bluuebunny/crossref_metadata_2025 huggingface dataset:
Adhesion of Escherichia coli and Lactobacillus fermentum to Films and Electrospun Fibrous Scaffolds from Composites of Poly(3-hydroxybutyrate) with Magnetic Nanoparticles in a Low-Frequency Magnetic Field
Authors: Voinova Vera V. , Zhuikov Vsevolod A. , Zhuikova Yulia V. , Sorokina Anastasia A. , Makhina Tatiana K. , Bonartseva Garina A. , Parshina Evgeniia Yu. , Hossain Muhammad Asif , Shaitan Konstantin V. , Pryadko Artyom S. , Chernozem Roman V. , Mukhortova Yulia R. , Shlapakova Lada E. , Surmenev Roman A. , Surmeneva Maria A. , Bonartsev Anton P.
Published: December 2023

The ability of materials to adhere bacteria on their surface is one of the most important aspects of their development and application in bioengineering. In this work, the effect of the properties of films and electrospun scaffolds made of composite materials based on biosynthetic poly(3-hydroxybutyrate) (PHB) with the addition of magnetite nanoparticles (MNP) and their complex with graphene oxide (MNP/GO) on the adhesion of E. coli and L. fermentum under the influence of a low-frequency magnetic field and without it was investigated. The physicochemical properties (crystallinity; surface hydrophilicity) of the materials were investigated by X-ray structural analysis, differential scanning calorimetry and “drop deposition” methods, and their surface topography was studied by scanning electron and atomic force microscopy. Crystal violet staining made it possible to reveal differences in the surface charge value and to study the adhesion of bacteria to it. It was shown that the differences in physicochemical properties of materials and the manifestation of magnetoactive properties of materials have a multidirectional effect on the adhesion of model microorganisms. Compared to pure PHB, the adhesion of E. coli to PHB-MNP/GO, and for L. fermentum to both composite materials, was higher. In the magnetic field, the adhesion of E. coli increased markedly compared to PHB-MNP/GO, whereas the effect on the adhesion of L. fermentum was reversed and was only evident in samples with PHB-MNP. Thus, the resultant factors enhancing and impairing the substrate binding of Gram-negative E. coli and Gram-positive L. fermentum turned out to be multidirectional, as they probably have different sensitivity to them. The results obtained will allow for the development of materials with externally controlled adhesion of bacteria to them for biotechnology and medicine.
Antigenic Architecture of the H7N2 Influenza Virus Hemagglutinin Belonging to the North American Lineage
Authors: Lyashko Aleksandr V. , Timofeeva Tatiana A. , Rudneva Irina A. , Lomakina Natalia F. , Treshchalina Anastasia A. , Gambaryan Alexandra S. , Sorokin Evgenii V. , Tsareva Tatiana R. , Adams Simone E. , Prilipov Alexey G. , Sadykova Galina K. , Timofeev Boris I. , Logunov Denis Y. , Gintsburg Alexander L.
Published: December 2023

The North American low pathogenic H7N2 avian influenza A viruses, which lack the 220-loop in the hemagglutinin (HA), possess dual receptor specificity for avian- and human-like receptors. The purpose of this work was to determine which amino acid substitutions in HA affect viral antigenic and phenotypic properties that may be important for virus evolution. By obtaining escape mutants under the immune pressure of treatment with monoclonal antibodies, antigenically important amino acids were determined to be at positions 125, 135, 157, 160, 198, 200, and 275 (H3 numbering). These positions, except 125 and 275, surround the receptor binding site. The substitutions A135S and A135T led to the appearance of an N-glycosylation site at 133N, which reduced affinity for the avian-like receptor analog and weakened binding with tested monoclonal antibodies. Additionally, the A135S substitution is associated with the adaptation of avian viruses to mammals (cat, human, or mouse). The mutation A160V decreased virulence in mice and increased affinity for the human-type receptor analog. Conversely, substitution G198E, in combination with 157N or 160E, displayed reduced affinity for the human-type receptor analog.
Biosynthesis, Engineering, and Delivery of Selenoproteins
Authors: Wright David E. , O’Donoghue Patrick
Published: December 2023

Selenocysteine (Sec) was discovered as the 21st genetically encoded amino acid. In nature, site-directed incorporation of Sec into proteins requires specialized biosynthesis and recoding machinery that evolved distinctly in bacteria compared to archaea and eukaryotes. Many organisms, including higher plants and most fungi, lack the Sec-decoding trait. We review the discovery of Sec and its role in redox enzymes that are essential to human health and important targets in disease. We highlight recent genetic code expansion efforts to engineer site-directed incorporation of Sec in bacteria and yeast. We also review methods to produce selenoproteins with 21 or more amino acids and approaches to delivering recombinant selenoproteins to mammalian cells as new applications for selenoproteins in synthetic biology.
Mitochondrial Reactive Oxygen Species in TRIF-Dependent Toll-like Receptor 3 Signaling in Bronchial Epithelial Cells against Viral Infection
Authors: Chu Ga Eul , Park Jun Young , Park Chan Ho , Cho Won Gil
Published: December 2023

Toll-like receptor 3 (TLR3) plays an important role in double-stranded RNA recognition and triggers the innate immune response by acting as a key receptor against viral infections. Intracellular reactive oxygen species (ROS) are involved in TLR3-induced inflammatory responses during viral infections; however, their relationship with mitochondrial ROS (mtROS) remains largely unknown. In this study, we show that polyinosinic–polycytidylic acid (poly(I:C)), a mimic of viral RNA, induced TLR3-mediated nuclear factor-kappa B (NF-κB) signaling pathway activation and enhanced mtROS generation, leading to inflammatory cytokine production. TLR3-targeted small interfering RNA (siRNA) and Mito-TEMPO inhibited inflammatory cytokine production in poly(I:C)-treated BEAS-2B cells. Poly(I:C) recruited the TLR3 adaptor molecule Toll/IL-1R domain-containing adaptor, inducing IFN (TRIF) and activated NF-κB signaling. Additionally, TLR3-induced mtROS generation suppression and siRNA-mediated TRIF downregulation attenuated mitochondrial antiviral signaling protein (MAVS) degradation. Our findings provide insights into the TLR3-TRIF signaling pathway and MAVS in viral infections, and suggest TLR3-mtROS as a therapeutic target for the treatment of airway inflammatory and viral infectious diseases.
Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients
Authors: Gavriilaki Eleni , Bousiou Zoi , Batsis Ioannis , Vardi Anna , Mallouri Despina , Koravou Evaggelia-Evdoxia , Konstantinidou Georgia , Spyridis Nikolaos , Karavalakis Georgios , Noli Foteini , Patriarcheas Vasileios , Masmanidou Marianna , Touloumenidou Tasoula , Papalexandri Apostolia , Poziopoulos Christos , Yannaki Evangelia , Sakellari Ioanna , Politou Marianna , Papassotiriou Ioannis
Published: December 2023

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) and graft-versus-host disease (GvHD) represent life-threatening syndromes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both conditions, endothelial dysfunction is a common denominator, and development of relevant biomarkers is of high importance for both diagnosis and prognosis. Despite the fact that soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings, their role in HSCT-related complications remains unexplored. In this context, we used immunoenzymatic methods to measure suPAR and GDF-15 levels in HSCT-TMA, acute and/or chronic GVHD, control HSCT recipients, and apparently healthy individuals of similar age and gender. We found considerably greater SuPAR and GDF-15 levels in HSCT-TMA and GVHD patients compared to allo-HSCT and healthy patients. Both GDF-15 and suPAR concentrations were linked to EASIX at day 100 and last follow-up. SuPAR was associated with creatinine and platelets at day 100 and last follow-up, while GDF-15 was associated only with platelets, suggesting that laboratory values do not drive EASIX. SuPAR, but not GDF-15, was related to soluble C5b-9 levels, a sign of increased HSCT-TMA risk. Our study shows for the first time that suPAR and GDF-15 indicate endothelial damage in allo-HSCT recipients. Rigorous validation of these biomarkers in many cohorts may provide utility for their usefulness in identifying and stratifying allo-HSCT recipients with endothelial cell impairment.
The Combination of Bioavailable Concentrations of Curcumin and Resveratrol Shapes Immune Responses While Retaining the Ability to Reduce Cancer Cell Survival
Authors: Focaccetti Chiara , Palumbo Camilla , Benvenuto Monica , Carrano Raffaele , Melaiu Ombretta , Nardozi Daniela , Angiolini Valentina , Lucarini Valeria , Kërpi Bora , Masuelli Laura , Cifaldi Loredana , Bei Roberto
Published: December 2023

The polyphenols Curcumin (CUR) and Resveratrol (RES) are widely described for their antitumoral effects. However, their low bioavailability is a drawback for their use in therapy. The aim of this study was to explore whether CUR and RES, used at a bioavailable concentration, could modulate immune responses while retaining antitumor activity and to determine whether CUR and RES effects on the immune responses of peripheral blood mononuclear cells (PBMCs) and tumor growth inhibition could be improved by their combination. We demonstrate that the low-dose combination of CUR and RES reduced the survival of cancer cell lines but had no effect on the viability of PBMCs. Although following CUR + RES treatment T lymphocytes showed an enhanced activated state, RES counteracted the increased IFN-γ expression induced by CUR in T cells and the polyphenol combination increased IL-10 production by T regulatory cells. On the other hand, the combined treatment enhanced NK cell activity through the up- and downregulation of activating and inhibitory receptors and increased CD68 expression levels on monocytes/macrophages. Overall, our results indicate that the combination of CUR and RES at low doses differentially shapes immune cells while retaining antitumor activity, support the use of this polyphenol combinations in anticancer therapy and suggest its possible application as adjuvant for NK cell-based immunotherapies.
The Roles of Mepiquate Chloride and Melatonin in the Morpho-Physiological Activity of Cotton under Abiotic Stress
Authors: Wu Yanqing , Liu Jiao , Wu Hao , Zhu Yiming , Ahmad Irshad , Zhou Guisheng
Published: December 2023

Cotton growth and yield are severely affected by abiotic stress worldwide. Mepiquate chloride (MC) and melatonin (MT) enhance crop growth and yield by reducing the negative effects of abiotic stress on various crops. Numerous studies have shown the pivotal role of MC and MT in regulating agricultural growth and yield. Nevertheless, an in-depth review of the prominent performance of these two hormones in controlling plant morpho-physiological activity and yield in cotton under abiotic stress still needs to be documented. This review highlights the effects of MC and MT on cotton morpho-physiological and biochemical activities; their biosynthetic, signaling, and transduction pathways; and yield under abiotic stress. Furthermore, we also describe some genes whose expressions are affected by these hormones when cotton plants are exposed to abiotic stress. The present review demonstrates that MC and MT alleviate the negative effects of abiotic stress in cotton and increase yield by improving its morpho-physiological and biochemical activities, such as cell enlargement; net photosynthesis activity; cytokinin contents; and the expression of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase. MT delays the expression of NCED1 and NCED2 genes involved in leaf senescence by decreasing the expression of ABA-biosynthesis genes and increasing the expression of the GhYUC5, GhGA3ox2, and GhIPT2 genes involved in indole-3-acetic acid, gibberellin, and cytokinin biosynthesis. Likewise, MC promotes lateral root formation by activating GA20x genes involved in gibberellin catabolism. Overall, MC and MT improve cotton’s physiological activity and antioxidant capacity and, as a result, improve the ability of the plant to resist abiotic stress. The main purpose of this review is to present an in-depth analysis of the performance of MC and MT under abiotic stress, which might help to better understand how these two hormones regulate cotton growth and productivity.
28S rRNA-Derived Fragments Represent an Independent Molecular Predictor of Short-Term Relapse in Prostate Cancer
Authors: Diamantopoulos Marios A. , Georgoulia Konstantina K. , Levis Panagiotis , Kotronopoulos Georgios , Stravodimos Konstantinos , Kontos Christos K. , Avgeris Margaritis , Scorilas Andreas
Published: December 2023

Prostate cancer (PCa) is a global health concern, being a leading cause of cancer-related mortality among males. Early detection and accurate prognosis are crucial for effective management. This study delves into the diagnostic and prognostic potential of 28S rRNA-derived fragments (rRFs) in PCa. Total RNA extracted from 89 PCa and 53 benign prostate hyperplasia (BPH) tissue specimens. After 3’-end polyadenylation, we performed reverse transcription to create first-strand cDNA. Using an in-house quantitative real-time PCR (qPCR) assay, we quantified 28S rRF levels. Post-treatment biochemical relapse served as the clinical endpoint event for survival analysis, which we validated internally through bootstrap analysis. Our results revealed downregulated 28S rRF levels in PCa compared to BPH patients. Additionally, we observed a significant positive correlation between 28S rRF levels and higher Gleason scores and tumor stages. Furthermore, PCa patients with elevated 28S rRF expression had a significantly higher risk of post-treatment disease relapse independently of clinicopathological data. In conclusion, our study demonstrates, for the first time, the prognostic value of 28S rRF in prostate adenocarcinoma. Elevated 28S rRF levels independently predict short-term PCa relapse and enhance risk stratification. This establishes 28S rRF as a potential novel molecular marker for PCa prognosis.
Role of Sox3 in Estradiol-Induced Sex Reversal in Pelodiscus sinensis
Authors: Zhou Tong , Cao Jizeng , Chen Guobin , Wang Yubin , Zou Guiwei , Liang Hongwei
Published: December 2023

The Chinese soft-shelled turtle Pelodiscus sinensis, an economically important species in China, exhibits significant sexual dimorphism. Males are more valuable than females owing to their wider calipash and faster growth. Estradiol (E2)-induced sex reversal is used to achieve all-male breeding of turtles; however, the mechanism of this sex reversal remains unclear. In this study, we characterized the Sox3 gene, whose expression level was high in the gonads and brain and exhibited significant sexual dimorphism in the ovary. During embryonic development, Sox3 was highly expressed at the initiation of ovarian differentiation. E2 and Sox3-RNAi treatment before sexual differentiation led to 1352, 908, 990, 1011, and 975 differentially expressed genes in five developmental stages, respectively, compared with only E2 treatment. The differentially expressed genes were clustered into 20 classes. The continuously downregulated and upregulated genes during gonadal differentiation were categorized into Class 0 (n = 271) and Class 19 (n = 606), respectively. KEGG enrichment analysis showed that Sox3 significantly affected sexual differentiation via the Wnt, TGF-β, and TNF signaling pathways and mRNA surveillance pathway. The expression of genes involved in these signaling pathways, such as Dkk4, Nog, Msi1, and Krt14, changed significantly during gonadal differentiation. In conclusion, the deletion of Sox3 may lead to significant upregulation of the mRNA surveillance pathway and TNF and Ras signaling pathways and downregulation of the Wnt and TGF-β signaling pathways, inhibiting E2-induced sex reversal. These findings suggest that Sox3 may play a certain promoting effect during E2-induced sex reversal in P. sinensis.
Whispers in the Blood: Leveraging MicroRNAs for Unveiling Autologous Blood Doping in Athletes
Authors: Hassanpour Mehdi , Salybekov Amankeldi A.
Published: December 2023

The prevalence of autologous blood transfusions (ABTs) presents a formidable challenge in maintaining fair competition in sports, as it significantly enhances hemoglobin mass and oxygen capacity. In recognizing ABT as a prohibited form of doping, the World Anti-Doping Agency (WADA) mandates stringent detection methodologies. While current methods effectively identify homologous erythrocyte transfusions, a critical gap persists in detecting autologous transfusions. The gold standard practice of longitudinally monitoring hematological markers exhibits promise but is encumbered by limitations. Despite its potential, instances of blood doping often go undetected due to the absence of definitive verification processes. Moreover, some cases remain unpenalized due to conservative athlete-sanctioning approaches. This gap underscores the imperative need for a more reliable and comprehensive detection method capable of unequivocally differentiating autologous transfusions, addressing the challenges faced in accurately identifying such prohibited practices. The development of an advanced detection methodology is crucial to uphold the integrity of anti-doping measures, effectively identifying and penalizing instances of autologous blood transfusion. This, in turn, safeguards the fairness and equality essential to competitive sports. Our review tackles this critical gap by harnessing the potential of microRNAs in ABT doping detection. We aim to summarize alterations in the total microRNA profiles of erythrocyte concentrates during storage and explore the viability of observing these changes post-transfusion. This innovative approach opens avenues for anti-doping technologies and commercialization, positioning it as a cornerstone in the ongoing fight against doping in sports and beyond. The significance of developing a robust detection method cannot be overstated, as it ensures the credibility of anti-doping efforts and promotes a level playing field for all athletes.
Resources for Human Health from the Plant Kingdom: The Potential Role of the Flavonoid Apigenin in Cancer Counteraction
Authors: Fossatelli Laura , Maroccia Zaira , Fiorentini Carla , Bonucci Massimo
Published: December 2023

Apigenin is one of the most widespread flavonoids in the plant kingdom. For centuries, apigenin-containing plant preparations have been used in traditional medicines to treat diseases that have an inflammatory and/or degenerative component. In the 1980s, apigenin was proposed to interfere with the process of carcinogenesis. Since then, more and more evidence has demonstrated its anticancer efficacy, both in vitro and in vivo. Apigenin has been shown to target signaling pathways involved in the development and progression of cancer, such as PI3K/Akt/mTOR, MAPK/ERK, JAK/STAT, NF-κB, and Wnt/β-catenin pathways, and to modulate different hallmarks of cancer, such as cell proliferation, metastasis, apoptosis, invasion, and cell migration. Furthermore, apigenin modulates PD1/PD-L1 expression in cancer/T killer cells and regulates the percentage of T killer and T regulatory cells. Recently, apigenin has been studied for its synergic and additive effects when combined with chemotherapy, minimizing the side effects. Unfortunately, its low bioavailability and high permeability limit its therapeutic applications. Based on micro- and nanoformulations that enhance the physical stability and drug-loading capacity of apigenin and increase the bioavailability of apigenin, novel drug-delivery systems have been investigated to improve its solubility.
Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine
Authors: Rodríguez-Domínguez Maria Carla , Montes-de-Oca-Jiménez Roberto , Vázquez-Chagoyán Juan Carlos , Rivadeneira-Barreiro Pilar Eliana , Zambrano-Rodríguez Pablo Cleomenes , Ruiz-Riva-Palacio Martha Elba , Gutiérrez-Castillo Adriana del Carmen , de-Castro-Soares Siomar , Vieyra-Reyes Patricia , Arteaga-Troncoso Gabriel
Published: December 2023

Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.
Tryptophan Metabolism in Postmenopausal Women with Functional Constipation
Authors: Blonska Aleksandra , Chojnacki Marcin , Macieja Anna , Blasiak Janusz , Majsterek Ireneusz , Chojnacki Jan , Poplawski Tomasz
Published: December 2023

Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal symptoms (Rome IV) in postmenopausal women with functional constipation (FC, n = 40) as compared with age-adjusted postmenopausal women without FC. All women controlled their TRP intake in their daily diet. Urinary levels of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (indican, 3-IS), were determined by liquid chromatography/tandem mass spectrometry. Dysbiosis was assessed by a hydrogen–methane breath test. Women with FC consumed less TRP and had a lower urinary level of 5-HIAA, but higher levels of KYN and 3-IS compared with controls. The severity of symptoms showed a negative correlation with the 5-HIAA level, and a positive correlation with the 3-IS level. In conclusion, changes in TRP metabolism may contribute to FC in postmenopausal women, and dysbiosis may underlie this contribution.
Overdue Calcium Oscillation Causes Polyspermy but Possibly Permits Normal Development in Mouse Eggs
Authors: Fukuoka Mio , Kang Woojin , Katano Daiki , Horiike Sae , Miyado Mami , Tanaka Mamoru , Miyado Kenji , Yamada Mitsutoshi
Published: December 2023

In some non-mammalian eggs, the fusion of one egg and multiple sperm (polyspermy) induces a robust rise in intracellular calcium ion (Ca2+) concentration due to a shortage of inducers carried by a single sperm. Instead, one of the sperm nuclei is selected inside the egg for normal embryogenesis. Polyspermy also occurs during the in vitro fertilization of human eggs; however, the fate of such eggs is still under debate. Hence, the relationship between polyspermy and repetitive Ca2+ increases (Ca2+ oscillation) in mammals remains unknown. To address this issue, we used mouse sperm lacking extramitochondrial citrate synthase (eCS), which functions as a Ca2+ oscillation inducer; its lack causes retarded Ca2+ oscillation initiation (eCs-KO sperm). Elevated sperm concentrations normalize Ca2+ oscillation initiation. As expected, eCS deficiency enhanced polyspermy in both zona pellucida (ZP)-free and ZP-intact eggs despite producing the next generation of eCs-KO males. In conclusion, similarly to non-mammalian eggs, mouse eggs may develop normally under polyspermy conditions caused by problematic Ca2+ oscillation.
Balance between Pro- and Antifibrotic Proteins in Mesenchymal Stromal Cell Secretome Fractions Revealed by Proteome and Cell Subpopulation Analysis
Authors: Kulebyakina Maria , Basalova Nataliya , Butuzova Daria , Arbatsky Mikhail , Chechekhin Vadim , Kalinina Natalia , Tyurin-Kuzmin Pyotr , Kulebyakin Konstantin , Klychnikov Oleg , Efimenko Anastasia
Published: December 2023

Multipotent mesenchymal stromal cells (MSCs) regulate tissue repair through paracrine activity, with secreted proteins being significant contributors. Human tissue repair commonly results in fibrosis, where fibroblast differentiation into myofibroblasts is a major cellular mechanism. MSCs’ paracrine activity can inhibit fibrosis development. We previously demonstrated that the separation of MSC secretome, represented by conditioned medium (CM), into subfractions enriched with extracellular vesicles (EV) or soluble factors (SF) boosts EV and SF antifibrotic effect. This effect is realized through the inhibition of fibroblast-to-myofibroblast differentiation in vitro. To unravel the mechanisms of MSC paracrine effects on fibroblast differentiation, we performed a comparative proteomic analysis of MSC secretome fractions. We found that CM was enriched in NF-κB activators and confirmed via qPCR that CM, but not EV or SF, upregulated NF-κB target genes (COX2, IL6, etc.) in human dermal fibroblasts. Furthermore, we revealed that EV and SF were enriched in TGF-β, Notch, IGF, and Wnt pathway regulators. According to scRNAseq, 11 out of 13 corresponding genes were upregulated in a minor MSC subpopulation disappearing in profibrotic conditions. Thus, protein enrichment of MSC secretome fractions and cellular subpopulation patterns shift the balance in fibroblast-to-myofibroblast differentiation, which should be considered in studies of MSC paracrine effects and the therapeutic use of MSC secretome.
Transcriptomic and Metabolomic Profiling Reveals the Variations in Carbohydrate Metabolism between Two Blueberry Cultivars
Authors: Yang Haiyan , Wei Zhiwen , Wu Yaqiong , Zhang Chunhong , Lyu Lianfei , Wu Wenlong , Li Weilin
Published: December 2023

Blueberry is a high-quality fruit tree with significant nutritional and economic value, but the intricate mechanism of sugar accumulation in its fruit remains unclear. In this study, the ripe fruits of blueberry cultivars ‘Anna’ and ‘Misty’ were utilized as experimental materials, and physiological and multi-omics methodologies were applied to analyze the regulatory mechanisms of the difference in sugar content between them. The results demonstrated that the ‘Anna’ fruit was smaller and had less hardness than the ‘Misty’ fruit, as well as higher sugar content, antioxidant capability, and lower active substance content. A total of 7067 differentially expressed genes (DEGs) (3674 up-regulated and 3393 down-regulated) and 140 differentially abundant metabolites (DAMs) (82 up-regulated and 58 down-regulated) were identified between the fruits of the two cultivars. According to KEGG analysis, DEGs were primarily abundant in phenylpropanoid synthesis and hormone signal transduction pathways, whereas DAMs were primarily enriched in ascorbate and aldarate metabolism, phenylpropanoid biosynthesis, and the pentose phosphate pathway. A combined multi-omics study showed that 116 DEGs and 3 DAMs in starch and sucrose metabolism (48 DEGs and 1 DAM), glycolysis and gluconeogenesis (54 DEGs and 1 DAM), and the pentose phosphate pathway (14 DEGs and 1 DAM) were significantly enriched. These findings suggest that blueberries predominantly increase sugar accumulation by activating carbon metabolism network pathways. Moreover, we identified critical transcription factors linked to the sugar response. This study presents new understandings regarding the molecular mechanisms underlying blueberry sugar accumulation and will be helpful in improving blueberry fruit quality through breeding.
Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer
Authors: Bala Vanessa-Meletia , Lampropoulou Dimitra Ioanna , Grammatikaki Stamatiki , Kouloulias Vassilios , Lagopati Nefeli , Aravantinos Gerasimos , Gazouli Maria
Published: December 2023

Hyperthermia has the potential to damage cancerous tissue by increasing the body temperature. However, targeting cancer cells whilst protecting the surrounding tissues is often challenging, especially when implemented in clinical practice. In this direction, there are data showing that the combination of nanotechnology and hyperthermia offers more successful penetration of nanoparticles in the tumor environment, thus allowing targeted hyperthermia in the region of interest. At the same time, unlike radiotherapy, the use of non-ionizing radiation makes hyperthermia an attractive therapeutic option. This review summarizes the existing literature regarding the use of hyperthermia and nanoparticles in cancer, with a focus on nanoparticle-induced cytotoxicity mechanisms.
Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function
Authors: Di Nisio Andrea , De Toni Luca , Sabovic Iva , Vignoli Alessia , Tenori Leonardo , Dall’Acqua Stefano , Sut Stefania , La Vignera Sandro , Condorelli Rosita Angela , Giacone Filippo , Ferlin Alberto , Foresta Carlo , Garolla Andrea
Published: December 2023

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.
Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach
Authors: Cantley Nathan W. P. , Barski Robert , Kemp Helena , Hogg Sarah L. , Wu Hoi Yee Teresa , Bowron Ann , Collingwood Catherine , Cundick Jennifer , Hart Claire , Shakespeare Lynette , Preece Mary Anne , Aitkenhead Helen , Smith Sarah , Carling Rachel S. , Moat Stuart J.
Published: December 2023

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020. Cases of CG diagnosed were determined if detected clinically, NBS, or by family screening, as well as age at diagnosis. Cases referred via the ODS pathway were also collated, including the final diagnosis made. Responses were obtained from 13/16 laboratories. Between 2010 and 2020, a total of 6,642,787 babies were screened, and 172 cases of CG were identified. It should be noted that 85/172 presented clinically, 52/172 were identified by NBS, and 17/172 came from family screening. A total of 117 referrals were made via the ODS pathway, and 45/117 were subsequently diagnosed with CG. Median (interquartile range) age at diagnosis by NBS and clinically was 8 days (7–11) and 10 days (7–16), respectively (Mann–Whitney U test, U = 836.5, p-value = 0.082). The incidence of CG is 1:38,621 live births. The incidence of CG in the UK is comparable with that of other European/western countries. No statistical difference was seen in the timing of diagnosis between NBS and clinical presentation based on the current practice of sampling on day 5. Bringing forward the day of NBS sampling to day 3 would increase the proportion diagnosed with CG by NBS from 52/172 (30.2%) to 66/172 (38.4%).
A Review of Imaging Methods and Recent Nanoparticles for Breast Cancer Diagnosis
Authors: Aminolroayaei Fahimeh , Shahbazi-Gahrouei Saghar , Khorasani Amir , Shahbazi-Gahrouei Daryoush
Published: December 2023

Breast cancer is the foremost common cause of death in women, and its early diagnosis will help treat and increase patients’ survival. This review article aims to look at the studies on the recent findings of standard imaging techniques and their characteristics for breast cancer diagnosis as well as on the recent role of nanoparticles (NPs) that are used for breast cancer detection. Herein, a search was performed in the literature through scientific citation websites, including Google Scholar, PubMed, Scopus, and Web of Science, until May 2023. A comprehensive review of different imaging modalities and NPs for breast cancer diagnosis is given, and the successes, challenges, and limitations of these methods are discussed.
Temporal Development GAN (TD-GAN): Crafting More Accurate Image Sequences of Biological Development
Authors: Celard Pedro , Seara Vieira Adrián , Sorribes-Fdez José Manuel , Iglesias Eva Lorenzo , Borrajo Lourdes
Published: December 2023

In this study, we propose a novel Temporal Development Generative Adversarial Network (TD-GAN) for the generation and analysis of videos, with a particular focus on biological and medical applications. Inspired by Progressive Growing GAN (PG-GAN) and Temporal GAN (T-GAN), our approach employs multiple discriminators to analyze generated videos at different resolutions and approaches. A new Temporal Discriminator (TD) that evaluates the developmental coherence of video content is introduced, ensuring that the generated image sequences follow a realistic order of stages. The proposed TD-GAN is evaluated on three datasets: Mold, Yeast, and Embryo, each with unique characteristics. Multiple evaluation metrics are used to comprehensively assess the generated videos, including the Fréchet Inception Distance (FID), Frechet Video Distance (FVD), class accuracy, order accuracy, and Mean Squared Error (MSE). Results indicate that TD-GAN significantly improves FVD scores, demonstrating its effectiveness in generating more coherent videos. It achieves competitive FID scores, particularly when selecting the appropriate number of classes for each dataset and resolution. Additionally, TD-GAN enhances class accuracy, order accuracy, and reduces MSE compared to the default model, demonstrating its ability to generate more realistic and coherent video sequences. Furthermore, our analysis of stage distribution in the generated videos shows that TD-GAN produces videos that closely match the real datasets, offering promising potential for generating and analyzing videos in different domains, including biology and medicine.
Magnetic Anisotropy Tailoring by 5d-Doping in (Fe,Co)5SiB2 Alloys
Authors: Benea Diana
Published: December 2023

Band-structure calculations were performed using the spin-polarized relativistic Korringa–Kohn–Rostoker (SPR-KKR) band-structure method, determining intrinsic magnetic properties, such as magnetic moments, magnetocrystalline anisotropy energy (MAE), and Curie temperatures, of Fe5−x−yCoxMySiB2 (M = Re, W) alloys. The general gradient approximation (GGA) for the exchange–correlation potential and the atomic sphere approximation (ASA) were used in the calculations. Previous studies have shown that for Fe5SiB2, the easy magnetization direction is in-plane, but it turns axial for Co-doping in the range 1 < x ≤ 2.5 (y = 0). Furthermore, studies have shown that 5d-doping enhances the MAE by enabling the strong spin–orbit coupling of Fe–3d and M–5d states. The aim of the present theoretical calculations was to find the dependence of the anisotropy constant K1 for combined Co- and M-doping, building a two-dimensional (2D) map of K1 for 0 ≤ x ≤ 2 and 0 ≤ y ≤ 1. Similar theoretical 2D maps for magnetization and Curie temperature vs. Co and M content (M = W and Re) were built, allowing for the selection of alloy compositions with enhanced values of uniaxial anisotropy, magnetization, and Curie temperature. The magnetic properties of the Fe4.1W0.9SiB2 alloy that meet the selection criteria for axial anisotropy K1 > 0.2 meV/f.u., Curie temperature Tc > 800 K determined by the mean-field approach, and magnetization µ0Ms > 1 T are discussed.
Metal Rich Metallaboranes: Synthesis, Structure and Bonding of pileo-[(Cp*Ru)2M(CO)3(µ-H)(µ-E)(µ3-BH)B2H5] (M = Mo, W, E = CO, and M = Mn, E = H) Clusters
Authors: Pradhan Alaka Nanda , Jaiswal Shippy , Cordier Marie , Halet Jean-François , Ghosh Sundargopal
Published: December 2023

The synthesis and structural characterization of a series of heterotrimetallic ruthenaborane clusters are reported. The photolytic reaction of nido-[(Cp*Ru)2(µ-H)2B3H7] (nido-1) (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl) with [M(CO)5·THF] (THF = tetrahydrofuran, M = Mo and W) yielded the heterotrimetallic clusters pileo-[(Cp*Ru)2{M(CO)3}(µ-CO)(µ-H)(µ3-BH)B2H5], M = Mo (2), W (3) and the known arachno ruthenaboranes [1,2-(Cp*Ru)(Cp*RuCO)(µ-H)B3H8] (I) and [{Cp*Ru(CO)}2B2H6] (II). In an attempt to synthesize the Mn-analog of 2 and 3, we performed a similar reaction of nido-1 with [Mn2(CO)10], which afforded the heterotrimetallic pileo-[(Cp*Ru){Mn(CO)3}(µ-H)2(µ3-BH)B2H5] (4) cluster along with the reported trimetallic hydrido(hydroborylene) species [(Cp*Ru)2{Mn(CO)3}(µ-H)(µ-CO)3(µ-BH)] (III). Ruthenaboranes 2, 3 and 4 are isoelectronic and isostructural. The geometry of 2–4 can be viewed as a triangle face-fused square pyramidal and tetrahedral geometry, in which the apical vertex of the tetrahedron is occupied by a µ3–BH moiety. All of these pileo ruthenaborane clusters obey Mingos’ fusion formalism. Clusters 2–4 were characterized using multinuclear NMR, IR spectroscopies and electrospray ionization mass spectrometry. The single-crystal X-ray diffraction studies of clusters 2 and 4 confirmed their structures. Further, density functional theory (DFT) studies of these pileo ruthenaboranes have been carried out to investigate the nature of bonding, fusion and electronic structures.
Ixodes scapularis Is the Most Susceptible of the Three Canonical Human-Biting Tick Species of North America to Repellent and Acaricidal Effects of the Natural Sesquiterpene, (+)-Nootkatone
Authors: Siegel Eric L. , Xu Guang , Li Andrew Y. , Pearson Patrick , D’hers Sebastián , Elman Noel , Mather Thomas N. , Rich Stephen M.
Published: December 2023

Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC50) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC50 = 0.87 ± 0.05 µg/cm2). Higher concentrations were required to repel D. variabilis (EC50 = 252 ± 12 µg/cm2) and A. americanum (EC50 = 2313 ± 179 µg/cm2). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues.
An Overview of Mathematical Methods Applied in the Biomechanics of Foot and Ankle–Foot Orthosis Models
Authors: Nazha Hasan Mhd , Szávai Szabolcs , Juhre Daniel
Published: December 2023

Ankle–foot orthoses (AFOs) constitute medical instruments designed for patients exhibiting pathological gait patterns, notably stemming from conditions such as stroke, with the primary objective of providing support and facilitating rehabilitation. The present research endeavors to conduct a comprehensive review of extant scholarly literature focusing on mathematical techniques employed for the examination of AFO models. The overarching aim is to gain deeper insights into the biomechanical intricacies underlying these ankle–foot orthosis models from a mathematical perspective, while concurrently aiming to advance novel models within the domain. Utilizing a specified set of keywords and their configurations, a systematic search was conducted across notable academic databases, including ISI Web of Knowledge, Google Scholar, Scopus, and PubMed. Subsequently, a total of 23 articles were meticulously selected for in-depth review. These scholarly contributions collectively shed light on the utilization of nonlinear optimization techniques within the context of ankle–foot orthoses (AFOs), specifically within the framework of fully Cartesian coordinates, encompassing both kinematic and dynamic dimensions. Furthermore, an exploration of a two-degree-of-freedom AFO design tailored for robotic rehabilitation, which takes into account the interplay between foot and orthosis models, is delineated. Notably, the review article underscores the incorporation of shape memory alloy (SMA) elements in AFOs and overviews the constitutive elastic, viscoelastic, and hyperelastic models. This comprehensive synthesis of research findings stands to provide valuable insights for orthotists and engineers, enabling them to gain a mathematical understanding of the biomechanical principles underpinning AFO models and fostering the development of innovative AFO designs.
Calciprotein Particles Induce Cellular Compartment-Specific Proteome Alterations in Human Arterial Endothelial Cells
Authors: Shishkova Daria , Lobov Arseniy , Repkin Egor , Markova Victoria , Markova Yulia , Sinitskaya Anna , Sinitsky Maxim , Kondratiev Egor , Torgunakova Evgenia , Kutikhin Anton
Published: December 2023

Calciprotein particles (CPPs) are indispensable scavengers of excessive Ca2+ and PO43− ions in blood, being internalised and recycled by liver and spleen macrophages, monocytes, and endothelial cells (ECs). Here, we performed a pathway enrichment analysis of cellular compartment-specific proteomes in primary human coronary artery ECs (HCAEC) and human internal thoracic artery ECs (HITAEC) treated with primary (amorphous) or secondary (crystalline) CPPs (CPP-P and CPPs, respectively). Exposure to CPP-P and CPP-S induced notable upregulation of: (1) cytokine- and chemokine-mediated signaling, Ca2+-dependent events, and apoptosis in cytosolic and nuclear proteomes; (2) H+ and Ca2+ transmembrane transport, generation of reactive oxygen species, mitochondrial outer membrane permeabilisation, and intrinsic apoptosis in the mitochondrial proteome; (3) oxidative, calcium, and endoplasmic reticulum (ER) stress, unfolded protein binding, and apoptosis in the ER proteome. In contrast, transcription, post-transcriptional regulation, translation, cell cycle, and cell–cell adhesion pathways were underrepresented in cytosol and nuclear compartments, whilst biosynthesis of amino acids, mitochondrial translation, fatty acid oxidation, pyruvate dehydrogenase activity, and energy generation were downregulated in the mitochondrial proteome of CPP-treated ECs. Differentially expressed organelle-specific pathways were coherent in HCAEC and HITAEC and between ECs treated with CPP-P or CPP-S. Proteomic analysis of mitochondrial and nuclear lysates from CPP-treated ECs confirmed bioinformatic filtration findings.
Nicotine Potentially Alters Endothelial Inflammation and Cell Adhesion via LGALS9
Authors: Braß Sönke Maximilian , Mazrekaj Agnesa , Mulorz Joscha , Ibing Wiebke , Krott Kim-Jürgen , Takeuchi Kiku , Cappallo Melanie , Liu Hsiang-Han , Elvers Margitta , Schelzig Hubert , Wagenhäuser Markus Udo
Published: December 2023

Background: The endothelial cell layer is essential for the maintenance of various blood vessel functions. Major risk factors for endothelial dysfunction that contribute to aortic pathologies such as abdominal aortic aneurysm (AAA) and aortic dissection (AD) include smoking tobacco cigarettes and hypertension. This study explores the effects of nicotine (Nic) and angiotensin II (Ang II) on human aortic endothelial cells (HAoECs) at a transcriptional level. Methods: HAoECs were exposed to 100 nM Nic and/or 100 nM Ang II. RNA sequencing (RNA-Seq) was performed to identify regulated genes following exposure. Results were validated applying RT-qPCR. GeneMANIA was used to perform in silico analysis aiming to identify potential downstream interacting genes in inflammatory, cell-adhesion, endothelial cell proliferation, and coagulation pathways. Results: RNA-Seq identified LGALS9 (Galectin-9) as being potentially regulated following Nic exposure, while subsequent RT-qPCR experiments confirmed the transcriptional regulation (p < 0.05). Subsequent in silico analysis identified potential candidate genes for interacting with LGALS9 in different gene sets. Of the top 100 genes potentially interacting with LGALS9, 18 were inflammatory response genes, 28 were involved in cell adhesion, 2 in cell proliferation, and 6 in coagulation. Conclusion: Nic exposure of HAoECs causes a significant increase in LGALS9 at a transcriptional level. LGALS9 itself may serve as key regulator for essential endothelial cell processes via interfering with various signaling pathways and may thus represent a potentially novel target in the pathogenesis of aortic pathologies.