bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological Responses of Pak Choi (Brassica rapa Subsp. Chinensis) Genotypes to Salt Tolerance
Authors: Park Han-kyeol , Kim Si-Hong , Lee Joo-Hwan , Kim Kyeong-Yeon , Sim Jeong-Eun , Jang Dong-Cheol , Park Sung-Min
Published: October 2023

Salinity stress poses a significant challenge to Pak Choi (Brassica rapa subsp. Chinensis) production. To address this limitation, we conducted an evaluation of 24 Korean native Pak Choi species to identify genotypes with resistance to salt stress. Through cluster analysis of electrolyte leakage data, we discovered ‘IT262109’, ‘IT279432’, and ‘IT185735’ as native accessions displaying the strongest salt tolerance. Additionally, our assessment of the maximum quantum yield of photosystem II revealed a 3.7% reduction in seaweed yield in the highly salt-tolerant system compared with the control group, while the weak salt-tolerant system experienced a substantial reduction rate of 45.7% to 49.4%. Notably, salt stress had a significant impact on Pak Choi growth, but the salt-tolerant genotype exhibited less growth reduction compared with the salt-sensitive genotype. Based on the electrolyte leakage and maximum quantum yield data, it was evident that ‘IT185735’ demonstrated poorer growth compared with ‘IT262109’ and ‘IT279432’. Consequently, ‘IT262109’ and ‘IT279432’ show great potential as parent varieties for enhancing salt tolerance in Pak Choi.
Research Progress of Arbuscular Mycorrhizal Fungi Promoting Citrus Growth
Authors: Tang Chungui , Zhang Zhongfeng , Yu Limin , Li Ying
Published: October 2023

Citrus, the world’s most common fruit, boasts an abundance of resources and varieties and possesses a high commodity value. Arbuscular mycorrhizal fungi (AMF) and citrus roots can form a symbiotic relationship, promoting citrus growth, improving its disease resistance, and increasing the quality of the fruits. However, the literature lacks a detailed understanding of the symbiotic citrus–AMF relationship in cultivation. In this study, we reviewed the diversity (different citrus species and habitats), stress resistance (disease, drought, saline-alkali, temperature stresses), expression of defense genes, and underlying mechanisms of symbiotic AMF in citrus. Our aim was to provide a robust reference point and offer valuable insights to guide future studies on citrus symbiotic AMF and their applications in citrus planting. This review could help to facilitate AMF applications in citrus biological control (particularly in the citrus Huanglongbing) and sustainable development.
Phytochemical Profile and Biological Activities of Extracts Obtained from Young Shoots of Blackcurrant (Ribes nigrum L.), European Blueberry (Vaccinium myrtillus L.), and Mountain Cranberry (Vaccinium vitis-idaea L.)
Authors: Solcan Maria-Beatrice , Fizeșan Ionel , Vlase Laurian , Vlase Ana-Maria , Rusu Marius Emil , Mateș Letiția , Petru Andreea-Elena , Creștin Ionuț-Valentin , Tomuțǎ Ioan , Popa Daniela-Saveta
Published: October 2023

This study explores the bioactive potential of young shoots from blackcurrant, European blueberry, and mountain cranberry, widely employed in gemmotherapy and phytotherapy, as rich sources of antioxidants, antimicrobial agents, and anti-inflammatory components. The primary aims of this study were to enhance the extraction conditions for bioactive compounds from blackcurrant young shoots using Modde software for experimental design, to conduct a comprehensive phytochemical analysis of blackcurrant, European blueberry, and mountain cranberry young shoot extracts through LC–MS analysis, and to evaluate the in vitro biological activities of these optimized extracts. The experimental design comprised multiple variables: extraction techniques, solvent type, extraction time, apparent pH, and the solvent-to-vegetal product ratio. The responses included total phenolic content, total flavonoid content, condensed tannin content, and total antioxidant activity determined through the DPPH assay. Furthermore, the antioxidant potential of the extracts was validated through in vitro cell culture experiments, in addition to the cytotoxicity assessments conducted on both normal and cancer cell lines. Extracts obtained through Ultra-Turrax extraction using 70% acetone displayed high levels of polyphenolic compounds and enhanced antioxidant potential, regardless of young shoots origin. LC–MS analysis revealed the predominant occurrence of chlorogenic acid, hyperoside, and isoquercitrin in all examined samples. The optimized extracts also displayed significant biological potential when evaluated in vitro on cell lines. These results provide valuable insights into the potent bioactive components present in these young shoot extracts, paving the way for further exploration in therapeutic applications.
GIS-Based Multi-Criteria Evaluation (MCE) Methods for Aquaculture Site Selection: A Systematic Review and Meta-Analysis
Authors: Chentouf Sanae , Sebbah Boutaina , Bahousse El Houssine , Wahbi Miriam , Maâtouk Mustapha
Published: October 2023

With the growing demand for aquatic products, aquaculture has become a prominent means of meeting this demand. However, the selection of suitable sites for aquaculture remains a key factor in the success of any aquaculture operation. While various methods exist for site selection, geographic information system (GIS)-based multi-criteria evaluation (MCE) methods have emerged as the most widely utilized approach to identifying potential aquaculture sites. Following the guidelines of the preferred reporting items for systematic reviews and meta-analyses (PRISMA), this paper presents a systematic review and meta-analysis of GIS-based MCE methods used in aquaculture sites selection. The objective of this study is to offer a comprehensive overview of existing research in this field and develop a general model for selecting sites for fish and shellfish aquaculture. The main findings indicate a growing number of studies utilizing GIS-based MCE in aquaculture site selection in recent years, with Asia being the leading continent in terms of publications in this domain. Among the journals publishing in this field, the Aquaculture journal stands out as the top publisher. Using consistent criteria across the reviewed studies, two models have been generated, each consisting of four sub-models: water quality, soil quality, infrastructure, and socioeconomic factors; and topography, environment, and physical parameters. These models can aid future researchers and assist decision-makers in identifying optimal locations for aquaculture development.
Mixed Connective Tissue Disease as Different Entity: Global Methylation Aspect
Authors: Filipowicz Gabriela , Wajda Anna , Stypińska Barbara , Kmiołek Tomasz , Felis-Giemza Anna , Stańczyk Sandra , Czuszyńska Zenobia , Walczyk Marcela , Olesińska Marzena , Paradowska-Gorycka Agnieszka
Published: October 2023

Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.
Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities
Authors: Bogut Ana , Stojanovic Bojan , Jovanovic Marina , Dimitrijevic Stojanovic Milica , Gajovic Nevena , Stojanovic Bojana S. , Balovic Goran , Jovanovic Milan , Lazovic Aleksandar , Mirovic Milos , Jurisevic Milena , Jovanovic Ivan , Mladenovic Violeta
Published: October 2023

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, with a complex interplay of molecular pathways contributing to its aggressive nature. Galectin-1 (Gal-1), a member of the galectin family, has emerged as a pivotal player in the PDAC microenvironment, influencing various aspects from tumor growth and angiogenesis to immune modulation. This review provides a comprehensive overview of the multifaceted role of Galectin-1 in PDAC. We delve into its contributions to tumor stroma remodeling, angiogenesis, metabolic reprogramming, and potential implications for therapeutic interventions. The challenges associated with targeting Gal-1 are discussed, given its pleiotropic functions and complexities in different cellular conditions. Additionally, the promising prospects of Gal-1 inhibition, including the utilization of nanotechnology and theranostics, are highlighted. By integrating recent findings and shedding light on the intricacies of Gal-1’s involvement in PDAC, this review aims to provide insights that could guide future research and therapeutic strategies.
A Potential Partnership between Genetics and the Oral Microbiome in Children Displaying Periodic Fever/Aphthosis/Pharyngitis/Adenitis Syndrome
Authors: Rigante Donato , Calò Lea , Ciavarro Alessandro , Galli Jacopo
Published: October 2023

Periodic fever/aphthosis/pharyngitis/adenitis (PFAPA) syndrome was initially described in a small cohort of American children [...]
Simultaneous Promotion of Salt Tolerance and Phenolic Acid Biosynthesis in Salvia miltiorrhiza via Overexpression of Arabidopsis MYB12
Authors: Li Tianyu , Zhang Shuangshuang , Li Yidan , Zhang Lipeng , Song Wenqin , Chen Chengbin , Ruan Weibin
Published: October 2023

Transcription factors play crucial roles in regulating plant abiotic stress responses and physiological metabolic processes, which can be used for plant molecular breeding. In this study, an R2R3-MYB transcription factor gene, AtMYB12, was isolated from Arabidopsis thaliana and introduced into Salvia miltiorrhiza under the regulation of the CaMV35S promoter. The ectopic expression of AtMYB12 resulted in improved salt tolerance in S. miltiorrhiza; transgenic plants showed a more resistant phenotype under high-salinity conditions. Physiological experiments showed that transgenic plants exhibited higher chlorophyll contents, and decreased electrolyte leakage and O2− and H2O2 accumulation when subjected to salt stress. Moreover, the activity of reactive oxygen species (ROS)-scavenging enzymes was enhanced in S. miltiorrhiza via the overexpression of AtMYB12, and transgenic plants showed higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities compared with those of the wild type (WT) under salt stress, coupled with lower malondialdehyde (MDA) levels. In addition, the amount of salvianolic acid B was significantly elevated in all AtMYB12 transgenic hair roots and transgenic plants, and qRT-PCR analysis revealed that most genes in the phenolic acid biosynthetic pathway were up-regulated. In conclusion, these results demonstrated that AtMYB12 can significantly improve the resistance of plants to salt stress and promote the biosynthesis of phenolic acids by regulating genes involved in the biosynthetic pathway.
Heterogeneous Cellular Response of Primary and Metastatic Human Gastric Adenocarcinoma Cell Lines to Magnoflorine and Its Additive Interaction with Docetaxel
Authors: Grabarska Aneta , Luszczki Jarogniew J. , Gawel Kinga , Kukula-Koch Wirginia , Juszczak Małgorzata , Slawinska-Brych Adrianna , Adamczuk Grzegorz , Dmoszynska-Graniczka Magdalena , Kosheva Nataliia , Rzeski Wojciech , Stepulak Andrzej
Published: October 2023

Gastric cancer is the most common cancer and remains the leading cause of cancer death worldwide. In this study, the anticancer action of magnoflorine isolated via counter-current chromatography from the methanolic extract of Berberis vulgaris root against gastric cancer in models of primary ACC-201 and AGS and metastatic MKN-74 and NCI-N87 cell lines was analyzed. Cell viability and proliferation were tested through the use of MTT and BrdU tests, respectively. Cell cycle progression and apoptosis were evaluated using flow cytometry. The interaction of magnoflorine and docetaxel has been examined through isobolographic analysis. Moreover, potential toxicity was verified in zebrafish in an in vivo model. Gastric cancer cell lines revealed different responses to magnoflorine treatment with regard to viability/proliferation, apoptosis induction and cell cycle inhibition without any undesirable changes in the development of larval zebrafish at the tested concentrations. What is more, magnoflorine in combination with docetaxel produced an additive pharmacological interaction in all studied gastric cancer cell lines, which may suggest a complementary mechanism of action of both compounds. Taken together, these findings provide a foundation for the possibility of magnoflorine as a potential therapeutic approach for gastric cancer and merits further investigation, which may pave the way for clinical uses of magnoflorine.
The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target
Authors: Zhou Ziyi , Feng Zhaochen , Sun Xiaojia , Wang Yusheng , Dou Guorui
Published: October 2023

Galectin-3 is the most studied member of the Galectin family, with a large range of mediation in biological activities such as cell growth, proliferation, apoptosis, differentiation, cell adhesion, and tissue repair, as well as in pathological processes such as inflammation, tissue fibrosis, and angiogenesis. As is known to all, inflammation, aberrant cell apoptosis, and neovascularization are the main pathophysiological processes in retinal degeneration and many ocular diseases. Therefore, the review aims to conclude the role of Gal3 in the retinal degeneration of various diseases as well as the occurrence and development of the diseases and discuss its molecular mechanisms according to research in systemic diseases. At the same time, we summarized the predictive role of Gal3 as a biomarker and the clinical application of its inhibitors to discuss the possibility of Gal3 as a novel target for the treatment of ocular diseases.
Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors
Authors: Mushebenge Aganze Gloire-Aimé , Ugbaja Samuel Chima , Mbatha Nonkululeko Avril , B. Khan Rene , Kumalo Hezekiel M.
Published: October 2023

The COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, and transmembrane protease serine 2 (TMPRSS2). In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat Mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of the drug candidates to target receptors, providing insight into their potential efficacy. This study is aimed at assessing the useful contributions of the application of computational instruments in the discovery of receptors targeted in SARS-CoV-2. It further highlights some identified advantages and limitations of these studies, thereby revealing some complementary experimental validation to ensure the efficacy and safety of identified drug candidates.
Cordyceps militaris Solid Medium Extract Alleviates Lipoteichoic Acid-Induced MH-S Inflammation by Inhibiting TLR2/NF-κB/NLRP3 Pathways
Authors: Wang Xiaoya , Peng Zhiping , Wang Lei , Zhang Jingyan , Zhang Kang , Guo Zhiting , Xu Guowei , Li Jianxi
Published: October 2023

The aim of this study was to investigate the inhibitory effects of Cordyceps militaris solid medium extract (CME) and cordycepin (COR) on LTA-induced inflammation in MH-S cells and their mechanisms of action. In this study, the establishment of an LTA-induced MH-S inflammation model was determined, the CCK-8 method was used to determine the safe concentration range for a drug for COR and CME, the optimal concentration of COR and CME to exert anti-inflammatory effects was further selected, and the expression of inflammatory factors of TNF-α, IL-1β, IL-18, and IL-6 was detected using ELISA. The relative expression of TNF-α, IL-1β, IL-18, IL-6, IL-10, TLR2 and MyD88 mRNA was detected using RT-PCR, and the IL-1β, IL-18, TLR2, MyD88, NF-κB p-p65, NLRP3, pro-caspase-1, Caspase-1 and ASC protein expression in the cells were detected using Western blot; immunofluorescence assay detected the expression of Caspase-1 in MH-S cells. The results revealed that both CME and COR inhibited the levels of IL-1β, IL-18, IL-6, and TNF-α in the supernatants of LTA-induced MH-S cells and the mRNA expression levels of IL-1β, IL-18, IL-6, TNF-α, TLR2 and MyD88, down-regulated the LTA-induced IL-1β, IL-18, TLR2 in MH-S cells, MyD88, NF-κB p-p65/p65, NLRP3, ASC, pro-caspase-1, and caspase-1 protein expression levels, and inhibited LTA-induced caspase-1 activation in MH-S cells. In conclusion, CME can play a therapeutic role in LTA-induced inflammation in MH-S cells via TLR2/NF-κB/NLRP3, and may serve as a potential drug for bacterial pneumonia caused by Gram-positive bacteria.
Pioglitazone Protects Tubular Epithelial Cells during Kidney Fibrosis by Attenuating miRNA Dysregulation and Autophagy Dysfunction Induced by TGF-β
Authors: Manzéger Anna , Garmaa Gantsetseg , Mózes Miklós M. , Hansmann Georg , Kökény Gábor
Published: October 2023

Excessive renal TGF-β production and pro-fibrotic miRNAs are important drivers of kidney fibrosis that lack any efficient treatment. Dysfunctional autophagy might play an important role in the pathogenesis. We aimed to study the yet unknown effects of peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (Pio) on renal autophagy and miRNA dysregulation during fibrosis. Mouse primary tubular epithelial cells (PTEC) were isolated, pre-treated with 5 µM pioglitazone, and then stimulated with 10 ng/mL TGF-β1 for 24 h. Male 10-week-old C57Bl6 control (CTL) and TGF-β overexpressing mice were fed with regular chow (TGF) or Pio-containing chow (20 mg/kg/day) for 5 weeks (TGF + Pio). PTEC and kidneys were evaluated for mRNA and protein expression. In PTEC, pioglitazone attenuated (p < 0.05) the TGF-β-induced up-regulation of Col1a1 (1.4-fold), Tgfb1 (2.2-fold), Ctgf (1.5-fold), Egr2 (2.5-fold) mRNAs, miR-130a (1.6-fold), and miR-199a (1.5-fold), inhibited epithelial-to-mesenchymal transition, and rescued autophagy function. In TGF mice, pioglitazone greatly improved kidney fibrosis and related dysfunctional autophagy (increased LC3-II/I ratio and reduced SQSTM1 protein content (p < 0.05)). These were accompanied by 5-fold, 3-fold, 12-fold, and 2-fold suppression (p < 0.05) of renal Ccl2, Il6, C3, and Lgals3 mRNA expression, respectively. Our results implicate that pioglitazone counteracts multiple pro-fibrotic processes in the kidney, including autophagy dysfunction and miRNA dysregulation.
OmpC and OmpF Outer Membrane Proteins of Escherichia coli and Salmonella enterica Form Bona Fide Amyloids
Authors: Belousov Mikhail V. , Kosolapova Anastasiia O. , Fayoud Haidar , Sulatsky Maksim I. , Sulatskaya Anna I. , Romanenko Maria N. , Bobylev Alexander G. , Antonets Kirill S. , Nizhnikov Anton A.
Published: October 2023

Outer membrane proteins (Omps) of Gram-negative bacteria represent porins involved in a wide range of virulence- and pathogenesis-related cellular processes, including transport, adhesion, penetration, and the colonization of host tissues. Most outer membrane porins share a specific spatial structure called the β-barrel that provides their structural integrity within the membrane lipid bilayer. Recent data suggest that outer membrane proteins from several bacterial species are able to adopt the amyloid state alternative to their β-barrel structure. Amyloids are protein fibrils with a specific spatial structure called the cross-β that gives them an unusual resistance to different physicochemical influences. Various bacterial amyloids are known to be involved in host-pathogen and host-symbiont interactions and contribute to colonization of host tissues. Such an ability of outer membrane porins to adopt amyloid state might represent an important mechanism of bacterial virulence. In this work, we investigated the amyloid properties of the OmpC and OmpF porins from two species belonging to Enterobacteriaceae family, Escherichia coli, and Salmonella enterica. We demonstrated that OmpC and OmpF of E. coli and S. enterica form toxic fibrillar aggregates in vitro. These aggregates exhibit birefringence upon binding Congo Red dye and show characteristic reflections under X-ray diffraction. Thus, we confirmed amyloid properties for OmpC of E. coli and demonstrated bona fide amyloid properties for three novel proteins: OmpC of S. enterica and OmpF of E. coli and S. enterica in vitro. All four studied porins were shown to form amyloid fibrils at the surface of E. coli cells in the curli-dependent amyloid generator system. Moreover, we found that overexpression of recombinant OmpC and OmpF in the E. coli BL21 strain leads to the formation of detergent- and protease-resistant amyloid-like aggregates and enhances the birefringence of bacterial cultures stained with Congo Red. We also detected detergent- and protease-resistant aggregates comprising OmpC and OmpF in S. enterica culture. These data are important in the context of understanding the structural dualism of Omps and its relation to pathogenesis.
Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study
Authors: Gangwar Anamika , Deodhar Sneha S. , Saldanha Suzanne , Melander Olle , Abbasi Fahim , Pearce Ryan W. , Collier Timothy S. , McPhaul Michael J. , Furtado Jeremy D. , Sacks Frank M. , Merrill Nathaniel J. , McDermott Jason E. , Melchior John T. , Rohatgi Anand
Published: October 2023

High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature.
Improving the Biological Properties of Thrombin-Binding Aptamer by Incorporation of 8-Bromo-2′-Deoxyguanosine and 2′-Substituted RNA Analogues
Authors: Virgilio Antonella , Benigno Daniela , Aliberti Carla , Vellecco Valentina , Bucci Mariarosaria , Esposito Veronica , Galeone Aldo
Published: October 2023

Thrombin-binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers. By adopting its peculiar chair-like G4 structure, TBA can efficiently bind to thrombin, thus producing an anticoagulant effect. The major limit to its therapeutic application is represented by its poor thermal and biological resistance. Therefore, numerous research studies have been focused on the design of TBA analogues with chemical modifications to improve its pharmacokinetic and pharmacodynamic properties. To maintain the functional recognition to protein surface on which TBA anticoagulant activity depends, it is essential to preserve the canonical antiparallel topology of the TBA quadruplex core. In this paper, we have designed three TBA variants with modified G-tetrads to evaluate the effects of nucleobase and sugar moiety chemical modifications on biological properties of TBA, preserving its chair-like G-quadruplex structure. All derivatives contain 8-bromo-2′-deoxyguanosine (GBr) in syn positions, while in the anti-positions, locked nucleic acid guanosine (GLNA) in the analogue TBABL, 2’-O-methylguanosine (GOMe) in TBABM, and 2’-F-riboguanosine (GF) in TBABF is present. CD (Circular Dichroism), CD melting, 1H-NMR (Nuclear Magnetic Resonance), and non-denaturing PAGE (Polyacrylamide Gel Electrophoresis), nuclease stability, prothrombin time (PT) and fibrinogen-clotting assays have been performed to investigate the structural and biological properties of these TBA analogues. The most interesting results have been obtained with TBABF, which revealed extraordinary thermal stability (Tm approximately 40 °C higher than that of TBA), anticoagulant activity almost doubled compared to the original aptamer, and, above all, a never-observed resistance to nucleases, as 50% of its G4 species was still present in 50% FBS at 24 h. These data indicate TBABF as one of the best TBA analogue ever designed and investigated, to the best of our knowledge, overcoming the main limitations to therapeutic applications of this aptamer.
Changes in Lipoprotein(a) Levels in People after ST Elevation Myocardial Infarction—The STEMI-Lipids Study
Authors: Sourij Caren , Aziz Faisal , Krappinger Sarah , Praschk Andreas , Metzner Thomas , Kojzar Harald , Zirlik Andreas , Stojakovic Tatjana , Pätzold Dieter , von Lewinski Dirk , Zweiker Robert , Scharnagl Hubert , Sourij Harald
Published: October 2023

Lipoprotein(a) (Lp(a)) is considered an independent risk factor for cardiovascular diseases. The plasma concentration of Lp(a) is largely genetically determined but varies over a wide range within the population. This study investigated changes in Lp(a) levels after an acute myocardial infarction. Patients who underwent coronary angiography due to an ST elevation myocardial infarction were enrolled (n = 86), and Lp(a) levels were measured immediately after the intervention, one day, two days, and at a post-discharge follow-up visit at 3 to 6 months after the acute myocardial infarction. Median Lp(a) levels increased from a median of 7.9 mg/dL (3.8–37.1) at hospital admission to 8.4 mg/dL (3.9–35.4) on the following day, then to 9.3 mg/dL (3.7–39.1) on day two (p < 0.001), and to 11.2 mg/dL (4.4–59.6) at the post-discharge follow-up (p < 0.001). Lp(a) levels were the lowest during the acute myocardial infarction and started to increase significantly immediately thereafter, with the highest levels at the post-discharge follow-up. The moderate but significant increase in Lp(a) in people with acute myocardial infarction appears to be clinically relevant on an individual basis, especially when specific Lp(a) cut-off levels are supposed to determine the initiation of future treatment. Hence, a repeated measurement of Lp(a) after myocardial infarction should be performed.
Serum VEGF and CGRP Biomarkers: Relationships with Pain Intensity, Electric Pain, Pressure Pain Threshold, and Clinical Symptoms in Fibromyalgia—An Observational Study
Authors: Tapia-Haro Rosa Mª , Molina Francisco , Rus Alma , Casas-Barragán Antonio , Correa-Rodríguez María , Aguilar-Ferrándiz Mª Encarnación
Published: October 2023

Fibromyalgia (FM) is a multifactorial syndrome, mainly characterized by chronic widespread pain, whose physiopathology is yet to be determined. Reliable biomarkers for FM and how they are associated with the symptomatology have not yet been identified. We aimed to examine the relationships among serum vascular endothelial growth factor (VEGF) and calcitonin gene-related peptide (CGRP) levels with clinical manifestations and pain-related variables in women with FM. We conducted an observational case study with forty-seven women diagnosed with FM. Serum VEGF and CGRP levels were spectrophotometrically analyzed. We used questionnaires to measure the impact of FM and the degree of central sensitization, fatigue, and anxiety. We also assessed pain intensity, electric pain threshold and magnitude, and pressure pain threshold (PPT) in tender points. The linear regression analysis adjusting for age, menopause status, and body mass index showed that serum VEGF levels were significantly associated with the PPTs of non-dominant trapezius (β = 153.418; p = 0.033), non-dominant second metacarpal (β = 174.676; p = 0.008) and dominant tibialis anterior (β = 115.080; p = 0.049) in women with FM. We found no association between serum CGRP levels and the variables measured (p ≥ 0.152). Our results suggest that VEGF may be related to pain processing in patients with FM.
METTL3-Dependent N6-Methyladenosine Modification Programs Human Neural Progenitor Cell Proliferation
Authors: Zhao Yuan , Li Jianguo , Lian Yilin , Zhou Qian , Wu Yukang , Kang Jiuhong
Published: October 2023

METTL3, a methyltransferase responsible for N6−methyladenosine (m6A) modification, plays key regulatory roles in mammal central neural system (CNS) development. However, the specific epigenetic mechanisms governing human CNS development remain poorly elucidated. Here, we generated small−molecule−assisted shut−off (SMASh)−tagged hESC lines to reduce METTL3 protein levels, and found that METTL3 is not required for human neural progenitor cell (hNPC) formation and neuron differentiation. However, METTL3 deficiency inhibited hNPC proliferation by reducing SLIT2 expression. Mechanistic studies revealed that METTL3 degradation in hNPCs significantly decreased the enrichment of m6A in SLIT2 mRNA, consequently reducing its expression. Our findings reveal a novel functional target (SLIT2) for METTL3 in hNPCs and contribute to a better understanding of m6A−dependent mechanisms in hNPC proliferation.
The Effects of Stress on Hippocampal Neurogenesis and Behavior in the Absence of Lipocalin-2
Authors: Ferreira Ana Catarina , Marques Fernanda
Published: October 2023

Lipocalin-2 (LCN2) is an acute phase protein able to bind iron when complexed with bacterial siderophores. The recent identification of a mammalian siderophore also suggested a physiological role for LCN2 in the regulation of iron levels and redox state. In the central nervous system, the deletion of LCN2 induces deficits in neural stem cells proliferation and commitment, with an impact on the hippocampal-dependent contextual fear discriminative task. Additionally, stress is a well-known regulator of cell genesis and is known to decrease adult hippocampal cell proliferation and neurogenesis. Although voluntary running, another well-known regulator of neurogenesis, is sufficient to rescue the defective hippocampal neurogenesis and behavior in LCN2-null mice by promoting stem cells’ cell cycle progression and maturation, the relevance of LCN2-regulated hippocampal neurogenesis in response to stress has never been explored. Here, we show a lack of response by LCN2-null mice to the effects of chronic stress exposure at the cellular and behavioral levels. Together, these findings implicate LCN2 as a relevant mediator of neuronal plasticity and brain function in the adult mammalian brain.
Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus
Authors: Dias de Oliveira Felipe Bruno , Antonioli Eliane , Dias Olívia Furiama Metropolo , de Souza Jean Gabriel , Agarwal Sudha , Chudzinski-Tavassi Ana Marisa , Ferretti Mario
Published: October 2023

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM–OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.
Influence of High Concentrations of Copper Sulfate on In Vitro Adventitious Organogenesis of Cucumis sativus L.
Authors: Miguel Jorge Fonseca
Published: October 2023

Copper (Cu) is an essential plant micronutrient. This report is the first to assess the effects of high copper sulfate (CuSO4) levels on in vitro callus and shoot formation of cucumber. Four-day-old cotyledon explants from the inbred line Wisconsin 2843 and the commercial cultivars Marketer and Negrito were used. Murashige and Skoog (MS)-derived callus and shoot induction medium containing 0.5 mg L−1 indole-3-acetic acid (IAA) and 2.5 mg L−1 6-benzylaminopurine (BAP) was supplemented with CuSO4 (0.2–5 mg L−1). The response on callus-derived shoots showed that the optimal concentration of CuSO4 was 8- to 200-fold greater than in standard MS medium. Shoot frequency (SF) and shoot number (SN) were assessed, and Marketer > Negrito > Wisconsin 2843, where 1, 0.2 and 5 mg L−1 CuSO4 produced the highest results, respectively. SF and SN increased 6- and 10-fold in Wisconsin 2843 and twice in the other cultivars. All explants formed calluses, and in two of the three cultivars, callus extension was significantly affected by CuSO4 application. SN showed a strong relationship with CuSO4 levels and no association with callus extension. The results show that specific CuSO4 concentrations higher than in standard MS medium increase adventitious cucumber shoot organogenesis.
High-Avidity Anti-Filovirus IgG Elicited Using Protein Subunit Vaccines Does Not Correlate with Protection
Authors: Williams Caitlin A. , Wong Teri Ann S. , Lieberman Michael M. , Yalley-Ogunro Jake , Cabus Mehtap , Nezami Sara , Paz Fabian , Andersen Hanne , Geisbert Thomas W. , Lehrer Axel T.
Published: October 2023

Zaire ebolavirus (EBOV) poses a significant threat to public health due to its high case fatality rate and epidemic potential. This is further complicated by the lack of precise immune correlates of protection and difficulties in conducting in vivo animal studies due to species specificity of Ebola virus disease (EVD) and classification as a biosafety level 4 pathogen. Related ebolaviruses have also contributed to the public health threat; Uganda recently experienced an outbreak of Sudan ebolavirus, which also had a high case fatality rate. Vaccination targeting EBOV has demonstrated significant efficacy; however, the protective cellular and humoral responses at play are still poorly understood. Vaccination for vulnerable populations such as pregnant women, young children, and immunocompromised individuals is still limited. Understanding vaccine correlates of protection (vCOP) is key to developing alternative vaccination strategies for these groups. Components of immunity such as neutralizing antibody and cell-mediated immunity are likely responsible for protective responses; however, existing research fails to fully define their roles in protection. Here we investigated vaccine-elicited antibody avidity as a potential correlate of protection and to further characterize the contribution of antibody avidity in protective and nonprotective vaccine responses.
Contact Efficacy of Two Amorphous Silica Powders against the Red Flour Beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae)
Authors: Manivannan Selladurai , Subramanyam Bhadriraju
Published: October 2023

The contact efficacy of two amorphous silica powders 1 and 2 procured from Imery’s chemicals, Lompoc, CA, USA, were evaluated against the red flour beetle, Tribolium castaneum (Herbst). The efficacy of the silica two powders was evaluated by exposing 10 adults of T. castaneum to twelve different concentrations of silica powder 1 and 2 for 12, 24, 36, and 48 h. Mortality assessments were made after 14 d, and data on adult progeny production were recorded at 42 d. Complete mortality of T. castaneum was observed when adults were exposed for 36 h to concentrations of 1.5 to 5 g/m2 of silica powder 1. Conversely, in tests with silica powder 2, complete mortality was only achieved when adults were exposed for 48 h to concentrations ranging from 0.75 to 5 g/m2. Silica powder 1 exhibited greater efficacy in inhibiting adult progeny production in T. castaneum, particularly at a concentration of 2.0 g/m2 after 24 h exposure. Overall, silica powder 1 displayed superior performance in terms of adult mortality and the suppression of T. castaneum adult progeny production. This advantage can be attributed to the smaller particle size of silica powder 1 when compared to silica powder 2.
Attosecond Pulses from Ionization Injection Wakefield Accelerators
Authors: Tomassini Paolo , Horny Vojtech , Doria Domenico
Published: October 2023

High-quality ionization injection methods for wakefield acceleration driven by lasers or charged beams (LWFA/PWFA) can be optimized so as to generate high-brightness electron beams with tuneable duration in the attosecond range. We present a model of the minimum bunch duration obtainable with low-emittance ionization injection schemes by spotting the roles of the ionization pulse duration, of the wakefield longitudinal shape and of the delay of the ionization pulse position with respect to the node of the accelerating field. The model is tested for the resonant multi-pulse ionization injection (ReMPI) scheme, showing that bunches having a length of about 300 as can be obtained with an ionization pulse having a duration of 30 fs FWHM.
K-mer Frequency Encoding Model for Cable Defect Identification: A Combination of Non-Destructive Testing Approach with Artificial Intelligence
Authors: Patel Brijesh , Huang Zih Fong , Yeh Chih-Ho , Shih Yen-Ru , Lin Po Ting
Published: October 2023

This paper describes a non-destructive detection method for identifying cable defects using K-mer frequency encoding. The detection methodology combines magnetic leakage detection equipment with artificial intelligence for precise identification. The cable defect identification process includes cable signal acquisition, K-mer frequency encoding, and artificial intelligence-based identification. A magnetic leakage detection device detects signals via sensors and records their corresponding positions to obtain cable signals. The K-mer frequency encoding method consists of several steps, including cable signal normalization, the establishment of K-mer frequency encoding, repeated sampling of cable signals, and conversion for comparison to derive the K-mer frequency. The K-mer frequency coding method has advantages in data processing and repeated sampling. In the identification step of the artificial intelligence identification model, an autoencoder model is used as the algorithm, and the K-mer frequency coding method is used to introduce artificial parameters. Proper adjustments of these parameters are required for optimal cable defect identification performance in various applications and usage scenarios. Experiment results show that the proposed K-mer frequency encoding method is effective, with a cable identification accuracy rate of 91% achieved through repeated sampling.
Social Connectedness in a Locked-Down World: A Phenomenological Study of Older Adults during the COVID-19 Pandemic
Authors: Beardmore Amy , Beynon Penny , Crabbe Christine , Fullforth Jan , Groome Jeremy , Jones Matthew
Published: October 2023

Background: Whilst qualitative research has previously been conducted on older people’s personal resilience and wellbeing during COVID-19, there are fewer empirical studies on the impact it had on social connectedness for this age group. In this paper we seek to examine older people’s social connectedness to others during the pandemic, their personal experiences of seeking out those connections, and whether there are any identifiable pre-existing factors that enabled them to minimise the impact of enforced isolation. Methods: Using a phenomenological methodology, we conducted in-depth interviews with 13 older people between March and May 2021. These interviews explored the participant’s lived experiences of staying socially connected to others during the enforced lockdowns and various restrictions. Results: Our findings reveal strong themes of personal resilience, sense of coherence and other protective factors, but also highlight the benefits of establishing connections to friends, family, organised groups and community prior to the pandemic. Conclusion: Older people’s ability to stay socially connected is influenced by personal resilience and a positive mindset; pre-existing social ties to others and maintaining a personal sense of coherence and a sense of belonging to people or places. Our findings shed light on the importance of informal social interactions, what it means to feel lonely in older age and indicate that for some the pandemic restrictions may even have offered a welcome space in which to process significant life events.
Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation
Authors: Carmona Rita , López-Sánchez Carmen , Garcia-Martinez Virginio , Garcia-López Virginio , Muñoz-Chápuli Ramón , Lozano-Velasco Estefanía , Franco Diego
Published: October 2023

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of an epithelial–mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.
Mild Cardiotoxicity and Continued Trastuzumab Treatment in the Context of HER2-Positive Breast Cancer
Authors: de la Brassinne Bonardeaux Orianne , Born Benjamin , Moonen Marie , Lancellotti Patrizio
Published: October 2023

Breast cancer is the leading cause of cancer death in women worldwide. Trastuzumab, the main HER2-targeted treatment, faces limitations due to potential cardiotoxicity. The management of patients with mild cardiotoxicity on trastuzumab remains uncertain, resulting in treatment discontinuation and negative oncological outcomes. This retrospective study analyzed 23 patients who experienced decreased left ventricular function during trastuzumab treatment. During the 18-month follow-up period, two patients (9%) had severe declines in function, leading to treatment cessation, and one patient (4%) developed heart failure symptoms. However, 21 patients showed mild, reversible myocardial dysfunction without significant differences in final ventricular function compared to a control group (58.4% vs. 61.7%, respectively; p = 0.059). The declines in function were most pronounced at nine months but improved at twelve and eighteen months. Various echocardiographic parameters changed significantly over time. As predictors of severe cardiotoxicity, we identified the following: LVEF before initial chemotherapy (p = 0.022), as well as baseline LVEF before treatment with trastuzumab (p = 0.007); initial left ventricular end systolic volume (p = 0.027); and the initial global longitudinal strain (p = 0.021) and initial velocity time integral in the left ventricular outflow track (p = 0.027). In conclusion, the continuation of trastuzumab should be considered for most patients with mild cardiotoxicity, with close cardiac monitoring and cardioprotective measures. However, identifying the patients at risk of developing severe cardiotoxicity is necessary. According to our data, the initial LVEF and GLS levels appear to be reliable predictors.