s disease. LPS induce the release of cytokines by microglia and mediate the upregulation of inducible nitric oxide synthase (iNOS)—a mechanism also associated with amyloidosis. Curcumin is a recognized natural medicine but has extremely low bioavailability. V-Cur, a novel hemocompatible Vanadium(IV)-curcumin complex with higher solubility and bioactivity than curcumin, is studied here. Co-cultures consisting of rat primary neurons and microglia were treated with LPS and/or curcumin or V-Cur. V-Cur disrupted LPS-induced overexpression of amyloid precursor protein (APP) and the in vitro aggregation of human insulin (HI), more effectively than curcumin. Cell stimulation with LPS also increased full-length, inactive, and total iNOS levels, and the inflammation markers IL-1β and TNF-α. Both curcumin and V-Cur alleviated these effects, with V-Cur reducing iNOS levels more than curcumin. Complementary insights into possible bioactivity mechanisms of both curcumin and V-Cur were provided by In silico molecular docking calculations on Aβ1-42, APP, Aβ fibrils, HI, and iNOS. This study renders curcumin-based compounds a promising anti-inflammatory intervention that may be proven a strong tool in the effort to mitigate neurodegenerative disease pathology and neuroinflammatory conditions.
Peptide AEDL and Glutathione Stimulates Root Development Nicotiana tabacum
Authors: Kononenko Neonila Vasilievna , Fedoreyeva Larisa Ivanovna
Published: December 2024

Reactive oxygen species (ROS) are essential molecules involved in intercellular communication, signal transduction, and metabolic processes. Abiotic stresses cause the accumulation of excess ROS in plant cells. The issue of regulating the antioxidant protection of plants using natural and synthetic compounds with antioxidant activity still remains one of the most important and relevant areas of fundamental and applied research. Glutathione (GSH) plays an important role in the stress resistance and redox homeostasis of plant cells and effectively protects the cell from the stress-induced generation of ROS. An increase in the GSH content in plant cells can contribute to an increase in plant resistance to various types of stressors. We have shown that growing Nicotiana tabacum in the presence of tetrapeptide AEDL (AlaGluAspLeu) contributes to an increase in the GSH content by 3.24 times. At the same time, the tobacco plant was more developed, especially its root system. A scheme of the mechanism behind the regulation of the redox balance in the stem cell niche and the participation of the AEDL and GSH peptides in the regulation of the fate of stem cells was proposed.
Leukocyte Telomere Length as a Marker of Chronic Complications in Type 2 Diabetes Patients: A Risk Assessment Study
Authors: Sawicki Krzysztof , Matysiak-Kucharek Magdalena , Gorczyca-Siudak Daria , Kruszewski Marcin , Kurzepa Jacek , Kapka-Skrzypczak Lucyna , Dziemidok Piotr
Published: December 2024

Telomere shortening has been linked to type 2 diabetes (T2D) and its complications. This study aims to determine whether leukocyte telomere length (LTL) could be a useful marker in predicting the onset of complications in patients suffering from T2D. Enrolled study subjects were 147 T2D patients. LTL was measured using a quantitative PCR method. Key subject’s demographics and other clinical characteristics were also included. T2D patients with the shortest LTL had higher TC and non-HDL levels, compared to subjects with the longest LTL (p = 0.013). Also, T2D patients suffering from diabetic nephropathy showed significant differences in LDL levels (p = 0.023). While in the group of T2D patients with diabetic retinopathy, significant differences were observed for parameters, such as duration of diabetes (p = 0.043), HbA1c (p = 0.041), TC (p = 0.003), LDL (p = 0.015), Non-HDL (p = 0.004) and TG (p = 0.045). Logistic regression analysis confirmed a significant risk of association of TC and Non-HDL levels with LTL in the 3rd tertile LTL for the crude model adjusted for sex and age, with respective odds ratios of 0.71 (95% CI 0.56–0.91) and 0.73 (95% CI 0.58–0.91). No significant associations were found between LTL in T2D patients and the prevalence of common T2D complications. Nevertheless, a significant association was demonstrated between LTL and some markers of dyslipidemia, including in T2D patients with either diabetic nephropathy or retinopathy. Therefore, analysis of LTL in T2D patients’ leukocytes demonstrates a promising potential as a marker in predicting the onset of complications in T2D. This could also help in establishing an effective treatment strategy or even prevent and delay the onset of these severe complications.
Assessment of Hypercoagulability in Splanchnic Vein Thrombosis by Measurement of the Hemostasis Enzymes Thrombin and Activated Protein C
Authors: Reda Sara , Chang Johannes , Busse Johanna , Schwarz Nadine , McRae Hannah L. , Müller Jens , Strassburg Christian P. , Oldenburg Johannes , Pötzsch Bernd , Jansen Christian , Rühl Heiko
Published: December 2024

Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN−, and 30 healthy controls. Direct measurement of the active enzyme forms of thrombin and APC in the circulation was achieved by using oligonucleotide-based enzyme capture assays (OECA). Additionally, activation markers of coagulation and fibrinolysis were measured. Plasma levels of free thrombin and APC were higher in the MPN+ than in the MPN− cohort, with 0.49 vs. <0.46 pmol/L (p = 0.0057), respectively, 1.23 vs. 0.58 pmol/L (p = 0.0122), and in healthy controls (vs. <0.46 pmol/L, p = 0.0012; vs. 0.54 pmol/L, p = 0.0035). The indirect activation markers prothrombin fragment 1+2, thrombin-antithrombin complex, and D-dimer did not differ between groups. Receiver operating characteristic analysis suggested that SVT patients with MPN can be better distinguished by APC than by conventional indirect thrombin markers. A potential application of these biomarkers to guide anticoagulant therapy and to investigate the role of the PC pathway in MPN-associated hypercoagulability should be further studied.
Metabolomic and Transcriptomic Analyses of Flavonoid Biosynthesis in Different Colors of Soybean Seed Coats
Authors: Fan Yuanfang , Hussain Sajad , Wang Xianshu , Yang Mei , Zhong Xiaojuan , Tao Lei , Li Jing , Zhou Yonghang , Xiang Chao
Published: December 2024

Soybean has outstanding nutritional and medicinal value because of its abundant protein, oil, and flavonoid contents. This crop has rich seed coat colors, such as yellow, green, black, brown, and red, as well as bicolor variants. However, there are limited reports on the synthesis of flavonoids in the soybean seed coats of different colors. Thus, the seed coat metabolomes and transcriptomes of five soybean germplasms with yellow (S141), red (S26), brown (S62), green (S100), and black (S124) seed coats were measured. In this study, 1645 metabolites were detected in the soybean seed coat, including 426 flavonoid compounds. The flavonoids differed among the different-colored seed coats of soybean germplasms, and flavonoids were distributed in all varieties. Procyanidins A1, B1, B6, C1, and B2, cyanidin 3-O-(6″-malonyl-arabinoside), petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, and malvidin 3-laminaribioside were significantly upregulated in S26_vs._S141, S62_vs._S141, S100_vs._S141, and S124_vs._S141 groups, with a variation of 1.43–2.97 × 1013 in terms of fold. The differences in the contents of cyanidin 3-O-(6″-malonyl-arabinoside) and proanthocyanidin A1 relate to the seed coat color differences of red soybean. Malvidin 3-laminaribioside, petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, cyanidin 3-O-(6″-malonyl-arabinoside), and proanthocyanidin A1 affect the color of black soybean. The difference in the contents of procyanidin B1 and malvidin 3-glucoside-4-vinylphenol might be related to the seed coat color differences of brown soybeans. Cyanidin 3-gentiobioside affects the color of green soybean. The metabolomic–transcriptomic combined analysis showed that flavonoid biosynthesis is the key synthesis pathway for soybean seed color formation. Transcriptome analysis revealed that the upregulation of most flavonoid biosynthesis genes was observed in all groups, except for S62_vs._S141, and promoted flavonoid accumulation. Furthermore, CHS, CHI, DFR, FG3, ANR, FLS, LAR, and UGT88F4 exhibited differential expression in all groups. This study broadens our understanding of the metabolic and transcriptomic changes in soybean seed coats of different colors and provides new insights into developing bioactive substances from soybean seed coats.
Novel KCNQ2 Variants Related to a Variable Phenotypic Spectrum Ranging from Epilepsy with Auditory Features to Severe Developmental and Epileptic Encephalopathies
Authors: Talarico Mariagrazia , Procopio Radha , Gagliardi Monica , Sarubbi Maria Chiara , Fortunato Francesco , Sammarra Ilaria , Lesca Gaetan , Malanga Donatella , Annesi Grazia , Gambardella Antonio
Published: December 2024

Pathogenic KCNQ2 variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to KCNQ2–developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.1378G>A and c.2251T>G) and the already-reported pathogenic splice site (c.1631+1G>A) in KCNQ2 (HGNC:6296). The phenotypes observed in the affected members of family 1, which shared the c.2251T>G variant, were epilepsy with auditory features (EAFs), focal epilepsy, and generalized epilepsy, and none of them suffered from neonatal seizures. The gene panel contained further genes related to EAFs (LGI1, RELN, SCN1A, and DEPDC5), which were tested with negative results. The phenotypes observed in family 2 members, sharing the splice site variant, were neonatal seizures and focal epilepsy in childhood. The last unrelated proband, harboring the de novo missense c.1378G>A, presented a clinical phenotype consistent with DEE. In conclusion, we identified two unreported KCNQ2 variants, and report a proband with EAFs and individuals without typical KCNQ2 neonatal seizures. Our study underscores the extreme variability in the phenotypic spectrum of KCNQ2-related epilepsies and unveils the prospect of its inclusion in screening panels for EAFs.
Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction
Authors: Klabenkova Kristina , Zakhryamina Alyona , Burakova Ekaterina , Bizyaev Sergei , Fokina Alesya , Stetsenko Dmitry
Published: December 2024

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by the chemical modification of the internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previously developed a strategy for the chemical modification of the phosphate group via the Staudinger reaction on a solid phase of the intermediate dinucleoside phosphite triester and a range of, preferably, electron deficient organic azides such as sulfonyl azides during automated solid-phase DNA synthesis according to the conventional β-cyanoethyl phosphoramidite scheme. Polyfluoro compounds are characterized by unique properties that have prompted their extensive application both in industry and in scientific research. We report herein the synthesis and isolation of novel oligodeoxyribonucleotides incorporating internucleotidic perfluoro-1-octanesulfonyl phosphoramidate or 2,2,2-trifluoroethanesulfonyl phosphoramidate groups. In addition, novel oligonucleotide derivatives with fluorinated zwitterionic phosphate mimics were synthesized by a tandem methodology, which involved (a) the introduction of a carboxylic ester group at the internucleotidic position via the Staudinger reaction with methyl 2,2-difluoro-3-azidosulfonylacetate; and (b) treatment with an aliphatic diamine, e.g., 1,1-dimethylethylenediamine or 1,3-diaminopropane. It was further shown that the polyfluoro oligonucleotides obtained were able to form complementary duplexes with either DNA or RNA, which were not significantly differing in stability from the natural counterparts. Long-chain perfluoroalkyl oligonucleotides were taken up into cultured human cells in the absence of a transfection agent. It may be concluded that the polyfluoro oligonucleotides described here can represent a useful platform for designing oligonucleotide therapeutics.
Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis
Authors: Shalaby Carson , Garifallou James , Thom Christopher S.
Published: December 2024

Mammalian blood cells originate from specialized ‘hemogenic’ endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs. We used single cell RNA sequencing analysis from human embryonic cells to identify relevant signaling pathways that support nascent HSC release. In addition to intercellular and secreted signaling modalities that have been previously functionally validated to support EHT and/or developmental hematopoiesis in model systems, we identify several novel modalities with plausible mechanisms to support EHT and HSC release. Our findings paint a portrait of the complex inter-regulated signals from the local niche, circulating hematopoietic/inflammatory cells, and distal fetal liver that support hematopoiesis.
A Pipelined Hardware Design of FNTT and INTT of CRYSTALS-Kyber PQC Algorithm
Authors: Rashid Muhammad , Sonbul Omar S. , Jamal Sajjad Shaukat , Jaffar Amar Y. , Kakhorov Azamat
Published: December 2024

Lattice-based post-quantum cryptography (PQC) algorithms demand number theoretic transform (NTT)-based polynomial multiplications. NTT-based polynomials’ multiplication relies on the computation of forward number theoretic transform (FNTT) and inverse number theoretic transform (INTT), respectively. Therefore, this work presents a unified NTT hardware accelerator architecture to facilitate the polynomial multiplications of the CRYSTALS-Kyber PQC algorithm. Moreover, a unified butterfly unit design of Cooley–Tukey and Gentleman–Sande configurations is proposed to implement the FNTT and INTT operations using one adder, one multiplier, and one subtractor, sharing four routing multiplexers and one Barrett-based modular reduction unit. The critical path of the proposed butterfly unit is minimized using pipelining. An efficient controller is implemented for control functionalities. The simulation results after the post-place and -route step are provided on Xilinx Virtex-6 and Virtex-7 field-programmable gate array devices. Also, the proposed design is physically implemented for validation on Virtex-7 FPGA. The number of slices utilized on Virtex-6 and Virtex-7 devices is 398 and 312, the required number of clock cycles for one set of FNTT and INTT computations is 1410 and 1540, and the maximum operating frequency is 256 and 290 MHz, respectively. The average figure of merit (FoM), where FoM is the ratio of throughput to slices, illustrates 62% better performance than the most relevant NTT design from the literature.
Automatic Detection of Railway Faults Using Neural Networks: A Comparative Study of Transfer Learning Models and YOLOv11
Authors: Rodríguez-Abreo Omar , Quiroz-Juárez Mario A. , Macías-Socarras Idalberto , Rodríguez-Reséndiz Juvenal , Camacho-Pérez Juan M. , Carcedo-Rodríguez Gabriel , Camacho-Pérez Enrique
Published: December 2024

Developing reliable railway fault detection systems is crucial for ensuring both safety and operational efficiency. Various artificial intelligence frameworks, especially deep learning models, have shown significant potential in enhancing fault detection within railway infrastructure. This study explores the application of deep learning models for railway fault detection, focusing on both transfer learning architectures and a novel classification framework. Transfer learning was utilized with architectures such as ResNet50V2, Xception, VGG16, MobileNet, and InceptionV3, which were fine-tuned to classify railway track images into defective and non-defective categories. Additionally, the state-of-the-art YOLOv11 model was adapted for the same classification task, leveraging advanced data augmentation techniques to achieve high accuracy. Among the transfer learning models, VGG16 demonstrated the best performance with a test accuracy of 89.18%. However, YOLOv11 surpassed all models, achieving a test accuracy of 92.64% while maintaining significantly lower computational demands. These findings underscore the versatility of deep learning models and highlight the potential of YOLOv11 as an efficient and accurate solution for railway fault classification tasks.
Unveiling the Potential of Metaheuristics in Transportation: A Path Towards Efficiency, Optimization, and Intelligent Management
Authors: Bueno-Ferrer Álvaro , De Pablo Valenciano Jaime , De Burgos Jiménez Jerónimo
Published: December 2024

Importance: This bibliometric analysis of the application of metaheuristics in transportation and logistics examines over two decades of research (1999–present), aiming to uncover global trends, anticipate future directions, and highlight how interconnections between key factors facilitate the development of practical and sustainable solutions for the industry. Methodology: A quantitative approach is employed to analyze the evolution of the discipline by reviewing an extensive database of relevant research and key authors and utilizing advanced data processing tools. This analysis enables the assessment of advances in the optimization of metaheuristic models, with an impact on time and cost savings from an economically sustainable perspective. Results: The use of metaheuristics optimizes the efficiency and competitiveness of the transportation sector while promoting a positive economic impact on companies. The main areas of application are optimization and metaheuristic methods, cost and operational efficiency, planning and scheduling, logistics and transportation, supply chain and logistics networks, energy and sustainability, and demand and users. Additionally, genetic algorithms stand out as particularly important. Conclusions: This research provides a comprehensive and detailed view of the impact of metaheuristics on the transportation sector, highlighting their current and future trends (such as artificial intelligence) and their economic relevance.
LoRa Technology Enhanced with a Custom-Designed High-Gain Yagi-Uda Antenna for Data Transmission from Misti Volcano Monitoring to Arequipa City
Authors: Arana Medina Flor de Milagro Yesit , Rendulich Jorge
Published: December 2024

This study details the design and implementation of a high-gain Yagi-Uda antenna network for the transmission of real-time monitoring data from the Misti Volcano to the city of Arequipa. As Misti is classified as a high-risk volcano due to its active volcanic nature and the close proximity of nearly one million inhabitants, the current monitoring infrastructure is insufficient to meet the demands of effective surveillance. In response, this project integrates Internet of Things (IoT) technology, the LoRa (Long Range) network, and an optimized seven-element Yagi-Uda antenna, developed using advanced optimization algorithms to enhance transmission efficiency. The primary objective is to facilitate the reliable collection and transmission of critical sensor data for subsequent analysis by volcanological experts, thereby supporting improved prediction and mitigation of potential volcanic hazards. Field tests have demonstrated that the Yagi-Uda antenna, when coupled with LoRa technology, achieved uninterrupted data transmission over a distance of 16 km. The integration of IoT, LoRa, and the optimized antenna design offers a scalable and resilient solution for the continuous monitoring and risk assessment of Misti, enabling the incorporation of advanced high-precision sensors for enhanced surveillance capabilities.