bluuebunny/crossref_metadata_2025 huggingface dataset:
Intron Editing Reveals SNORD-Dependent Maturation of the Small Nucleolar RNA Host Gene GAS5 in Human Cells
Authors: Matveeva Anastasiya , Vinogradov Dmitry , Zhuravlev Evgenii , Semenov Dmitriy , Vlassov Valentin , Stepanov Grigory
Published: December 2023

The GAS5 gene encodes a long non-coding RNA (lncRNA) and intron-located small nucleolar RNAs (snoRNAs). Its structure, splice variants, and diverse functions in mammalian cells have been thoroughly investigated. However, there are still no data on a successful knockout of GAS5 in human cells, with most of the loss-of-function experiments utilizing standard techniques to produce knockdowns. By using CRISPR/Cas9 to introduce double-strand breaks in the terminal intronic box C/D snoRNA genes (SNORDs), we created monoclonal cell lines carrying continuous deletions in one of the GAS5 alleles. The levels of GAS5-encoded box C/D snoRNAs and lncRNA GAS5 were assessed, and the formation of the novel splice variants was analyzed. To comprehensively evaluate the influence of specific SNORD mutations, human cell lines with individual mutations in SNORD74 and SNORD81 were obtained. Specific mutations in SNORD74 led to the downregulation of all GAS5-encoded SNORDs and GAS5 lncRNA. Further analysis revealed that SNORD74 contains a specific regulatory element modulating the maturation of the GAS5 precursor transcript. The results demonstrate that the maturation of GAS5 occurs through the m6A-associated pathway in a SNORD-dependent manner, which is a quite intriguing epitranscriptomic mechanism.
Characteristics of Interpolyelectrolyte Complexes Based on Different Types of Pectin with Eudragit® EPO as Novel Carriers for Colon-Specific Drug Delivery
Authors: Nasibullin Shamil F. , Dunaeva Julia V. , Akramova Lilija A. , Timergalieva Venera R. , Moustafine Rouslan I.
Published: December 2023

Given that pectin is a well-known substance used for drug delivery, we aimed to obtain and further examine the efficacy of interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO for using these carriers in oral drug delivery. To characterize the physicochemical properties of these compounds, turbidity, gravimetry, viscosity, elementary analysis, FTIR spectroscopy, and DSC analysis were utilized. Diffusion transport characteristics were evaluated to assess the swelling ability of the matrices and the release of diclofenac sodium. To examine the release parameters, mathematical modeling was performed by using the Korsmayer–Peppas and Logistic equations as well. During the turbidity study, stoichiometry compositions were selected for the developed IPECs EPO/PecA and EPO/PecC at pH values = 4.0, 5.0, 6.0, and 7.0. The FTIR spectra of the complexes were characterized by an increase in the intensity of the bands at 1610 cm−1 and 1400 cm−1. According to the DSC analysis, IPEC has a certain Tg = 57.3 °C. The highest release rates were obtained for IPEC EPO/PecC_1 and EPO/PecC_4. The mechanism of drug transport from the matrices IPEC EPO/PecC, IPEC EPO/PecA_3, and EPO/PecA_4 can be characterized as Super Case II. Anomalous release (non-Fickian release) is typical for IPEC EPO/PecA_1 and EPO/PecA_2. Thus, the resulting systems can be further used for the effective delivery of the drugs to the colon.
Identification of the Axis β-Catenin–BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment
Authors: Mihoub Imane , Rharass Tareck , Ouriemmi Souhaïl , Oudar Antonin , Aubard Laure , Gratio Valérie , Lazarian Gregory , Ferreira Jordan , Dondi Elisabetta , Cymbalista Florence , Levy Vincent , Baran-Marszak Fanny , Varin-Blank Nadine , Ledoux Dominique , Le Roy Christine , Gardano Laura
Published: December 2023

In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell–cell interactions and regulates cell survival through its transcriptional activity. We used chronic lymphocytic leukemia (CLL) cells as a cellular model to study the role of β-catenin in regulating the adhesion of tumor cells to their microenvironment, which is necessary for tumor cell survival and accumulation. When co-cultured with a stromal cell line (HS-5), a fraction of the CLL cells adhere to stromal cells in a dynamic fashion regulated by the different levels of β-catenin expression. In non-adherent cells, β-catenin is stabilized in the cytosol and translocates into the nucleus, increasing the expression of cyclin D1. In adherent cells, the level of cytosolic β-catenin is low but membrane β-catenin helps to stabilize the adhesion of CLL to stromal cells. Indeed, the overexpression of β-catenin enhances the interaction of CLL with HS-5 cells, suggesting that this protein behaves as a regulator of cell adhesion to the stromal component and of the transcriptional regulation of cell survival. Inhibitors that block the stabilization of β-catenin alter this equilibrium and effectively disrupt the support that CLL cells receive from the cross-talk with the stroma.
The Genetic Dissection of Nitrogen Use-Related Traits in Flax (Linum usitatissimum L.) at the Seedling Stage through the Integration of Multi-Locus GWAS, RNA-seq and Genomic Selection
Authors: Soto-Cerda Braulio J. , Larama Giovanni , Cloutier Sylvie , Fofana Bourlaye , Inostroza-Blancheteau Claudio , Aravena Gabriela
Published: December 2023

Nitrogen (N), the most important macro-nutrient for plant growth and development, is a key factor that determines crop yield. Yet its excessive applications pollute the environment and are expensive. Hence, studying nitrogen use efficiency (NUE) in crops is fundamental for sustainable agriculture. Here, an association panel consisting of 123 flax accessions was evaluated for 21 NUE-related traits at the seedling stage under optimum N (N+) and N deficiency (N−) treatments to dissect the genetic architecture of NUE-related traits using a multi-omics approach integrating genome-wide association studies (GWAS), transcriptome analysis and genomic selection (GS). Root traits exhibited significant and positive correlations with NUE under N− conditions (r = 0.33 to 0.43, p < 0.05). A total of 359 QTLs were identified, accounting for 0.11% to 23.1% of the phenotypic variation in NUE-related traits. Transcriptomic analysis identified 1034 differentially expressed genes (DEGs) under contrasting N conditions. DEGs involved in N metabolism, root development, amino acid transport and catabolism and others, were found near the QTLs. GS models to predict NUE stress tolerance index (NUE_STI) trait were tested using a random genome-wide SNP dataset and a GWAS-derived QTLs dataset. The latter produced superior prediction accuracy (r = 0.62 to 0.79) compared to the genome-wide SNP marker dataset (r = 0.11) for NUE_STI. Our results provide insights into the QTL architecture of NUE-related traits, identify candidate genes for further studies, and propose genomic breeding tools to achieve superior NUE in flax under low N input.
Correlation of MR-Based Metabolomics and Molecular Profiling in the Tumor Microenvironment of Temozolomide-Treated Orthotopic GL261 Glioblastoma in Mice
Authors: Zhao Kai , Calero-Pérez Pilar , Bopp Miriam H. A. , Möschl Vincent , Pagenstecher Axel , Mulero-Acevedo Marta , Vázquez Mario , Barcia Carlos , Arús Carles , Nimsky Christopher , Rusch Tillmann , Bartsch Jörg W. , Candiota Ana Paula
Published: December 2023

The tumor microenvironment in glioblastoma (GB) is considered to be “cold”, i.e., the fraction of cytotoxic T cells, for instance, is low. Instead, macrophages are the major immune cell population in GB, which stem either from tissue response (resident microglia) or recruitment of macrophages from the periphery, thereby undergoing tumor-dependent “imprinting” mechanisms by which macrophages can adapt a tumor-supportive phenotype. In this regard, it is important to describe the nature of macrophages associated with GB, in particular under therapy conditions using the gold standard chemotherapy drug temozolomide (TMZ). Here, we explored the suitability of combining information from in vivo magnetic resonance spectroscopic (MRS) approaches (metabolomics) with in vitro molecular analyses to assess therapy response and characterize macrophage populations in mouse GB using an isogenic GL261 model. For macrophage profiling, expression levels of matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs) were determined, since their gene products affect macrophage–tumor cell communication by extensive cleavage of immunomodulatory membrane proteins, such as PD-L1. In tumor mice with an overall therapy response, expression of genes encoding the proteases ADAM8, ADAM10, and ADAM17 was increased and might contribute to the immunosuppressive phenotype of GB and immune cells. In tumors responding to therapy, expression levels of ADAM8 were upregulated by TMZ, and higher levels of PD-L1 were correlated significantly. Using a CRISPR/Cas9 knockout of ADAM8 in GL261 cells, we demonstrated that soluble PD-L1 (sPD-L1) is only generated in the presence of ADAM8. Moreover, primary macrophages from WT and ADAM8-deficient mice showed ADAM8-dependent release of sPD-L1, independent of the macrophage polarization state. Since ADAM8 expression is induced in responding tumors and PD-L1 shedding is likely to decrease the anti-tumor activities of T-cells, we conclude that immunotherapy resistance is caused, at least in part, by the increased presence of proteases, such as ADAM8.
An Insight into Functional Metagenomics: A High-Throughput Approach to Decipher Food–Microbiota–Host Interactions in the Human Gut
Authors: Mathieu Elliot , Léjard Véronique , Ezzine Chaima , Govindin Pauline , Morat Aurélien , Giat Margot , Lapaque Nicolas , Doré Joël , Blottière Hervé M.
Published: December 2023

Our understanding of the symbiotic relationship between the microbiota and its host has constantly evolved since our understanding that the “self” was not only defined by our genetic patrimony but also by the genomes of bugs living in us. The first culture-based methods highlighted the important functions of the microbiota. However, these methods had strong limitations and did not allow for a full understanding of the complex relationships that occur at the interface between the microbiota and the host. The recent development of metagenomic approaches has been a groundbreaking step towards this understanding. Its use has provided new insights and perspectives. In the present chapter, we will describe the advances of functional metagenomics to decipher food–microbiota and host–microbiota interactions. This powerful high-throughput approach allows for the assessment of the microbiota as a whole (including non-cultured bacteria) and enabled the discovery of new signaling pathways and functions involved in the crosstalk between food, the gut microbiota and its host. We will present the pipeline and highlight the most important studies that helped to develop the field. To conclude, we will emphasize the most recent developments and hot topics in functional metagenomics.
Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor
Authors: Zhuang Weiliang , Zhang Wei , Xie Liping , Wang Lei , Li Yuan , Wang Ziyu , Zhang Ao , Qiu Haitao , Feng Jun , Zhang Baohong , Hu Youjia
Published: December 2023

Antibody–drug conjugates (ADCs) have greatly improved the outcomes of advanced breast tumors. However, the treatment of breast tumors with existing ADCs is still hindered by many issues, such as tumor antigen heterogeneity and drug resistance. Therefore, ADCs against new targets would provide options for the treatment of these challenges. Sortilin-1 (SORT1) may be a promising target for ADC as it is upregulated in breast cancer. To evaluate the possibility of SORT1 as an ADC target, a humanized antibody_8D302 with high affinity against SORT1 was generated. Additionally, 8D302 was conjugated with MMAE and DXd to generate two ADCs_8D302-MMAE and 8D302-DXd, respectively. Both 8D302-MMAE and 8D302-DXd showed effective cytotoxicity against SORT1 positive breast tumor cell lines and induced bystander killing. Consequently, 8D302-MMAE showed relatively better anti-tumor activity than 8D302-DXd both in vitro and in vivo, but 8D302-DXd had superior safety profile and pharmacokinetics profile over 8D302-MMAE. Furthermore, SORT1 induced faster internalization and lysosomal trafficking of antibodies and had a higher turnover compared with HER2. Also, 8D302-DXd exhibited superior cell cytotoxicity and tumor suppression over trastuzumab-DXd, a HER2-targeted ADC. We hypothesize that the high turnover of SORT1 enables SORT1-targeted ADC to be a powerful agent for the treatment of SORT1-positive breast tumor.
Disruptive Effects of Two Curcuminoids (Demethoxycurcumin and Bisdemethoxycurcumin) on the Larval Development of Drosophila melanogaster
Authors: Jeon Jun-Hyoung , Jeong Seon-Ah , Park Doo-Sang , Park Hong-Hyun , Shin Sang-Woon , Oh Hyun-Woo
Published: December 2023

Juvenile hormones (JHs) play a central role in insect development, reproduction, and various physiological functions. Curcuminoids generally exhibit a wide range of biological activities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal, and they exhibit insect growth inhibitory effects. However, research on insecticidal properties of curcuminoids has been limited. Moreover, to the best of our knowledge, studies on JHs of insects and curcuminoids are lacking. Therefore, this study aimed to identify the substances that act as JH disruptors (JHDs) from edible plants. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), two curcuminoids from the turmeric plant Curcuma longa L. inhibited the formation of a methoprene-tolerant (Met)–Taiman (Tai) heterodimer complex in Drosophila melanogaster, as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) DMC or BDMC significantly reduced the number of D. melanogaster larvae in a concentration-dependent manner; larval development was disrupted, preventing the progression of larvae to pupal stages, resulting in an absence of adults. Building on the results obtained in this study on curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.
The Optimal Choice of Trap Type for the Recently Spreading Jewel Beetle Pests Lamprodila festiva and Agrilus sinuatus (Coleoptera, Buprestidae)
Authors: Matula Eszter , Bozsik Gábor , Muskovits József , Ruszák Csenge , Jávorszky Laura , Bonte Jochem , Paulin Márton , Vuts József , Fail József , Tóth Ágoston , Egri Ádám , Tóth Miklós , Imrei Zoltán
Published: December 2023

BACKGROUND: Two jewel beetle species native to Europe, the cypress jewel beetle, Lamprodila (Palmar, Ovalisia) festiva L. (Buprestidae, Coleoptera), and the sinuate pear tree borer, Agrilus sinuatus Olivier (Buprestidae, Coleoptera), are key pests of ornamental thuja and junipers and of orchard and ornamental rosaceous trees, respectively. Although chemical control measures are available, due to the beetles’ small size, agility, and cryptic lifestyle at the larval stage, efficient tools for their detection and monitoring are missing. Consequently, by the time emerging jewel beetle adults are noticed, the trees are typically significantly damaged. METHODS: Thus, the aim of this study was to initiate the development of monitoring traps. Transparent, light green, and purple sticky sheets and multifunnel traps were compared in field experiments in Hungary. RESULTS: Light green and transparent sticky traps caught more L. festiva and A. sinuatus jewel beetles than non-sticky multifunnel traps, regardless of the larger size of the colored surface of the funnel traps. CONCLUSIONS: Although light green sticky sheets turned out to be optimal for both species, using transparent sheets can reduce catches of non-target insects. The key to the effectiveness of sticky traps, despite their reduced suitability for quantitative comparisons, may lie in the behavioral responses of the beetles to the optical features of the traps.
Innovative Fabrication Design for In Situ Martensite Decomposition and Enhanced Mechanical Properties in Laser Powder Bed Fused Ti6Al4V Alloy
Authors: Farhang Behzad , Tanrikulu Ahmet Alptug , Ganesh-Ram Aditya , Durlov Sadman Hafiz , Shayesteh Moghaddam Narges
Published: December 2023

Ti6Al4V alloy (Ti64) is a popular material used in the aerospace, medical, and automotive industries due to its excellent mechanical properties. Laser Powder Bed Fusion (LPBF) is a promising manufacturing technique that can produce complex and net-shaped components with comparable mechanical properties to those produced using conventional manufacturing techniques. However, during LPBF, the rapid cooling of the material can limit its ductility, making it difficult to achieve high levels of ductility while maintaining the required tensile strength for critical applications. To address this challenge, this study presents a novel approach to controlling the microstructure of Ti64 during LPBF by using a border design surrounding the main parts. It is hypothesized that the design induces in situ martensitic decomposition at different levels during the fabrication process, which can enhance the ductility of the material without compromising its tensile strength. To achieve this aim, a series of Ti64 samples were fabricated using LPBF with varying border designs, including those without borders and with gaps from 0.5 to 4 mm. The microstructure, composition, and mechanical properties of the Reference sample were compared with those of the samples fabricated with the surrounding border design. It was found that the latter had a more homogenized microstructure, a higher density, and improvements in both ductility and tensile strength. Moreover, it was discovered that the level of property improvement and martensitic transformation can be controlled by adjusting the gap space between the border and the main part, providing flexibility in the fabrication process. Overall, this study presents a promising approach for enhancing the mechanical properties of Ti64 produced via LPBF, making it more suitable for critical applications in various industries.
Uncovering the State of Local News Databases in the UK: Limitations and Impacts on Research
Authors: Bisiani Simona , Heravi Bahareh
Published: December 2023

Local journalism is fundamental for a thriving democracy, yet the UK faces a decline in the number of print and digital local news outlets. Large-scale mappings of the surviving outlets offer invaluable insights to policymakers designing interventions to strengthen the sector. Due to the lack of a comprehensive national directory of UK print and digital local news outlets, researchers have resorted to datasets such as circulation auditors’ databases, which have been noted to be incomplete and outdated. A lack of understanding of the magnitude of these data limitations hinders researchers from selecting optimal datasets. This study evaluates four commonly used local news databases, uncovering significant variations in their currentness and comprehensiveness. Thereafter, statistical analyses demonstrate the significant effect of each dataset’s shortcomings on findings in local news research. To address this issue, triangulation and manual verification are employed to create a more comprehensive and robust dataset. This procedure generates a new national dataset of print and digital local news outlets that can be used in future research, alongside a framework for leveraging public data to build an independent research dataset. This work paves the way for more rigorous research in data-driven local news provision studies. Concluding remarks stress the importance of setting definitions and establishing clear data pipelines in an increasingly diversified and dynamic sector.
Paths of Constructionalization in Peninsular Spanish: The Development of “Pues Eso”. A 20th Century Case
Authors: Salameh Jiménez Shima
Published: December 2023

This paper explores the evolution of the conversational formula pues eso in Peninsular Spanish through the framework of constructionalization, so as to describe how form–meaning pairings have been consolidated. Additionally, the Val.Es.Co. model for discourse segmentation is introduced as part of the form pole in the construction. The findings suggest that PE has become a consolidated parenthetical, procedural device during the 20th century, but that previous centuries are also key in understanding how the new functions were developed from pues.
Evaluating the Potential of Multi-Walled Carbon Nanotube-Modified Clay as a Landfill Liner Material
Authors: Liu Xibin , Chen Zhengfa , Qi Lin
Published: December 2023

In this paper, the feasibility of multi-walled carbon nanotube (MWCNT)-modified clay as a landfill liner material is investigated. Experiments were conducted on the modified clay with 0.5%, 1%, and 2% MWCNTs. The effects of the MWCNTs on the compaction characteristics, permeability coefficient, stress–strain curve, peak deviation stress, shear strength parameters (internal friction angle and cohesion), microstructures, and adsorption performance of the clay were analyzed. The results showed that the optimum moisture content (OMC) increased from 16.15% to 18.89%, and the maximum dry density (MDD) decreased from 1.79 g/cm3 to 1.72 g/cm3 with the increase in MWCNTs. The permeability coefficients firstly fell and then gradually rose as the MWCNTs increased; the minimum permeability coefficient was 8.62 × 10−9 cm/s. The MWCNTs can also effectively increase the peak deviation stress of the clay, and at the maximum level, the peak deviation stress was increased by 286%. SEM images were processed using the Pore and Crack Analysis System (PCAS), and the results showed that the appropriate amount of MWCNTs could fill the pores and strengthen the clay structure. The effect of the MWCNT-modified clay on the adsorption performance of common heavy metal ions Cd2+, Mn2+ and Cu2+ in landfill leachate was analyzed by batch adsorption tests. The maximum adsorption capacities (Qmax) of Cu2+, Cd2+ and Mn2+ in the 2% MWCNT-modified clay were, respectively, 41.67 mg/g, 18.69 mg/g, and 4.97 mg/g. Compared with the clay samples without MWCNTs, the adsorption properties of Cu2+, Cd2+, and Mn2+ were increased by 228%, 124%, and 202%, respectively. Overall, the results suggest that MWCNT-modified clays have the potential to be suitable barrier materials for the construction of landfills.
Limit Distributions of Products of Independent and Identically Distributed Random 2 × 2 Stochastic Matrices: A Treatment with the Reciprocal of the Golden Ratio
Authors: Chakraborty Santanu
Published: December 2023

Consider a sequence (Xn)n≥1 of i.i.d. 2×2 stochastic matrices with each Xn distributed as μ. This μ is described as follows. Let (Cn,Dn)T denote the first column of Xn and for a given real r with 0<r<1, let r−1Cn and r−1Dn each be Bernoulli distributions with parameters p1 and p2, respectively, and 0<p1,p2<1. Clearly, the weak limit of the sequence μn, namely λ, is known to exist, whose support is contained in the set of all 2×2 rank one stochastic matrices. In a previous paper, we considered 0<r≤12 and obtained λ explicitly. We showed that λ is supported countably on many points, each with positive λ-mass. Of course, the case 012 is very challenging. Considering the extreme nontriviality of this case, we stick to a very special such r, namely, r=5−12 (the reciprocal of the golden ratio), briefly mention the challenges in this nontrivial case, and completely identify λ for a very special situation.
Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis
Authors: Medoro Alessandro , Davinelli Sergio , Milella Luigi , Willcox Bradley , Allsopp Richard , Scapagnini Giovanni , Willcox Donald
Published: December 2023

Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood–brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging.
Association of Visiting the Physiotherapist with Mortality in the Spanish General Population: A Population-Based Cohort Study
Authors: Nouni-García Rauf , Carbonell-Soliva Álvaro , Orozco-Beltrán Domingo , López-Pineda Adriana , Tomás-Rodríguez María Isabel , Gil-Guillén Vicente F. , Quesada José A. , Carratalá-Munuera Concepción
Published: December 2023

Background and Objectives: The purpose of this retrospective population-based cohort study was to analyse the association between attendance of physiotherapy with mortality in the Spanish general population and describe the profile of people who do not visit a physiotherapist in Spain. Material and Methods: The data sources were the 2011/2012 National Health Survey (ENSE11) and the national database of death in Spain, and the participants were all adult respondents in the ENSE11. Results: Of 20,397 people, 1101 (5.4%) visited the physiotherapist the previous year, and the cumulative incidence of total mortality was 5.4% (n = 1107) at a mean follow-up of 6.2 years. Visiting the physiotherapist was associated with lower all-cause mortality in the population residing in Spain, quantified at 30.1% [RR = 0.699; 95% CI (0.528–0.927); p = 0.013]. The factors associated with not visiting a physiotherapist were the following: rating one’s health as good (9.8%; n = 1017; p < 0.001), not having any hospital admission in the previous year (9.6%; n = 1788; p < 0.001), not having visited the general practitioner in the previous month (9.6%; n = 1408; p < 0.001), and not having attended a day hospital in the previous year (9.7%; n = 1836; p < 0.001). Conclusions: Visiting a physiotherapist was associated with a lower mortality from all causes in the population living in Spain.
Structural Changes Induced by Resveratrol in Monounsaturated and Polyunsaturated Phosphatidylcholine-Enriched Model Membranes
Authors: Hazarosova Rusina , Momchilova Albena , Vitkova Victoria , Yordanova Vesela , Kostadinova Aneliya , Angelova Miglena I. , Tessier Cedric , Nuss Philippe , Staneva Galya
Published: December 2023

Resveratrol (Resv) is considered to exert a beneficial impact due to its radical scavenger, anti-microbial and anti-inflammatory properties through several mechanisms that could include its interaction with the cell plasma membrane. To address this issue, we investigated the influence of Resv on membrane lipid order and organization in large unilamellar vesicles composed of different lipids and ratios. The studied lipid membrane models were composed of phosphatidylcholine (PC) species (either palmitoyl-docosahexaenoyl phosphatidylcholine (PDPC) or palmitoyl-oleoyl phosphatidylcholine (POPC)), sphingomyelin (SM) and cholesterol (Chol). This study found that the addition of Resv resulted in complex membrane reorganization depending on the degree of fatty acid unsaturation at the sn-2 position, and the Lipid/Resv and SM/Chol ratios. Resv rigidified POPC-containing membranes and increased liquid-ordered (Lo) domain formation in 40/40/20 POPC/SM/Chol mixtures as this increase was lower at a 33/33/34 ratio. In contrast, Resv interacted with PDPC/SM/Chol mixtures in a bimodal manner by fluidizing/rigidifying the membranes in a dose-dependent way. Lo domain formation upon Resv addition occurred via the following bimodal mode of action: Lo domain size increased at low Resv concentrations; then, Lo domain size decreased at higher ones. To account for the variable effect of Resv, we suggest that it may act as a “spacer” at low doses, with a transition to a more “filler” position in the lipid bulk. We hypothesize that one of the roles of Resv is to tune the lipid order and organization of cell plasma membranes, which is closely linked to important cell functions such as membrane sorting and trafficking.
md_harmonize: A Python Package for Atom-Level Harmonization of Public Metabolic Databases
Authors: Jin Huan , Moseley Hunter N. B.
Published: December 2023

A major challenge to integrating public metabolic resources is the use of different nomenclatures by individual databases. This paper presents md_harmonize, an open-source Python package for harmonizing compounds and metabolic reactions across various metabolic databases. The md_harmonize package utilizes a neighborhood-specific graph coloring method for generating a unique identifier for each compound via atom identifiers based on a compound’s chemical structure. The resulting harmonized compounds and reactions can be used for various downstream analyses, including the construction of atom-resolved metabolic networks and models for metabolic flux analysis. Parts of the md_harmonize package have been optimized using a variety of computational techniques to allow certain NP-complete problems handled by the software to be tractable for these specific use-cases. The software is available on GitHub and through the Python Package Index, with end-user documentation hosted on GitHub Pages.
Sensors in the Detection of Abused Substances in Forensic Contexts: A Comprehensive Review
Authors: Rosendo Luana M. , Antunes Mónica , Simão Ana Y. , Brinca Ana Teresa , Catarro Gonçalo , Pelixo Rodrigo , Martinho João , Pires Bruno , Soares Sofia , Cascalheira José Francisco , Passarinha Luís , Rosado Tiago , Barroso Mário , Gallardo Eugenia
Published: December 2023

Forensic toxicology plays a pivotal role in elucidating the presence of drugs of abuse in both biological and solid samples, thereby aiding criminal investigations and public health initiatives. This review article explores the significance of sensor technologies in this field, focusing on diverse applications and their impact on the determination of drug abuse markers. This manuscript intends to review the transformative role of portable sensor technologies in detecting drugs of abuse in various samples. They offer precise, efficient, and real-time detection capabilities in both biological samples and solid substances. These sensors have become indispensable tools, with particular applications in various scenarios, including traffic stops, crime scenes, and workplace drug testing. The integration of portable sensor technologies in forensic toxicology is a remarkable advancement in the field. It has not only improved the speed and accuracy of drug abuse detection but has also extended the reach of forensic toxicology, making it more accessible and versatile. These advancements continue to shape forensic toxicology, ensuring swift, precise, and reliable results in criminal investigations and public health endeavours.
Semi-Quantitative Analyses of Ferromanganese Nodules from the Pacific Ocean Using Synchrotron X-ray Powder Diffraction
Authors: Jung Jaewoo , Lee Soojin , Yang Kiho , Kim Jonguk , Hyeong Kiseong , Ko Youngtak , An Hyeonho , Park Jinsub , Seoung Donghoon , Lee Yongmoon
Published: December 2023

The geochemistry and mineralogy of Mn nodules offer crucial insights into the origins, environmental changes, and distribution of abyssal resources. However, the conventional laboratory X-ray diffractometer, usually employed for semi-quantitative analysis of mineral composition in Mn nodules, often fails to sufficiently detect minor phases due to beam flux limitations and high background signals. In this study, we investigated differences in manganate composition, even when comprising around 1% of the phase fraction, in two manganese nodules (KC-8 and KODOS-10) using high-resolution synchrotron X-ray diffraction. The Mn/Fe ratios of KC-8 and KODOS-10 were 1.32 and 6.24, respectively, indicating that KC-8 and KODOS-10 were predominantly formed in hydrogenetic and diagenetic environments. Both samples contained quartz, vernadite, buserite, and feldspar. Todorokite and illite were exclusively observed in KODOS-10. In KC-8, the phase fractions of vernadite and buserite among manganates ranged from 94(5)%–100(4)% and 6(1)%–0%, respectively. However, in KODOS-10, the fractions of vernadite, buserite, and todorokite ranged from 47(1)%–56(2)%, 33.6(4)%–40.1(3)%, and 10(3)%–16.3(8)%, respectively.
Sex-Related Differences of Weight Bearing and Non-Weight Bearing Muscle Properties
Authors: Nabavizadeh Omid , Herda Ashley A.
Published: December 2023

This study evaluated muscle composition, quality, and strength of non-weight bearing and weight bearing muscles between males and females. Twenty-eight, healthy males (n = 14; mean ± SD; age = 25.1 ± 4.2 years; height = 181.9 ± 10.6 cm; weight = 91.6 ± 17.2 kg) and females (n = 14; age = 25.0 ± 3.4 years; height = 165.9 ± 6.9 cm; weight = 66.0 ± 10.2 kg) underwent body composition assessment to estimate body fat (%BF) and total-body, arm, and leg fat-free mass (TFFM, ArmFFM, and LegFFM, respectively) and muscle composition via B-mode ultrasound to measure muscle cross-sectional area (mCSA), echo intensity (EI), and thickness (mT) of four muscles [rectus femoris (RF), vastus lateralis (VL), flexor digitorum superficialis (FDS), and flexor carpi radialis (FCR)]. Additionally, upper- [handgrip strength (HG)] and lower-body [leg extension (LE)] maximal strength were measured, recorded, and expressed relative to FFM to determine muscle quality (MQ) for the dominant arm and leg, respectively. Males had greater TFFM, ArmFFM, and LegFFM (p < 0.001), mCSA for RF, VL, FCR, and FDS (p < 0.001), and mT for RF, VL (p < 0.001–0.006). Females had greater EI for RF, VL, and FDS (p = 0.003–0.01). Negative correlations were identified between EI and MQ for all muscles in males and females, however, no significance was determined. Despite the sex differences in absolute strength and size, muscle quality (relative strength) was not different for the upper nor lower body.
Upscale Synthesis of Magnetic Mesoporous Silica Nanoparticles and Application to Metal Ion Separation: Nanosafety Evaluation
Authors: Ménard Mathilde , Ali Lamiaa M. A. , Vardanyan Ani , Charnay Clarence , Raehm Laurence , Cunin Frédérique , Bessière Aurélie , Oliviero Erwan , Theodossiou Theodossis A. , Seisenbaeva Gulaim A. , Gary-Bobo Magali , Durand Jean-Olivier
Published: December 2023

The synthesis of core–shell magnetic mesoporous nanoparticles (MMSNs) through a phase transfer process is usually performed at the 100–250 mg scale. At the gram scale, nanoparticles without cores or with multicore systems are observed. Iron oxide core nanoparticles (IO) were synthesized through a thermal decomposition procedure of α-FeO(OH) in oleic acid. A phase transfer from chloroform to water was then performed in order to wrap the IO nanoparticles with a mesoporous silica shell through the sol–gel procedure. MMSNs were then functionalized with DTPA (diethylenetriaminepentacetic acid) and used for the separation of metal ions. Their toxicity was evaluated. The phase transfer procedure was crucial to obtaining MMSNs on a large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. The homogeneous dispersion of MMSNs on the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPAs were shown to have a strong affinity for Ni ions. Furthermore, toxicity was evaluated in cells, zebrafish and seahorse cell metabolic assays, and the nanoparticles were found to be nontoxic. We developed a method of preparing MMSNs at the gram scale. After functionalization with DTPA, the nanoparticles were efficient in metal ion removal and separation; furthermore, no toxicity was noticed up to 125 µg mL−1 in zebrafish.
Barrier Height, Ideality Factor and Role of Inhomogeneities at the AlGaN/GaN Interface in GaN Nanowire Wrap-Gate Transistor
Authors: Mallem Siva Pratap Reddy , Puneetha Peddathimula , Choi Yeojin , Baek Seung Mun , Lee Dong-Yeon , Im Ki-Sik , An Sung Jin
Published: December 2023

It is essential to understand the barrier height, ideality factor, and role of inhomogeneities at the metal/semiconductor interfaces in nanowires for the development of next generation nanoscale devices. Here, we investigate the drain current (Ids)–gate voltage (Vgs) characteristics of GaN nanowire wrap-gate transistors (WGTs) for various gate potentials in the wide temperature range of 130–310 K. An anomalous reduction in the experimental barrier height and rise in the ideality factor with reducing the temperature have been perceived. It is noteworthy that the variations in barrier height and ideality factor are attributed to the spatial barrier inhomogeneities at the AlGaN/GaN interface in the GaN nanowire WGTs by assuming a double Gaussian distribution of barrier heights at 310–190 K (distribution 1) and 190–130 K (distribution 2). The standard deviation for distribution 2 is lower than that of distribution 1, which suggests that distribution 2 reflects more homogeneity at the AlGaN/GaN interface in the transistor’s source/drain regions than distribution 1.
70th Year Anniversary of Carbon Nanotube Discovery—Focus on Real-World Solutions
Authors: Paramsothy Muralidharan
Published: December 2023

Seventy years ago in 1952, Russian scientists LV Radushkevich and VM Lukyanovich published clear images showing multiwalled carbon nanotubes (MWCNTs) with 50 nm diameters [...]
Exploring the Potential of siRNA Delivery in Acute Myeloid Leukemia for Therapeutic Silencing
Authors: Ubeda Gutierrez Anyeld M. , Remant Bahadur K. C. , Brandwein Joseph , Uludağ Hasan
Published: December 2023

We investigated the feasibility of using siRNA therapy for acute myeloid leukemia (AML) by developing macromolecular carriers that facilitated intracellular delivery of siRNA. The carriers were derived from low-molecular-weight (<2 kDa) polyethyleneimine (PEI) and modified with a range of aliphatic lipids. We identified linoleic acid and lauric acid-modified PEI as optimal carriers for siRNA delivery to AML cell lines KG1 and KG1a, as well as AML patient-derived mononuclear cells. As they have been proven to be potent targets in the treatment of AML, we examined the silencing of BCL2L12 and survivin and showed how it leads to the decrease in proliferation of KG1 and stem-cell-like KG1a cells. By optimizing the transfection schedule, we were able to enhance the effect of the siRNAs on proliferation over a period of 10 days. We additionally showed that with proper modifications of PEI, other genes, including MAP2K3, CDC20, and SOD-1, could be targeted to decrease the proliferation of AML cells. Our studies demonstrated the versatility of siRNA delivery with modified PEI to elicit an effect in leukemic cells that are difficult to transfect, offering an alternative to conventional drugs for more precise and targeted treatment options.
Review of Piezoelectric Properties and Power Output of PVDF and Copolymer-Based Piezoelectric Nanogenerators
Authors: Bhadwal Neelesh , Ben Mrad Ridha , Behdinan Kamran
Published: December 2023

The highest energy conversion efficiencies are typically shown by lead-containing piezoelectric materials, but the harmful environmental impacts of lead and its toxicity limit future use. At the bulk scale, lead-based piezoelectric materials have significantly higher piezoelectric properties when compared to lead-free piezoelectric materials. However, at the nanoscale, the piezoelectric properties of lead-free piezoelectric material can be significantly larger than the bulk scale. The piezoelectric properties of Poly(vinylidene fluoride) (PVDF) and Poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) lead-free piezoelectric nanomaterials are reviewed and their suitability for use in piezoelectric nanogenerators (PENGs) is determined. The impact of different PVDF/PVDF-TrFE composite structures on power output is explained. Strategies to improve the power output are given. Overall, this review finds that PVDF/PVDF-TrFE can have significantly increased piezoelectric properties at the nanoscale. However, these values are still lower than lead-free ceramics at the nanoscale. If the sole goal in developing a lead-free PENG is to maximize output power, lead-free ceramics at the nanoscale should be considered. However, lead-free ceramics are brittle, and thus encapsulation of lead-free ceramics in PVDF is a way to increase the flexibility of these PENGs. PVDF/PVDF-TrFE offers the advantage of being nontoxic and biocompatible, which is useful for many applications.
Low Carbohydrate, High Fat Diet Alters the Oral Microbiome without Negating the Nitrite Response to Beetroot Juice Supplementation
Authors: Cato Louise E. , McKay Alannah K. A. , L’Heureux Joanna E. , Vanhatalo Anni , Jones Andrew M. , Askew Christopher D. , Slater Gary J. , Burke Louise M.
Published: December 2023

A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary nitrate supplementation can improve exercise economy via an increase in nitric oxide production, which is initiated by the reduction of nitrate to nitrite within the oral cavity. This reaction is dependent on the presence of nitrate-reducing oral bacteria, which can potentially be altered by dietary changes, including a LCHF diet. This study explored the effect of a LCHF diet on the oral microbiome and subsequent changes to plasma nitrite concentration following nitrate supplementation. Following five days of LCHF or high carbohydrate (HCHO) control dietary intervention, highly trained male race walkers consumed 140 mL beetroot juice containing 8.4 mmol nitrate; they then provided (a) blood samples for plasma nitrate and nitrite analysis and (b) saliva samples for 16S rRNA sequencing of the oral microbiome. The LCHF diet (n = 13) reduced oral bacterial diversity and changed the relative abundance of the genera Neisseria (+10%), Fusobacteria (+3%), Prevotella (−9%), and Veillonella (−4%), with no significant changes observed following the HCHO diet (n = 11). Following beetroot juice ingestion, plasma nitrite concentrations were higher for the LCHF diet compared to the HCHO diet (p = 0.04). However, the absence of an interaction with the trial (pre–post) (p = 0.71) suggests that this difference was not due to the dietary intervention. In summary, we found an increase in plasma nitrate and nitrite concentrations in response to nitrate supplementation independent of diet. This suggests the oral microbiome is adaptive to dietary changes and can maintain a nitrate reduction capacity despite a decrease in bacterial diversity following the LCHF diet.
The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review
Authors: Souza Ana , Vasconcelos Andrea , Dias Denise , Komoni Geovana , Name José
Published: December 2023

Aging is characterized by significant physiological changes, with the degree of decline varying significantly among individuals. The preservation of intrinsic capacity over the course of an individual’s lifespan is fundamental for healthy aging. Locomotion, which entails the capacity for independent movement, is intricately connected with various dimensions of human life, including cognition, vitality, sensory perception, and psychological well-being. Notably, skeletal muscle functions as a pivotal nexus within this intricate framework. Any perturbation in its functionality can manifest as compromised physical performance and an elevated susceptibility to frailty. Magnesium is an essential mineral that plays a central role in approximately 800 biochemical reactions within the human body. Its distinctive physical and chemical attributes render it an indispensable stabilizing factor in the orchestration of diverse cellular reactions and organelle functions, thereby rendering it irreplaceable in processes directly impacting muscle health. This narrative review offers a comprehensive exploration of the pivotal role played by magnesium in maintaining skeletal muscle integrity, emphasizing the critical importance of maintaining optimal magnesium levels for promoting healthy aging.
Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions
Authors: Szabó Éva , Csölle Ildikó , Felső Regina , Kuellenberg de Gaudry Daniela , Nyakundi Patrick Nyamemba , Ibrahim Kazahyet , Metzendorf Maria-Inti , Ferenci Tamás , Lohner Szimonetta
Published: December 2023

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane’s risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI −0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI −0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI −6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.