bluuebunny/crossref_metadata_2025 huggingface dataset:
The Catastrophic Water Loss of Ancient Lake Prespa: A Chronicle of a Death Foretold
Authors: Trajkovski Dejan , Apostolova Nadezda
Published: November 2024

The Prespa–Ohrid lake system in the southwest Balkan region is the oldest permanent lake system in Europe and a global hotspot of biodiversity and endemism. Its smaller component, Lake Macro Prespa (or simply called Prespa), shared by North Macedonia, Albania and Greece has suffered a dramatic water-level fall (nearly 10 m since the 1950s). It was greater in the periods 1987–1993 and 1998–2004 and has further accelerated in the last 5 years. Analysis of satellite images (remote sensing) revealed that over the period 1984–2020 Prespa Lake lost 18.87 km2 of its surface (6.9% of its size, dropping from 273.38 km2 to 254.51 km2), with a decline in the volume of water estimated as about 54%, even reaching 56.8% in 2022. The environmental status of the lake has also been compromised and the process of its eutrophication is enhanced. The aim of this study is to summarize the current understanding of the diminishing trend in the water level and the factors that have contributed to it. The lake is highly sensitive to external impacts, including climate change, mainly restricted precipitation and increased water abstraction for irrigation. Importantly, nearly half of its outflow is through karst aquifers that feed Ohrid Lake. Of note, the hydrology and especially hydrogeology of the catchment has not been studied in sufficient detail and accurate data for the present state are missing, largely due to a lack of coordinated investigations by the three neighboring countries. However, recent estimation of the water balance of Prespa Lake, elaborated with the consideration of only the natural sources of inflow (precipitation and river runoff) and outflow (evaporation and loss of water through the karst channels) suggested a negative balance of 53 × 106 m3 annually. Our study also offers an estimated projection for the water level in the future in different climate scenarios based on linear regression models that predict its complete loss before the end of the present century.
A Snapshot of Peer Relationships in Children and Youth: Pre- Versus During COVID-19
Authors: Manis Jordyn , Stewart Shannon L.
Published: November 2024

Strong peer relationships are an essential component of a healthy, happy, and long lifetime. Given that there is little understanding of the impact of COVID-19 on peer relationships, this study explored the effects of the COVID waves on peer relationships for clinically referred children and youth while controlling for age, sex, and income. 11,281 children and youth between the ages of 4 and 18 years, who were receiving services from mental health agencies across Ontario from January 2018–March 2022, were assessed using the interRAI ChYMH. Chi-square tests of independence and logistic regression analysis was performed. Overall, as expected, there were significantly fewer peer relationship difficulties during COVID-19 compared to the pre-pandemic period. Despite the general decline of peer issues, individuals between the ages of 8–18, particularly males, were more likely to experience peer relationship difficulties compared to those 4–7 years old. Additionally, children from the lowest income households experienced greater peer relationship difficulties during COVID-19 when compared to those from the highest income households. The findings from this study demonstrate the nuanced changes in social behaviours due to the ongoing pandemic for children and youth and highlight those youth who are most in need of social and behavioural interventions.
Special Issue “Transcriptomics in the Study of Insect Biology”
Authors: Dunaevsky Yakov E. , Elpidina Elena N.
Published: November 2024

Transcriptomics is at the intersection of molecular biology and genetics, and studies the complete set of transcripts that are synthesized in a cell or organism under certain conditions [...]
DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia
Authors: Nisar Hasan , Brauny Melanie , Labonté Frederik M. , Schmitz Claudia , Konda Bikash , Hellweg Christine E.
Published: November 2024

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O2, 48 h) p53 null H358 NSCLC cells after X-ray exposure. We used the colony-forming ability assay to determine cell survival, γH2AX immunofluorescence microscopy to quantify DNA double-strand breaks (DSBs), flow cytometry of DAPI-stained cells to measure cell cycle distribution, ELISAs to quantify IL-6 and IL-8 secretion in cell culture supernatants, and RNA sequencing to determine gene expression. Chronic hypoxia increased the colony-forming ability and radioresistance of H358 cells. It did not affect the formation or resolution of X-ray-induced DSBs. It reduced the fraction of cells undergoing G2 arrest after X-ray exposure and delayed the onset of G2 arrest. Hypoxia led to an earlier enhancement in cytokines secretion rate after X-irradiation compared to normoxic controls. Gene expression changes were most pronounced after the combined exposure to hypoxia and X-rays and pertained to senescence and different cell death pathways. In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.
Features of Highly Homologous T-Cell Receptor Repertoire in the Immune Response to Mutations in Immunogenic Epitopes
Authors: Zornikova Ksenia , Dianov Dmitry , Ivanova Natalia , Davydova Vassa , Nenasheva Tatiana , Fefelova Ekaterina , Bogolyubova Apollinariya
Published: November 2024

CD8+ T-cell immunity, mediated through interactions between human leukocyte antigen (HLA) and the T-cell receptor (TCR), plays a pivotal role in conferring immune memory and protection against viral infections. The emergence of SARS-CoV-2 variants presents a significant challenge to the existing population immunity. While numerous SARS-CoV-2 mutations have been associated with immune evasion from CD8+ T cells, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored, particularly for epitope-specific repertoires characterized by common TCRs. In this study, we investigated an HLA-A*24-restricted NYN epitope (Spike448-456) that elicits broad and highly homologous CD8+ T cell responses in COVID-19 patients. Eleven naturally occurring mutations in the NYN epitope, all of which retained cell surface presentation by HLA, were tested against four transgenic Jurkat reporter cell lines. Our findings demonstrate that, with the exception of L452R and the combined mutation L452Q + Y453F, these mutations have minimal impact on the avidity of recognition by NYN peptide-specific TCRs. Additionally, we observed that a similar TCR responded differently to mutant epitopes and demonstrated cross-reactivity to the unrelated VYF epitope (ORF3a112-120). The results contradict the idea that immune responses with limited receptor diversity are insufficient to provide protection against emerging variants.
Magnesium (Mg) and Neurodegeneration: A Comprehensive Overview of Studies on Mg Levels in Biological Specimens in Humans Affected Some Neurodegenerative Disorders with an Update on Therapy and Clinical Trials Supplemented with Selected Animal Studies
Authors: Ścibior Agnieszka , Llopis Juan , Dobrakowski Paweł P. , Męcik-Kronenberg Tomasz
Published: November 2024

Neurodegenerative diseases, characterized by neuron loss, are a group of neurological disorders that adversely affect the lives of millions of people worldwide. Although several medicines have been approved for managing neurodegenerative diseases, new therapies allowing for a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Magnesium (Mg), a crucial mineral necessary for the functioning of organisms, is important to normal central nervous system (CNS) activity. Although the effects of this bioelement on the CNS are relatively well recognized, its role in the pathophysiology of neurological disorders in humans is not yet well characterized. Therefore, the main goal of this review is to collect data about a possible association between Mg and neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s Disease (PD), and Amyotrophic lateral sclerosis (ALS) in humans. Hence, the levels of Mg in blood, cerebrospinal fluid (CSF), urine, and hair from subjects with AD, PD, and ALS are compiled to detect possible variations in the levels of this mineral in the biological specimens of people with neurodegenerative illnesses. Additionally, the findings from an animal model are summarized to offer the reader a deeper insight into studies on Mg in the context of neuroprotection and neurodegeneration. Data provided in the present review indicate that Mg, due to its neuroprotective, antioxidant, anti-inflammatory, and mitochondrial-supportive properties, could be a potential therapeutic agent for AD, PD, and ALS. However, more epidemiological studies with standardized methods of dietary assessment and Mg measurement are necessary to recognize its exact role in neurodegenerative disorders. Moreover, extensive well-designed clinical trials are also needed to establish definitive therapeutic protocols and optimal dosages, and to ensure long-term safety of this mineral supplementation in AD, PD, and ALS patients.
Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T+Itpr3tf/J
Authors: Cominelli Giorgia , Lonati Claudio , Pinto Daniela , Rinaldi Fabio , Franco Caterina , Favero Gaia , Rezzani Rita
Published: November 2024

Autism spectrum disorders (ASDs) are a pool of neurodevelopment disorders in which social impairment is the main symptom. Presently, there are no definitive medications to cure the symptoms but the therapeutic strategies that are taken ameliorate them. The purpose of this study was to investigate the effects of melatonin (MLT) in treating ASDs using an autistic mouse model BTBR T+Itpr3tf/J (BTBR). We evaluated the hepatic cytoarchitecture and some markers of autophagy, ferritinophagy/ferroptosis, in BTBR mice treated and not-treated with MLT. The hepatic morphology and the autophagy and ferritinophagy/ferroptosis pathways were analyzed by histological, immunohistochemical, and Western blotting techniques. We studied p62 and microtubule-associated protein 1 light chain 3 B (LC3B) for evaluating the autophagy; nuclear receptor co-activator 4 (NCOA4) and long-chain-coenzyme synthase (ACSL4) for monitoring ferritinophagy/ferroptosis. The liver of BTBR mice revealed that the hepatocytes showed many cytoplasmic inclusions recognized as Mallory–Denk bodies (MDBs); the expression and levels of p62 and LC3B were downregulated, whereas ACSL4 and NCOA4 were upregulated, as compared to control animals. MLT administration to BTBR mice ameliorated liver damage and reduced the impairment of autophagy and ferritinophagy/ferroptosis. In conclusion, we observed that MLT alleviates liver damage in BTBR mice by improving the degradation of intracellular MDBs, promoting autophagy, and suppressing ferritinophagy/ferroptosis.
Root-Knot Nematode Early Infection Suppresses Immune Response and Elicits the Antioxidant System in Tomato
Authors: Molinari Sergio , Farano Anna Carla , Leonetti Paola
Published: November 2024

The immune response in plants is regulated by several phytohormones and involves the overexpression of defense genes, including the pathogenesis-related (PR-) genes. The data reported in this paper indicate that nematodes can suppress the immune response by inhibiting the expression of defense genes. Transcripts from nine defense genes were detected by qRT-PCR in the roots of tomato plants at three and seven days post-inoculation (dpi) with living juveniles (J2s) of Meloidogyne incognita (root-knot nematodes, RKNs). All the salicylic acid (SA)-responsive genes tested (PR-1, PR-2, PR-4b, PR-5) were down-regulated in response to nematode infection. On the contrary, the expression of jasmonic acid (JA)-responsive genes, including ACO (encoding the enzyme 1-aminocyclopropane-1-carboxylic acid oxidase, which catalyzes the last step of ethylene (ET) biosynthesis) and JERF3 (Jasmonate Ethylene Response Factor 3), was unaffected by the infection. Conversely, the effect of nematode attack on the activities of the defense enzymes endoglucanase and endochitinase, encoded by PR-2 and PR-3, respectively, changed depending on the tested dpi. At 5 dpi, both enzymes were inhibited in inoculated plants compared to healthy controls. The genes encoding glutathione peroxidase (GPX) and catalase (CAT), both part of the antioxidant plant system, were highly overexpressed. Additionally, the activity of the antioxidant enzymes superoxide dismutase (SOD), CAT, and ascorbate peroxidase (APX) was enhanced in infected roots. Isoelectrofocusing of root extracts revealed novel SOD isoforms in samples from inoculated plants. Furthermore, plants were pre-treated with an array of key compounds, including hormone generators, inhibitors of SA or JA-mediated defense pathways, reactive oxygen species (ROS) scavengers and generators, inhibitors of ROS generation, and compounds that interfere with calcium-mediated metabolism. After treatments, plants were inoculated with RKNs, and nematodes were allowed to complete their life cycle. Factors of plant growth and infection level in treated plants were compared with those from untreated inoculated plants. Generally, compounds that decreased SA and/or ROS levels increased infection severity, while those that reduced JA/ET levels did not affect infection rates. ROS generators induced resistance against the pests. Compounds that silence calcium signaling by preventing its intake augmented infection symptoms. The data shown in this paper indicate that SA-mediated plant immune responses are consistently suppressed during the early stages of nematode infection, and this restriction is associated with the activation of the antioxidant ROS-scavenging system.
PPIA-coExp: Discovering Context-Specific Biomarkers Based on Protein–Protein Interactions, Co-Expression Networks, and Expression Data
Authors: Yan Dongsheng , Fan Zhiyu , Li Qianzhong , Chen Yingli
Published: November 2024

Identifying a small set of effective biomarkers from multi-omics data is important for the discrimination of different cell types and helpful for the early detection diagnosis of complex diseases. However, it is challenging to identify optimal biomarkers from the high throughput molecular data. Here, we present a method called protein–protein interaction affinity and co-expression network (PPIA-coExp), a linear programming model designed to discover context-specific biomarkers based on co-expressed networks and protein–protein interaction affinity (PPIA), which was used to estimate the concentrations of protein complexes based on the law of mass action. The performance of PPIA-coExp excelled over the traditional node-based approaches in both the small and large samples. We applied PPIA-coExp to human aging and Alzheimer’s disease (AD) and discovered some important biomarkers. In addition, we performed the integrative analysis of transcriptome and epigenomic data, revealing the correlation between the changes in gene expression and different histone modification distributions in human aging and AD.
Mast Cells in Allergic and Non-Allergic Upper Airways Diseases: Sentinel in the Watchtower
Authors: Costanzo Giovanni , Marchetti Marta , Ledda Andrea Giovanni , Sambugaro Giada , Bullita Martina , Paoletti Giovanni , Heffler Enrico , Firinu Davide , Costanzo Giulia Anna Maria Luigia
Published: November 2024

Mast cells are immune system cells with the most disparate functions, but are also among the least understood. Mast cells are implicated in several known pathological processes, tissue homeostasis, and wound repair. However, they owe their notoriety to allergic diseases, of which they represent the effector cell par excellence. In both allergic and not upper airway pathologies, mast cells play a key role. Exploring the mechanisms through which these cells carry out their physiological and pathological function may help us give a new perspective on existing therapies and identify new ones. A focus will be placed on non-allergic rhinitis, a poorly recognized and often neglected condition with complex management, where the role of the mast cell is crucial in the pathogenetic, clinical, and prognostic aspects.
1-Butyl-3-methylimidazolium-Based Ionic Liquid in Biomass Fractionation—Green Solvent or Active Reagent Toward Lignin Compounds?
Authors: Belesov Artyom V. , Mazur Dmitrii M. , Faleva Anna V. , Varsegov Ilya S. , Pikovskoi Ilya I. , Ulyanovskii Nikolay V. , Kosyakov Dmitry S.
Published: November 2024

N,N′-Dialkylimidazolium-based ionic liquids are capable of completely dissolving lignocellulosic biomass at elevated temperatures and are considered as promising green solvents for future biorefining technologies. However, the obtained ionic liquid lignin preparations may contain up to several percent nitrogen. This indicates strong interactions between the biopolymer and the IL cation, the nature of which has not yet been clarified. The present study investigates mechanisms and pathways of the formation of nitrogen-containing lignin compounds. To achieve this goal, eight monomeric lignin-related phenols bearing different functional groups (ketone, aldehyde, hydroxyl, carbon–carbon double bonds) were treated with 1-butyl-3-methylimidazolium acetate (BmimOAc) under typical conditions of IL-assisted lignocellulose fractionation (80–150 °C). A number of the resulting products were tentatively identified, for all the studied model compounds, by two-dimensional NMR spectroscopy and high-performance liquid chromatography—high-resolution mass spectrometry. They all possess covalently bonded Bmim residues and occur through the nucleophilic addition of an N-heterocyclic carbene (deprotonated Bmim cation) to electron-deficient groups. The reactivity of lignin functional groups in their interaction with Bmim is greatly affected by the temperature and dissolved oxygen. IL’s thermal degradation products act as additional reactive species toward lignin, further complicating the range of products formed. The obtained results made it possible to answer the question posed in this article’s title and to assert that N,N′-dialkylimidazolium-based ILs act as active reagents with respect to lignin during the dissolution of lignocellulose.
Periodontal Molecular Diagnostics: State of Knowledge and Future Prospects for Clinical Application
Authors: Dolińska Ewa , Wiśniewski Patryk , Pietruska Małgorzata
Published: November 2024

Periodontitis leads to immunologically mediated loss of periodontium and, if untreated, can result in tooth loss. Periodontal diseases are the most prevalent in the world and have a very strong impact on patients’ well-being and general health. Their treatment generates enormous costs. Given the above, precise, prompt, and predictive diagnosis of periodontal disease is of paramount importance for clinicians. The aim of the study was to summarize the state-of-the-art knowledge of molecular periodontal diagnostics and the utility of its clinical application. There is a great need to have diagnostic tests that not only describe the periodontal destruction that has occurred in the tissues but also allow clinicians to detect disease at a subclinical level before the changes occur. A test that would enable clinicians to follow the course of the disease and detect areas prone to exacerbation could be used to evaluate the effectiveness of ongoing periodontal therapies. Unfortunately, there is no such diagnostic method yet. A hopeful prospect is molecular diagnostics. There are numerous studies on biomarkers of periodontal disease. Point-of-care tests are also emerging. There are possibilities for processing large biological datasets (omics data). However, all of the above have a minor role in the overall single-patient diagnostics process. Despite advances in microbiological, molecular, and genetic research, the basis of periodontal diagnosis is still clinical examination enriched by the evaluation of radiological images.
Mesenchymal Stem Cell-Exosomal miR-99a Attenuate Silica-Induced Lung Fibrosis by Inhibiting Pulmonary Fibroblast Transdifferentiation
Authors: Hao Xiaohui , Li Peiyuan , Wang Yudi , Zhang Qinxin , Yang Fang
Published: November 2024

Silicosis is one of the most prevalent and fatal occupational diseases worldwide, with unsatisfactory clinical outcomes. This study aimed to investigate the therapeutic effect and related molecular mechanisms of how mesenchymal stem cell (MSC)-secreted exosomes alleviate SiO2-induced pulmonary fibrosis. miR-99a-5p was significantly downregulated in silicosis models via high-throughput miRNA screening, and was overlapped with miRNAs in exosomes from MSCs. miR-99a-5p was significantly downregulated in the lung of a mice silicosis model and in TGFβ1-induced NIH-3T3 cells. In contrast, fibroblast growth factor receptor 3 (FGFR3), a direct target gene of miR-99a-5p, was upregulated in vitro and in vivo. Furthermore, we demonstrated that MSC-derived exosomes deliver enriched miR-99a-5p to target cells and inhibit TGF-β1-induced fibroblast transdifferentiation to reduce collagen protein production. Similarly, in a silicosis mouse model, MSC-derived exosome treatment through the tail veins of the mice counteracted the upregulation of fibrosis-related proteins and collagen deposition in the lung of the mice. By constructing exosomal therapeutic cell models with different miR-99a expressions, we further demonstrated that miR-99a-5p might attenuate pulmonary fibrosis by regulating target protein FGFR3 and downstream mitogen-activated protein kinase (MAPK) signalling pathways. Our study demonstrated that MSC-derived exosomes ameliorate SiO2-induced pulmonary fibrosis by inhibiting fibroblast transdifferentiation and represent an attractive method of pulmonary fibrosis treatment.
Albumin Is an Integrative Protein of Blood Plasma and Beyond
Authors: Belinskaia Daria A. , Jenkins Richard O. , Goncharov Nikolay V.
Published: November 2024

Albumin is a major protein in mammalian blood plasma or serum, where its concentration in healthy organisms is about 600 μM [...]
Anisotropy in Carbon Dioxide Adsorption on Forsterite
Authors: Ermolov Yakov , Vasilchenko Andrey , Lazorenko Georgy
Published: November 2024

In this study, density functional theory (DFT) method were used to investigate the adsorption behavior and binding mechanism of CO2 molecules on six crystallographic surfaces of forsterite (Mg2SiO4). The influence of surface crystallographic orientation on CO2 adsorption efficiency was examined at the atomic level. Results showed stable binding of CO2 on all surfaces. The interaction strength decreases in the order: (001) > (101) > (120) > (111) > (010) > (110), with the (001) surface exhibiting the highest binding capacity due to accessible magnesium cations interacting with CO2. Detailed electronic property analysis revealed significant charge transfer between CO2 oxygen atoms and surface magnesium atoms, driven by hybridization of oxygen 2p and magnesium 2s orbitals, leading to the formation of ionic and covalent bonds. These interactions stabilize the adsorbed CO2 and are accompanied by changes in the electronic structure, such as energy level shifts and modifications in the partial density of states (PDOS). The computational analysis provides a theoretical foundation for understanding CO2 binding mechanisms by forsterite. The findings highlight the importance of crystallographic orientation and electronic properties of the mineral surface in adsorption efficiency, contributing to a deeper understanding of CO2 interactions with mineral surfaces.
Egg Cooling After Oviposition Extends the Permissive Period for Microinjection-Mediated Genome Modification in Bombyx mori
Authors: Uchino Keiro , Waizumi Ryusei , Sumitani Megumi , Sakai Hiroki , Yamada Nobuto , Kojima Katsura , Yonemura Naoyuki , Tatematsu Ken-Ichiro , Iizuka Tetsuya , Sezutsu Hideki , Tamura Toshiki
Published: November 2024

In general, transgenesis efficiency is largely dependent on the developmental status of eggs for microinjection. We investigated whether the relationship between transgenesis efficiency and cooling eggs in silkworms, Bombyx mori, affects the transgenesis frequencies. First, we performed a microinjection using eggs of different developmental statuses at 25 °C. As a result, the use of eggs at 4 h after egg-laying (hAEL) demonstrated nearly five times greater efficiency in frequency compared to 8 hAEL but no transgenesis was found at 12 hAEL. Second, we examined the use of eggs stored for 5 or 24 h at 10 °C. We found that transgenic silkworms were produced not only 5 hAEL but also 24 hAEL. Finally, in the BmBLOS2 gene knock-out experiment, eggs stored at 10 °C demonstrated knock-out phenotypes even 48 hAEL at the time of injection (G0). These results demonstrate that an egg cooling treatment enables drastically enhanced rates of efficiency for insect genome modification. Our results could be useful in other insects, especially species with an extremely short syncytial preblastodermal stage.
Potentiation of NMDA Receptors by AT1 Angiotensin Receptor Activation in Layer V Pyramidal Neurons of the Rat Prefrontal Cortex
Authors: Hanuska Adrienn , Ribiczey Polett , Kató Erzsébet , Papp Zsolt Tamás , Varga Zoltán V. , Giricz Zoltán , Tóth Zsuzsanna E. , Könczöl Katalin , Zsembery Ákos , Zelles Tibor , Harsing Laszlo G. , Köles László
Published: November 2024

NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions. Previous research has indicated that angiotensin II (Ang II) affects learning and memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer V pyramidal cells of the rat PFC. Whole-cell patch-clamp experiments were performed in pyramidal cells in brain slices of 9–12-day-old rats. NMDA (30 μM) induced inward currents. Ang II (0.001–1 µM) significantly enhanced NMDA currents in about 40% of pyramidal cells. This enhancement was reversed by the AT1 antagonist eprosartan (1 µM), but not by the AT2 receptor antagonist PD 123319 (5 μM). When pyramidal neurons were synaptically isolated, the increase in NMDA currents due to Ang II was eliminated. Additionally, the dopamine D1 receptor antagonist SCH 23390 (10 μM) reversed the Ang II-induced enhancement, whereas the D2 receptor antagonist sulpiride (20 μM) had no effect. The potentiation of NMDA currents in a subpopulation of layer V pyramidal neurons by Ang II, involving AT1 receptor activation and dopaminergic signaling, may serve as an underlying mechanism for the effects of the renin–angiotensin system (RAS) elements on neuronal functions.
Silver Nanoparticles (AgNPs) Incorporation into Polymethyl Methacrylate (PMMA) for Dental Appliance Fabrication: A Systematic Review and Meta-Analysis of Mechanical Properties
Authors: Galant Kacper , Turosz Natalia , Chęcińska Kamila , Chęciński Maciej , Cholewa-Kowalska Katarzyna , Karwan Sławomir , Chlubek Dariusz , Sikora Maciej
Published: November 2024

Polymethyl methacrylate (PMMA), widely used in orthodontics and dentures, exhibits suboptimal mechanical properties, including flexural strength (FS), impact strength (IS), and tensile strength (TS), which are critical for ensuring durability, resistance to fracture, and overall functionality of dental appliances. Silver nanoparticles (AgNPs) are a promising filler due to their antimicrobial properties. This pre-registered (osf.io/yqftx) PRISMA-compliant meta-analysis compared the mechanical properties of PMMA/AgNP composites to pure PMMA, considering mean particle size and concentration. Of 360 records from ACM, BASE, PubMed, and Scopus, 35 studies were included (κ = 0.91), covering 88, 38, and 11 tests on FS, IS, and TS, respectively. FS increased only between 30–70 nm (r = 0.00; ρ = 0.03; R2deg2 = 0.13). IS remained higher for <80 nm and increased between 15 and 25 nm (r = −0.41; ρ = −0.28; R2deg2 = 0.59). TS favored 55 nm but had limited data (r = −0.24; ρ = 0.63; R2deg2 = 0.99). FS decreased with increasing wt%, showing no discernible trend (r = −0.22; ρ = −0.34). IS increased within 0.0–4.0 wt%, particularly 0.5–2.0 wt% (r = −0.15; ρ = −0.35; R2deg2 = 0.54). TS peaked at 0.5–2.0 wt% (r = −0.20; ρ = −0.24; R2deg2 = 0.91). Optimal mechanical properties of PMMA/AgNP likely fall within 15–70 nm mean nanoparticle size and 0.5–4.0 wt% concentration.
Investigating the Role of Primary Cilia and Bone Morphogenetic Protein Signaling in Periodontal Ligament Response to Orthodontic Strain In Vivo and In Vitro: A Pilot Study
Authors: Moore Emily R. , Konermann Anna
Published: November 2024

Periodontal ligament (PDL) cells are crucial for mechanosensation and mechanotransduction within the PDL, yet the role of primary cilia in orthodontic force transmission has not been examined. While bone morphogenetic protein (BMP) signaling significantly influences ciliary function, its effect on cellular responses to mechanical stress has not been investigated. This study aims to investigate whether primary cilia and BMP signaling are involved in the periodontal ligament’s response to orthodontic tooth movement and the resultant mechanical strain. To visualize primary cilia, human PDL cells were cultured on glass-bottom dishes for five days, with a subset fixed daily, followed by immunostaining with anti-acetylated α-tubulin and Alexa Fluor 568 and imaging using a fluorescence microscope under 405 nm and 561 nm laser excitation. Human PDL cells were grown on Bioflex® culture plates and subsequently exposed to static tensile strains of 2.5%, 5%, 10%, 20%, on a FX-6000T™ Tension System for 24 h. RT-qPCR was performed to evaluate changes in expression of primary cilia via Ift88 expression, mechanotransduction via Cox2 expression, and BMP signaling-related genes. Histological specimens from orthodontically loaded and control human premolars were investigated for primary cilia and BMP signaling using immunohistochemistry and confocal microscopy. Primary cilia were observed in PDL cells from day one, with their incidence and length increasing over time alongside cell density. BMP signaling components, including upregulated genes such as Bmp7 (10.99–14.97 fold), Alk2 (3.19–5.45 fold), and Bmpr2 (1.64–8.40 fold), consistently responded to strain, while Cox2 and Ift88 showed differential regulation depending on strain intensity. In vivo, orthodontic movement activated BMP signaling and increased primary cilium incidence in the PDL. These findings indicate the potential role of primary cilia and BMP signaling in the mechanosensitivity of PDL cells under orthodontic forces. Further studies are required to understand the complex mechanotransduction mechanisms and role of these components in cellular adaptation during orthodontic tooth movement.
Backstage Heroes—Yeast in COVID-19 Research
Authors: Grabiński Wojciech , Karachitos Andonis , Kicińska Anna
Published: November 2024

The extremely rapid development of understanding and technology that led to the containment of the COVID-19 pandemic resulted from collaborative efforts in the fields of Betacoronavirus pandemicum (SARS-CoV-2) biology, pharmacology, vaccinology, and medicine. Perhaps surprisingly, much of the research was conducted using simple and efficient yeast models. In this manuscript, we describe how yeast, eukaryotic microorganisms, have been used to research this global challenge, focusing on the therapeutic potential of the studies discussed herein. Thus, we outline the role of yeast in studying viral protein interactions with the host cell proteome, including the binding of the SARS-CoV-2 virus spike protein to the human ACE2 receptor and its modulation. The production and exploration of viral antigens in yeast systems, which led to the development of two approved COVID-19 vaccines, are also detailed. Moreover, yeast platforms facilitating the discovery and production of single-domain antibodies (nanobodies) against SARS-CoV-2 are described. Methods guiding modern and efficient drug discovery are explained at length. In particular, we focus on studies designed to search for inhibitors of the main protease (Mpro), a unique target for anti-coronaviral therapies. We highlight the adaptability of the techniques used, providing opportunities for rapid modification and implementation alongside the evolution of the SARS-CoV-2 virus. Approaches introduced in yeast systems that may have universal potential application in studies of emerging viral diseases are also described.
Ganglioside GM1 Alleviates Propofol-Induced Pyroptosis in the Hippocampus of Developing Rats via the PI3K/AKT/NF-κB Signaling Cascade
Authors: Zhang Zhiheng , Du Shan , Chen Xinzhang , Qiu Di , Li Siyao , Han Lin , Bai Hui , Gao Ruifeng
Published: November 2024

In pediatric and intensive care units, propofol is widely used for general anesthesia and sedation procedures as a short-acting anesthetic. Multiple studies have revealed that propofol causes hippocampal injury and cognitive dysfunction in developing animals. As is known, GM1, a type of ganglioside, plays a crucial role in promoting nervous system development. Consequently, this study explored whether GM1 mitigated neurological injury caused by propofol during developmental stages and investigated its underlying mechanisms. Seven-day-old SD rats or PC12 cells were used in this study for histopathological analyses, a Morris water maze test, a lactate dehydrogenase release assay, Western blotting, and an ELISA. Furthermore, LY294002 was employed to explore the potential neuroprotective effect of GM1 via the PI3K/AKT signaling cascade. The results indicated that GM1 exerted a protective effect against hippocampal morphological damage and pyroptosis as well as behavioral abnormalities following propofol exposure by increasing p-PI3K and p-AKT expression while decreasing p-p65 expression in developing rats. Nevertheless, the inhibitor LY294002, which targets the PI3K/AKT cascade, attenuated the beneficial effects of GM1. Our study provides evidence that GM1 confers neuroprotection and attenuates propofol-induced developmental neurotoxicity, potentially involving the PI3K/AKT/NF-κB signaling cascade.
A Model to Strengthen the Quality of Midwifery Education: A Grounded Theory Approach
Authors: Ige Waleola B. , Ngcobo Winnie B.
Published: November 2024

A well-educated midwifery workforce is critical to providing quality health services. However, the quality of midwifery education in Nigeria is identified as a factor contributing to the country’s poor maternal and neonatal health outcomes and inability to meet global development goals. This study aimed to analyse the process used to strengthen the quality of midwifery education with the aim of generating a middle-range model to prepare competent and confident midwifery graduates. The Strauss and Corbin version of the Grounded Theory approach that is underpinned by the Social Constructivism Paradigm was adopted for this qualitative study. Strengthening the quality of midwifery education (SQME) emerged as the model’s core phenomenon. Major concepts, including the midwifery education context, nature of the curriculum, SQME process, pillars, and outcomes, supported the core phenomenon. Strengthening the quality of midwifery education can be achieved over a long time provided the pillars of SQME are deep-rooted to sustain the process of strengthening the quality of midwifery education. The model can be used to strengthen the quality of midwifery education and may be adapted to nursing/allied health programmes in Nigeria and other developing countries.
Integrating Digitalization and Asset Health Index for Strategic Life Cycle Cost Analysis of Power Converters
Authors: González-Prida Vicente , de la Fuente Carmona Antonio , Guillén López Antonio J. , Gómez Fernández Juan F. , Crespo Márquez Adolfo
Published: November 2024

In the context of energy storage systems, optimizing the life cycle of power converters is crucial for reducing costs, making informed decisions, and ensuring sustainability. This study presents a comprehensive methodology for calculating the life cycle cost (LCC) of power converters, employing a nine-step process that integrates digitalization, Internet of Things (IoT) technologies, and the Asset Health Index (AHI). The methodology adapts the Woodward model to provide a detailed cost analysis, encompassing the acquisition, operation, maintenance, and end-of-life phases. Our findings reveal significant insights into asset management, highlighting the importance of preventive and major maintenance in controlling failure rates and extending asset life. This study concludes that adopting sustainable business models and leveraging advanced technologies can enhance the reliability and maintainability of power converters, ultimately leading to more competitive and environmentally friendly energy storage solutions.
Preparation and Antifungal Properties of Cyclopropyl Derivatives of 3-Aminoquinazolin-4(3H)-one and Salicylal Schiff Base Nickel(II) Chelate Complex
Authors: Fedotov Alexander N. , Trofimova Elena V. , Tafeenko Victor A. , Gloriozov Igor P. , Mironov Andrey V. , Zakharov Alexandre N.
Published: November 2024

N-substituted 2-cyclopropyl-3-R-quinazoline-4()-ones [R: NH2 (1), N=CH(2-hydroxyphenyl) (2)] and Ni(II) chelate compound of 2-cyclopropyl-3-[(Z)-(2-hydroxybenzylidene)amino]quinazoline-4(3H)-one (3) were synthesized and their structures and properties were characterized using X-ray diffraction data, computational optimization, 1H and 13C NMR, IR spectroscopy, and diffuse reflectance spectra. Compounds 1 and 2 are monoclinic (space group P21/n). Unit cell parameters (a, b, c) are 9.2529; 4.7246; 22.3460 Å and 10.2811; 4.6959; 30.972 Å for 1 and 2, respectively. Nickel(II) chelate compound crystallizes in an orthorhombic crystal system (space group Pbca). Unit cell parameters (a, b, c) for 3 are 26.5010; 14.8791; 8.904975 Å, respectively. Schiff base 2 in the crystalline state exhibits two rotary isomers in a molar ratio of 1:3, among which only a minor component as a bidentate ligand can form compound 3 with Ni(II) ion. Nickel(II) ion in 3 is coordinated by N donor atoms and deprotonated O atoms of Schiff base ligands to form square-planar chelate node NiN2O2. All synthesized compounds revealed high antifungal activity against bread mold (Mucor mucedo).
Functional Role of Odorant-Binding Proteins in Response to Sex Pheromone Component Z8-14:Ac in Grapholita molesta (Busck)
Authors: Luo Yuqing , Chen Xiulin , Xu Shiyan , Li Boliao , Luo Kun , Li Guangwei
Published: November 2024

The plum fruit moth (PFM), Grapholita funebrana, and the oriental fruit moth (OFM), G. molesta, are closely related fruit moth species that severely damage fruit trees in Rosaceae. Both species share common primary sex pheromone components Z8-12:Ac and E8-12:Ac. The secondary sex pheromone components of PFMs consist of Z8-12:OH, Z8-14:Ac, and Z10-14:Ac, while those of OFMs include Z8-12:OH and 12:OH. Previous researchers have proved that the inclusion of Z8-14:Ac and Z10-14:Ac did not augment PFM catches but inhibited OFM catches in orchards in Europe, thereby maintaining the species-specificity of the PFM sex attractant. However, which of these components, Z8-14:Ac or Z10-14:Ac, plays the major role in inhibiting OFM attraction remains unclear. In the current study, electroantennogram (EAG) assays indicated that both OFM and PFM males exhibited a moderate EAG response to Z8-14:Ac and Z10-14:Ac. Rubber septa loaded with varying ratios of Z8-14:Ac (1% to 30%) or Z10-14:Ac (5% to 110%) combined with a constant dose of Z8-12:Ac and E8-12:Ac produced diverse trapping effects. Sex attractants containing Z8-14:Ac did not significantly affect the trapping of PFM males but drastically reduced the capture of OFM males, with the reduction reaching up to 96.54%. Attractants containing more than 10% of Z10-14:Ac simultaneously reduced the number of OFM and PFM males captured. Z8-14:Ac was indispensable for maintaining the specificity of sex pheromones. Fluorescence competitive binding assays of recombinant GmolPBP2 showed the lowest Ki value (0.66 ± 0.02 μM) among the PBPs/GOBPs from OFMs, suggesting that it is the most likely target for Z8-14:Ac. Molecular dynamic simulation and site-directed mutagenesis assays confirmed that the Phe12 residue, which forms a π–alkyl interaction with Z8-14:Ac, was crucial for GmolPBP2 binding to Z8-14:Ac. In conclusion, Z8-14:Ac is vital to the specificity of PFM sex pheromones inhibiting OFM attractants when added to Z8-12:Ac and E8-12:Ac. This could be potentially used to develop species-specific sex attractants for the PFM.
Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review
Authors: Patiño-Cardona Silvana , Garrido-Miguel Miriam , Pascual-Morena Carlos , Berlanga-Macías Carlos , Lucerón-Lucas-Torres Maribel , Alfaro-González Sofía , Martínez-García Irene
Published: November 2024

Coenzyme Q10 (CoQ10) has been suggested as an adjunct therapy for endocrine and metabolic disorders. The aim of this study was to synthesise the evidence for the effect of CoQ10 supplementation on lipid and/or glycaemic alterations, including total cholesterol (TC), LDL- and HDL-cholesterol (LDL-C and HDL-C), lipoprotein a, fasting blood glucose (FBG), haemoglobin A1c (HbA1c), fasting insulin and Homeostatic Model Assessment of Insulin Resistance. A systematic search was conducted in Medline, Scopus, Web of Science and the Cochrane Library from their inception to July 2024. Meta-analyses that evaluated the effect of CoQ10 on the lipid or glycaemic profiles were included. Results were expressed as mean difference (MD) or standardised mean difference (SMD). CoQ10 showed an effect on the glycaemic profile, especially on FBG (MD from −11.21 to −5.2 mg/dL, SMD from −2.04 to −0.17) and on HbA1c (MD from −1.83 to −0.12%, SMD of −0.30). CoQ10 may also have an effect on the lipid profile, such as TC, triglycerides, HDL-C and even LDL-C, although the inconsistency of the results was somewhat higher. Supplementation with CoQ10 may be beneficial, especially in populations with diabetes mellitus or other endocrine and metabolic disorders. It could also have some effect on lipid parameters, which, together with the above, may reduce cardiovascular morbidity and mortality, although this is something that needs further research.
The Predictive Power of the Transplant Evaluation Rating Scale (TERS) for Psychosocial Outcomes in Living-Donor Kidney Transplant Recipients: A Two-Year Prospective Study
Authors: Richter Ernst Peter , Schlegel Betty , Berth Hendrik
Published: November 2024

Background/Objectives: The Transplant Evaluation Rating Scale (TERS) assesses the psychosocial risk of transplant candidates; however, its predictive value for outcomes in living-donor kidney transplant (LDKT) recipients remains unclear. This study evaluated the predictive power of the TERS for psychosocial outcomes in LDKT recipients over two years post-transplant. Methods: In this prospective single-center cohort study, 107 LDKT recipients completed assessments pre-transplant (T0), 6 months post-transplant (T1), and 24 months post-transplant (T2). The outcomes measured were mental distress, physical complaints, and perceived social support. Linear mixed-effects models were used to examine the relationship between the pre-transplant TERS scores and outcomes over time. Results: Higher TERS scores predicted increased physical complaints (p < 0.001) and lower perceived social support (p = 0.035) at all time points. Additionally, higher TERS scores were associated with greater mental distress between T0 and T2 (p < 0.001). A hierarchical partitioning revealed that the TERS accounted for 11.9% of the variance in mental distress, 14.6% of that in physical complaints, and 6.0% of that in perceived social support. Conclusions: The pre-transplant psychosocial risk, as measured by the TERS, significantly predicted the psychosocial outcomes in the LDKT recipients over two years, with small-to-medium effect sizes. The TERS may serve as a valuable tool for identifying patients who could benefit from targeted psychosocial interventions to improve their long-term outcomes.
Association Between Longer Cecal Intubation Time and Detection and Miss Rate of Colorectal Neoplasms
Authors: Choi Ji Min , Lim Seon Hee , Han Yoo Min , Lee Jooyoung , Jin Eun Hyo , Seo Ji Yeon , Kim Jung
Published: November 2024

Background/Aims: A longer cecal intubation time (CIT) occurs during colonoscopy under difficult insertion conditions, which may hinder meticulous mucosal observation. However, whether a longer CIT has detrimental effects on the detection of adenomas remains unclear. We evaluated the effects of CIT on the detection and miss rates of colorectal neoplasms in asymptomatic participants. Methods: Healthy examinees who underwent colonoscopy between March and July 2011, August 2015, and December 2016 were retrospectively enrolled. The primary outcome was the adenoma detection rate (ADR) across CIT quartiles, while the secondary outcomes included the mean number of adenomas, advanced ADR (AADR), clinically significant serrated lesion (CSSP) detection, adenoma miss rate (AMR), miss rate of CSSPs and any colorectal neoplasms, and the mean number of missed colorectal neoplasms in relation to CIT. Results: Overall, 12,402 participants were classified into quartiles according to the CIT. The longer the CIT, the lower the ADR (p < 0.001), AADR (p = 0.004), and mean number of adenomas (p < 0.001). The CSSP detection rate was not associated with CIT. On follow-up colonoscopy, AMR showed marginal increase with longer CIT (p = 0.065). The missed rates of CSSPs (p = 0.002) and colorectal neoplasms (p = 0.001) also increased with longer CIT. In the multivariate analysis, CIT was significantly associated with ADR, AADR, and AMR. Conclusions: Longer CIT was associated with lower ADR and higher AMR. Meticulous inspection is important for high-quality colonoscopy, particularly in patients requiring a longer CIT.
Auto-Rad: End-to-End Report Generation from Lumber Spine MRI Using Vision–Language Model
Authors: Yeasin Mohammed , Moinuddin Kazi Ashraf , Havugimana Felix , Wang Lijia , Park Paul
Published: November 2024

Background: Lumbar spinal stenosis (LSS) is a major cause of chronic lower back and leg pain, and is traditionally diagnosed through labor-intensive analysis of magnetic resonance imaging (MRI) scans by radiologists. This study aims to streamline the diagnostic process by developing an automated radiology report generation (ARRG) system using a vision–language (VL) model. Methods: We utilized a Generative Image-to-Text (GIT) model, originally designed for visual question answering (VQA) and image captioning. The model was fine-tuned to generate diagnostic reports directly from lumbar spine MRI scans using a modest set of annotated data. Additionally, GPT-4 was used to convert semistructured text into coherent paragraphs for better comprehension by the GIT model. Results: The model effectively generated semantically accurate and grammatically coherent reports. The performance was evaluated using METEOR (0.37), BERTScore (0.886), and ROUGE-L (0.3), indicating its potential to produce clinically relevant content. Conclusions: This study highlights the feasibility of using vision–language models to automate report generation from medical imaging, potentially reducing the diagnostic workload for radiologists.