bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the Lake History of Taylor Valley, Antarctica During the Ross Sea I Glaciation
Authors: Stone Michael S. , Doran Peter T. , Myers Krista F.
Published: January 2025

The Ross Sea I glaciation, marked by the northward advance of the Ross Ice Sheet (RIS) in the Ross Sea, east Antarctica, corresponds with the last major expansion of the West Antarctic Ice Sheet during the last glacial period. During its advance, the RIS was grounded along the southern Victoria Land coast, completely blocking the mouths of several of the McMurdo Dry Valleys (MDVs). Several authors have proposed that very large paleolakes, proglacial to the RIS, existed in many of the MDVs. Studies of these large paleolakes have been key in the interpretation of the regional landscape, climate, hydrology, and glacier and ice sheet movements. By far the most studied of these large paleolakes is Glacial Lake Washburn (GLW) in Taylor Valley. Here, we present a comprehensive review of literature related to GLW, focusing on the waters supplying the paleolake, signatures of the paleolake itself, and signatures of past glacial movements that controlled the spatial extent of GLW. We find that while a valley-wide proglacial lake likely did exist in Taylor Valley during the early stages of the Ross Sea I glaciation, during later stages two isolated lakes occupied the eastern and western sections of the valley, confined by an expansion of local alpine glaciers. Lake levels above ~140 m asl were confined to western Taylor Valley, and major lake level changes were likely driven by RIS movements, with climate variables playing a more minor role. These results may have major implications for our understanding of the MDVs and the RIS during the Ross Sea I glaciation.
Antioxidative Effects of Curcumin on Erastin-Induced Ferroptosis Through GPX4 Signalling
Authors: Kose Tugba , Sharp Paul A. , Latunde-Dada Gladys O.
Published: January 2025

Background/Objectives: Pancreatic cancer is a common gastrointestinal cancer with high risk of mortality. Currently, the therapeutic strategies for pancreatic cancers are surgery, chemotherapy, and radiotherapy, none of which are effective treatments. Ferroptosis is a new form of cell death that is iron (Fe)-dependent and characterized by lipid peroxidation, which is a new approach for treatment of pancreatic cancer. Therefore, this study was dedicated to investigating the effect of erastin and Ras-selective lethal small molecule 3 (RLS3) as ferroptosis inducers as well as focusing on the antioxidant effects of two natural products, curcumin and (−)-epigallocatechin-3-gallate (EGCG), against ferroptosis. Methods: PANC1 cells were treated with 20 μmol/L curcumin or EGCG and then exposed to 20 μmol/L erastin. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, Reactive Oxygen Species (ROS) were measured by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, Fe levels were determined by inductively coupled plasma mass spectrometry (ICP-MS), and glutathione (GSH), lipid peroxidation, Western blot, and mRNA were assayed with commercially available kits. Results: Curcumin and EGCG enhanced cell viability in erastin-treated PANC1 cells in a dose-and time-dependent manner. Erastin-treated PANC1 cells exhibited the elevated levels of GSH depletion, ROS productions, and lipid peroxidation while curcumin reversed the erastin-induced ferroptotic effects. The treatment of erastin-induced PANC1 cells with curcumin increased the GPX4 mRNA gene and protein levels. Also, curcumin decreased the FTH1 mRNA gene levels as a strong Fe chelator. Conclusions: In conclusion, this study shows that erastin can be potentially a therapeutic strategy for treatment of cancer cells. Additionally, curcumin might play an antioxidant role at the specific concentrations, potentially mitigating ferroptosis in cells.
Likelihood of Preterm Birth in Patients After Antenatal Corticosteroid Administration in Relation to Diagnosis and Confounding Risk Factors: A Retrospective Cohort Study
Authors: Pauluschke-Fröhlich Jan , Berger Richard , Abele Harald , Plappert Claudia F. , Graf Joachim
Published: January 2025

Background: In the case of threatened preterm birth (PTB) before the 34th week of pregnancy, the application of antenatal corticosteroids (ACSs) for the maturation of the fetal lung is a standard procedure in perinatal medicine. Common diagnoses for ACS use in pregnancy are the preterm rupture of membranes (PPROMs), placental bleeding, premature labor, preeclampsia, oligohydramnios, amniotic infection syndrome (AIS), and cervical insufficiency. The aim of this study was to investigate whether the current diagnosis, which results in ACS, and the patient’s risk factors influence the risk of PTB events. Methods: The data of all affected women were extracted, who were hospitalized in 2016 due to a threatening PTB and administered corticosteroids in the German federal state Rhineland-Palatinate (n = 1544), so the study was conducted as a retrospective cohort trial. Frequency analyses, Friedman tests, Chi square tests, logistic regressions, Spearman correlation, and moderation analysis were performed to determine the Odds ratio (OR) for PTB in ACS patients in relation to diagnosis and risk factors. Results: Only 60% of all patients with PTB risk delivered prematurely, whereby patients with different diagnoses differ in terms of the PTB risk; the highest risk could be found in AIS (OR = 16.12) or preeclampsia (OR = 5.46). For prior PTB, stillbirth, or abortion, there is a moderation effect (based on the confounders), while multiple pregnancies influence the PTB risk irrespective of diagnosis (OR = 6.45). In the whole collective, the OR for PTB was 6.6 in relation to all pregnant women in Germany. Conclusions: A higher risk of PTB could be found in patients with a diagnosis of AIS, preeclampsia, as well as in multiple pregnancies. Prior PTB, stillbirth, or abortion act as a relevant confounder.
Digital Financial Inclusion and Economic Growth: The Moderating Role of Institutions in SADC Countries
Authors: Meniago Christelle
Published: January 2025

The purpose of this research is to examine the relationship between digital financial inclusion and economic growth in the SADC countries, while exploring the crucial moderating role of institutions. The digital financial inclusion (DFI) and institutional quality indices were constructed via Principal Component Analysis (PCA) to overcome the issue of multicollinearity. Using annual data from 2010 to 2023 and employing the system GMM technique, the findings of this study have persuasively supported the existence of a positive relationship between digital financial inclusion and economic growth in SADC countries, which signals that DFI is vital for boosting economic growth. The interaction term between the DFI index and institutional quality index also suggests a positive relationship, highlighting the need for the establishment of robust institutions and sound macroeconomic policies to ensure growth in the regional bloc. On the policy front, the findings indicate that efforts to expand digital financial inclusion in SADC countries should be complemented by institutional reforms aimed at improving governance, regulatory frameworks, rule of law, and legal protections. More specifically, this study suggests that SADC countries should focus on strengthening governance and regulatory frameworks to ensure transparency, security, and effective management of digital financial services. Improving legal protections, particularly around data security and consumer rights, is crucial to building trust in digital finance. Policymakers should also prioritize expanding digital infrastructure, especially in underserved areas, and addressing issues like limited technology access and digital literacy. Furthermore, fostering innovation in the fintech sector and implementing inclusive policies targeting marginalized groups will help drive wider adoption of digital financial services. By combining these reforms with institutional strengthening, SADC countries can create a conducive environment for sustainable economic growth through enhanced digital financial inclusion.
Advances in Whole Genome Sequencing: Methods, Tools, and Applications in Population Genomics
Authors: Lu Ying , Li Mengfei , Gao Zhendong , Ma Hongming , Chong Yuqing , Hong Jieyun , Wu Jiao , Wu Dongwang , Xi Dongmei , Deng Weidong
Published: January 2025

With the rapid advancement of high-throughput sequencing technologies, whole genome sequencing (WGS) has emerged as a crucial tool for studying genetic variation and population structure. Utilizing population genomics tools to analyze resequencing data allows for the effective integration of selection signals with population history, precise estimation of effective population size, historical population trends, and structural insights, along with the identification of specific genetic loci and variations. This paper reviews current whole genome sequencing technologies, detailing primary research methods, relevant software, and their advantages and limitations within population genomics. The goal is to examine the application and progress of resequencing technologies in this field and to consider future developments, including deep learning models and machine learning algorithms, which promise to enhance analytical methodologies and drive further advancements in population genomics.
The Unexplored Role of Connexin Hemichannels in Promoting Facioscapulohumeral Muscular Dystrophy Progression
Authors: Díaz-Ubilla Macarena , Retamal Mauricio A.
Published: January 2025

DUX4 is typically a repressed transcription factor, but its aberrant activation in Facioscapulohumeral Muscular Dystrophy (FSHD) leads to cell death by disrupting muscle homeostasis. This disruption affects crucial processes such as myogenesis, sarcolemma integrity, gene regulation, oxidative stress, immune response, and many other biological pathways. Notably, these disrupted processes have been associated, in other pathological contexts, with the presence of connexin (Cx) hemichannels—transmembrane structures that mediate communication between the intracellular and extracellular environments. Thus, hemichannels have been implicated in skeletal muscle atrophy, as observed in human biopsies and animal models of Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, and Dysferlinopathies, suggesting a potentially shared mechanism of muscle atrophy that has not yet been explored in FSHD. Despite various therapeutic strategies proposed to manage FSHD, no treatment or cure is currently available. This review summarizes the current understanding of the mechanisms underlying FSHD progression, with a focus on hormones, inflammation, reactive oxygen species (ROS), and mitochondrial function. Additionally, it explores the potential of targeting hemichannels as a therapeutic strategy to slow disease progression by preventing the spread of pathogenic factors between muscle cells.
Anticancer Plant Secondary Metabolites Evicting Linker Histone H1.2 from Chromatin Activate Type I Interferon Signaling
Authors: Vlasova Olga , Antonova Irina , Magomedova Khamis , Osipova Alena , Shtompel Polina , Borunova Anna , Zabotina Tatiana , Belitsky Gennady , Budunova Irina , Jordan Albert , Kirsanov Kirill , Yakubovskaya Marianna
Published: January 2025

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon (IFN) response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry, immunofluorescence staining and quantitative RT-PCR, we studied effects of PSMs both evicting linker histones from chromatin and not influencing their location in nucleus. We found that (1) 8 PSMs, evicting linker histone H1.2 from chromatin, activated significantly the type I IFN signaling pathway and out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression. Fisetin and quercetin, which also induced linker histone H1.2 eviction from chromatin, significantly activated only type I IFN signaling, but not LINE1 expression; (2) curcumin, sanguinarine and kaempferol, causing significant depletion of the chromatin-bound linker histone H1.4 but not significantly influencing H1.2 presence in chromatin, activate type I IFN signaling less intensively without any changes in LINE1 expression; (3) four PSMs, which did not cause linker histone eviction, displayed neither IFN signaling activation nor enhancement of LINE1 expression. Thus, we have shown for the first time that chromatin destabilization observed by depletion of chromatin-bound linker histone H1.2 caused by anticancer DNA-binding PSMs is accompanied by enhancement of type I IFN signaling, and that LINE1 expression often impacts this activation.
The Effect of Ionising Radiation on the Properties of Tumour-Derived Exosomes and Their Ability to Modify the Biology of Non-Irradiated Breast Cancer Cells—An In Vitro Study
Authors: Lach Michał Stefan , Wróblewska Joanna Patrycja , Michalak Marcin , Budny Bartłomiej , Wrotkowska Elżbieta , Suchorska Wiktoria Maria
Published: January 2025

The vast majority of breast cancer patients require radiotherapy but some of them will develop local recurrences and potentially metastases in the future. Recent data show that exosomal cargo is essential in these processes. Thus, we investigated the influence of ionising radiation on exosome properties and their ability to modify the sensitivity and biology of non-irradiated cells. Exosomes were isolated from breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) irradiated with 2 Gy (Exo 2 Gy) or no irradiation (Exo 0 Gy). Despite some differences in their molecular profiles, they did not affect cell viability, proliferation, cell cycle phase distribution, and radioresistance; however, both populations showed the ability to modify cell migration and invasion potential, as confirmed by the downregulation of β-catenin, which is responsible for maintaining the epithelial phenotype. Interestingly, exosomes from irradiated BCa cells were more actively deposited in the endothelial cells (EA.hy926). Furthermore, exosomes tend to lower the expression of CD31, which is responsible for maintaining intact vascularity. This preliminary study demonstrates the vital role of exosomes and their altered profile due to irradiation in the pathobiology of breast cancer.
The Role of Fractalkine in Diabetic Retinopathy: Pathophysiology and Clinical Implications
Authors: Lee Cheng-Yung , Yang Chang-Hao
Published: January 2025

Diabetic retinopathy (DR) is a complication of diabetes, characterized by progressive microvascular dysfunction that can result in vision loss. Chronic hyperglycemia drives oxidative stress, endothelial dysfunction, and inflammation, leading to retinal damage and complications such as neovascularization. Current treatments, including anti-VEGF agents, have limitations, necessitating the exploration of alternative therapeutic strategies. Fractalkine (CX3CL1), a chemokine with dual roles as a membrane-bound adhesion molecule and a soluble chemoattractant, has emerged as a potential therapeutic target. Its receptor, CX3CR1, is expressed on immune cells and mediates processes such as immune cell recruitment and microglial activation through intracellular signaling pathways. In DR, soluble fractalkine plays critical roles in retinal inflammation, angiogenesis, and neuroprotection, balancing tissue damage and repair. In DR, elevated fractalkine levels are associated with retinal inflammation and endothelial dysfunction. Experimental studies suggest that fractalkine deficiency exacerbates the severity of diabetic retinopathy (DR), whereas exogenous fractalkine appears to reduce inflammation, oxidative stress, and neuronal damage. However, its role in pathological angiogenesis within DR remains unclear and warrants further investigation. Preclinical evidence indicates that fractalkine may hold therapeutic potential, particularly in mitigating tissue injury and inflammation associated with early-stage DR.
Expanding the Potential of Circular RNA (CircRNA) Vaccines: A Promising Therapeutic Approach
Authors: Bu Tian , Yang Ziyu , Zhao Jian , Gao Yanmei , Li Faxiang , Yang Rong
Published: January 2025

In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, as an RNA vaccine, offers significant advantages in preventing infectious diseases by serving as a vector for protein expression through non-canonical translation. Notably, circRNA vaccines have demonstrated enduring antigenic expression and generate a larger percentage of neutralizing antibodies compared to mRNA vaccines administered at the same dosage. Furthermore, circRNA vaccines can elicit robust cellular and humoral immunity, indicating their potential for tumor vaccine development. However, certain challenges must be addressed to facilitate the widespread use of circRNA vaccines in both infectious disease prevention and tumor treatment. These challenges include the low efficiency of linear RNA circularization, the suboptimal targeting of delivery systems, and the assessment of potential side effects. This work aims to describe the characteristics and functions of circRNAs, elucidate the mechanism behind circRNA vaccines, and discuss their applications in the prevention of infectious diseases and the treatment of tumors, along with their potential future applications.
Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms
Authors: Anchimowicz Julia , Zielonka Piotr , Jakiela Slawomir
Published: January 2025

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides a comprehensive analysis of the effects of PSMs on mitochondrial health, with particular emphasis on their therapeutic potential. Emerging evidence shows that these metabolites improve mitochondrial function by reducing oxidative stress, promoting mitochondrial biogenesis, and regulating key processes such as apoptosis and mitophagy. Mitochondrial dysfunction, a hallmark of many pathologies, including neurodegenerative disorders, cardiovascular diseases, and metabolic syndrome, has been shown to benefit from the protective effects of PSMs. Recent studies show that PSMs can improve mitochondrial dynamics, stabilise mitochondrial membranes, and enhance bioenergetics, offering significant promise for the prevention and treatment of mitochondrial-related diseases. The molecular mechanisms underlying these effects, including modulation of key signalling pathways and direct interactions with mitochondrial proteins, are discussed. The integration of PSMs into therapeutic strategies is highlighted as a promising avenue for improving treatment efficacy while minimising the side effects commonly associated with synthetic drugs. This review also highlights the need for future research to elucidate the specific roles of individual PSMs and their synergistic interactions within complex plant matrices, which may further optimise their therapeutic utility. Overall, this work provides valuable insights into the complex role of PSMs in mitochondrial health and their potential as natural therapeutic agents targeting mitochondrial dysfunction.
Comparison of the Cytotoxic Mechanisms of Different Garlic (Allium sativum L.) Cultivars with the Crucial Involvement of Peroxisome Proliferator-Activated Receptor Gamma
Authors: Binduga Urszula E. , Kopeć Aneta , Skoczylas Joanna , Szychowski Konrad A.
Published: January 2025

Garlic (Allium sativum L.) is one of the oldest known useful plants, valued for thousands of years. This plant contains many biologically active compounds, including polyphenols, sterols, cysteine-sulfoxides, carbohydrates, proteins, and amino acids. The aim of our study was to compare the antioxidant potential, cytotoxicity, and apoptosis induction properties of four garlic cultivars—Harnaś, Ornak, Violeta, and Morado—in human squamous carcinoma (SCC-15) cells, colon adenocarcinoma (CACO-2) cells, and normal fibroblasts (BJ). Additionally, we investigated the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARγ), microtubule-associated protein 1 light chain 3 (LC3A), superoxide dismutase 1 (SOD1), and catalase (CAT) after treatment with the studied garlic extracts. Our study demonstrated that high ROS production was correlated with the strong toxicity of the garlic extracts. All studied extracts produced a lesser increase in ROS in normal BJ fibroblasts and were less toxic to these cells. The expression patterns of PPARγ, LC3A, SOD1, and CAT, along with chromatographic analysis, suggest differing mechanisms among the garlic cultivars. The highest levels of catechin, a known PPARγ agonist, were detected in the Harnaś (3.892 µg/mL) and Ornak (3.189 µg/mL) cultivars. A high catechin content was correlated with similar changes in PPARγ and related SOD1 and LC3A. Our findings showed the health-promoting and anticancer properties of garlic. However, we could not definitively identify which polyphenol or how it is involved in PPARγ activation. Further studies are required to elucidate the role of PPARγ in the mechanism of action of garlic extracts.
Phosphoenolpyruvate and Related Metabolic Pathways Contribute to the Regulation of Plant Growth and Development
Authors: Hu Runzhou , Yu Haiyang , Deng Jing , Chen Shanjing , Yang Ronglan , Xie Hongjun , Tang Xiao , Yu Yaying , Duan Yonghong , Zhang Meng , Zhu Mingdong , Yu Yinghong
Published: January 2025

Phosphoenolpyruvate (PEP) plays a key role in the development of plants and exists in a wide variety of species. Research on the metabolic activities of PEP in plants has received increasing attention. PEP regulates multiple processes in plant growth and development. This article provides a comprehensive summary of these pathways, including embryo formation, root development, synthesis of secondary metabolites, and the formation of lignification. We also summarize new findings, including PEP’s role in nodule energy sensing and carbon allocation under the influence of ozone. This review displays the complex and differential regulatory pathways in plant growth and development and provides a reference for basic and applied research on PEP metabolism in plants.
The Influence of Body Composition, Lifestyle, and Dietary Components on Adiponectin and Resistin Levels and AR Index in Obese Individuals
Authors: Polak-Szczybyło Ewelina , Tabarkiewicz Jacek
Published: January 2025

Adipose tissue of obese people secretes a number of adipokines, including adiponectin and resistin, which have an antagonistic effect on the human metabolism, influencing the pathogenesis of many diseases based on low-grade inflammation. Body composition analysis using bioelectrical impedance analysis (BIA) was performed in 84 adults with obesity, i.e., body mass index (BMI) greater than or equal to 30 kg/m2. Serum was collected to analyze the concentration of adiponectin (ApN) and resistin. The subjects additionally completed a food frequency questionnaire FFQ-6 and a three-day food diary. Adiponectin-resistin index (AR index) was calculated. The results show a positive correlation between resistin levels and BMI and subcutaneous fat content. AR index value was also positively associated with the amount of adipose tissue and body mass. Adiponectin level in the serum of the studied individuals decreased with the content of lean tissue. Adiponectin level also decreased with the amount of carbohydrates, amount of starch, and glycemic load of the diet. Resistin decreased in patients who frequently consumed white pasta and red meat, while AR index was positively associated with the amount of white rice and saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) consumed but negatively associated with the frequent consumption of carbohydrates, including starch. Physical activity was negatively correlated with adiponectin levels and AR index. We concluded that body composition significantly influenced serum resistin and adiponectin concentrations the AR index. Dietary components also had a significant effect.
Comparative Analysis of Complete Chloroplast Genomes and Phylogenetic Relationships in Medicinally Important Pantropical Genus Bauhinia s.s. (Leguminosae) from Southern Africa and Eastern Asia
Authors: Lin Yanxiang , Chen Yuan , Zhao Yanlin , Wu Wei , Yang Chengzi , Zheng Yanfang , Huang Mingqing
Published: January 2025

Bauhinia s.s. belongs to the Cercidoideae subfamily, located at the base of the Leguminosae family. It displays a variety of growth habits and morphologies, and is widely utilized as both ornamental and medicinal plants globally. The objective of this research is to uncover chloroplast genomes of species from Eastern Asia and Southern Africa, thereby advancing our understanding of the diversity within this genus. This study sequenced Bauhinia purpurea, Bauhinia brachycarpa var. microphylla, Bauhinia variegata var. candida, Bauhinia galpinii, and Bauhinia monandra using the Illumina platform and conducted the construction of phylogenetic trees as well as the estimation of divergence times. Compared to Asian species, the IR regions of African species underwent a contraction of approximately 100–400 bp. The phylogenetic analysis indicated that Asian and African species clustered into two distinct clades, with high support. The divergence of Bauhinia s.s. species occurred in the late Paleocene, and the rps18 and cemA genes were under positive selection. Six hypervariable regions were screened for evolutionary studies and the super-barcode data were used for species delimitation. The results revealed certain differences between African and Asian species in their chloroplast genomes of Bauhinia species.
Transcriptomic and Proteomic Analysis of Monkeypox Virus A5L-Expressing HEK293T Cells
Authors: Li Mingzhi , Xiong Jiaqi , Zhou Hao , Liu Jing , Wang Chenyi , Jia Mengle , Wang Yihao , Zhang Nannan , Chen Yanying , Zhong Tao , Zhang Zhicheng , Li Ruiying , Zhang Yuxin , Guo Yunli , Peng Qi , Kong Lingbao
Published: January 2025

Monkeypox (MPOX) is a zoonotic viral disease caused by the Monkeypox virus (MPXV), which has become the most significant public health threat within the Orthopoxvirus genus since the eradication of the Variola virus (VARV). Despite the extensive attention MPXV has garnered, little is known about its clinical manifestations in humans. In this study, a high-throughput RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was employed to investigate the transcriptional and metabolic responses of HEK293T cells to the MPXV A5L protein. RNA-seq analysis identified a total of 1473 differentially expressed genes (DEGs), comprising 911 upregulated and 562 downregulated genes. Additionally, LC-MS/MS analysis revealed 185 cellular proteins with significantly altered abundance ratios that interact with the A5L protein. Here, we perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the transcriptome and proteome signatures of MPXV A5L-expressing HEK293T cells to gain insights into the virus proteins-host interplay. Transcriptomic analysis revealed that transfection of the MPXV A5L protein modulated genes primarily associated with the cell cycle, ribosome, and DNA replication. Proteomic analysis indicated that this protein predominantly interacted with host ribosomal proteins and cytoskeletal proteins. The combination of transcriptomic and proteomic analysis offers new perspectives for understanding the interaction between pathogens and hosts. Our research emphasizes the significant role of MPXV A5L in facilitating viral internalization and assembly, as well as its impact on the host’s translation system.
Cellular Partners of Tobamoviral Movement Proteins
Authors: Ershova Natalia M. , Kamarova Kamila A. , Sheshukova Ekaterina V. , Komarova Tatiana V.
Published: January 2025

The size of viral genomes is limited, thus the majority of encoded proteins possess multiple functions. The main function of tobamoviral movement protein (MP) is to perform plasmodesmata gating and mediate intercellular transport of the viral RNA. MP is a remarkable example of a protein that, in addition to the initially discovered and most obvious function, carries out numerous activities that are important both for the manifestation of its key function and for successful and productive infection in general. Briefly, MP binds the viral genome, delivers it to the plasmodesmata (PD) and mediates its intercellular transfer. To implement the transport function, MP interacts with diverse cellular factors. Each of these cellular proteins has its own function, which could be different under normal conditions and upon viral infection. Here, we summarize the data available at present on the plethora of cellular factors that were identified as tobamoviral MP partners and analyze the role of these interactions in infection development.
Roles of the Receptor for Advanced Glycation End Products and Its Ligands in the Pathogenesis of Alzheimer’s Disease
Authors: Li Wen , Chen Qiuping , Peng Chengjie , Yang Dan , Liu Si , Lv Yanwen , Jiang Langqi , Xu Shijun , Huang Lihua
Published: January 2025

The Receptor for Advanced Glycation End Products (RAGE), part of the immunoglobulin superfamily, plays a significant role in various essential functions under both normal and pathological conditions, especially in the progression of Alzheimer’s disease (AD). RAGE engages with several damage-associated molecular patterns (DAMPs), including advanced glycation end products (AGEs), beta-amyloid peptide (Aβ), high mobility group box 1 (HMGB1), and S100 calcium-binding proteins. This interaction impairs the brain’s ability to clear Aβ, resulting in increased Aβ accumulation, neuronal injury, and mitochondrial dysfunction. This further promotes inflammatory responses and oxidative stress, ultimately leading to a range of age-related diseases. Given RAGE’s significant role in AD, inhibitors that target RAGE and its ligands hold promise as new strategies for treating AD, offering new possibilities for alleviating and treating this serious neurodegenerative disease. This article reviews the various pathogenic mechanisms of AD and summarizes the literature on the interaction between RAGE and its ligands in various AD-related pathological processes, with a particular focus on the evidence and mechanisms by which RAGE interactions with AGEs, HMGB1, Aβ, and S100 proteins induce cognitive impairment in AD. Furthermore, the article discusses the principles of action of RAGE inhibitors and inhibitors targeting RAGE-ligand interactions, along with relevant clinical trials.
Cooperative and Independent Functionality of tmRNA and SmpB in Aeromonas veronii: A Multifunctional Exploration Beyond Ribosome Rescue
Authors: Bai Taipeng , Li Juanjuan , Chi Xue , Li Hong , Tang Yanqiong , Liu Zhu , Ma Xiang
Published: January 2025

The trans-translation system, mediated by transfer-messenger RNA (tmRNA, encoded by the ssrA gene) and its partner protein SmpB, helps to release ribosomes stalled on defective mRNA and targets incomplete protein products for hydrolysis. Knocking out the ssrA and smpB genes in various pathogens leads to different phenotypic changes, indicating that they have both cooperative and independent functionalities. This study aimed to clarify the functional relationships between tmRNA and SmpB in Aeromonas veronii, a pathogen that poses threats in aquaculture and human health. We characterized the expression dynamics of the ssrA and smpB genes at different growth stages of the pathogen, assessed the responses of deletion strains ΔssrA and ΔsmpB to various environmental stressors and carbon source supplementations, and identified the gene-regulatory networks involving both genes by integrating transcriptomic and phenotypic analyses. Our results showed that the gene ssrA maintained stable expression throughout the bacterial growth period, while smpB exhibited upregulated expression in response to nutrient deficiencies. Compared to the wild type, both the ΔssrA and ΔsmpB strains exhibited attenuated resistance to most stress conditions. However, ΔssrA independently responded to starvation, while ΔsmpB specifically showed reduced resistance to lower concentrations of Fe3+ and higher concentrations of Na+ ions, as well as increased utilization of the carbon source β-Methyl-D-glucoside. The transcriptomic analysis supported these phenotypic results, demonstrating that tmRNA and SmpB cooperate under nutrient-deficient conditions but operate independently in nutrient-rich environments. Phenotypic experiments confirmed that SsrA and SmpB collaboratively regulate genes involved in siderophore synthesis and iron uptake systems in response to extracellular iron deficiency. The findings of the present study provide crucial insights into the functions of the trans-translation system and highlight new roles for tmRNA and SmpB beyond trans-translation.
Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells
Authors: De los Santos-Jiménez Juan , Campos-Sandoval José A. , Rosales Tracy , Ko Bookyung , Alonso Francisco J. , Márquez Javier , DeBerardinis Ralph J. , Matés José M.
Published: January 2025

Glutaminase controls the first step in glutaminolysis, impacting bioenergetics, biosynthesis and oxidative stress. Two isoenzymes exist in humans, GLS and GLS2. GLS is considered prooncogenic and overexpressed in many tumours, while GLS2 may act as prooncogenic or as a tumour suppressor. Glioblastoma cells usually lack GLS2 while they express high GLS. We investigated how GLS2 expression modifies the metabolism of glioblastoma cells, looking for changes that may explain GLS2’s potential tumour suppressive role. We developed LN-229 glioblastoma cells stably expressing GLS2 and performed isotope tracing using U-13C-glutamine and metabolomic quantification to analyze metabolic changes. Treatment with GLS inhibitor CB-839 was also included to concomitantly inhibit endogenous GLS. GLS2 overexpression resulted in extensive metabolic changes, altering the TCA cycle by upregulating part of the cycle but blocking the synthesis of the 6-carbon intermediates from acetyl-CoA. Expression of GLS2 caused downregulation of PDH activity through phosphorylation of S293 of PDHA1. GLS2 also altered nucleotide levels and induced the accumulation of methylated metabolites and S-adenosyl methionine. These changes suggest that GLS2 may be a key regulator linking glutamine and glucose metabolism, also impacting nucleotides and epigenetics. Future research should ascertain the mechanisms involved and the generalizability of these findings in cancer or physiological conditions.
Goose Deoxycholic Acid Ameliorates Liver Injury in Laying Hens with Fatty Liver Hemorrhage Syndrome by Inhibiting the Inflammatory Response
Authors: Wang Nannan , Li Weiwei , Ouyang Guangyi , Li Hengqi , Yang Jiancheng , Wu Gaofeng
Published: January 2025

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional and metabolic disease involving liver enlargement, hepatic steatosis, and hepatic hemorrhage as the primary symptoms. The syndrome is prone to occur during the peak laying period of laying hens, which has resulted in significant economic losses in the laying hen breeding industry; however, the specific pathogenesis of FLHS remains unclear. Our group and previous studies have shown that bile acid levels are significantly decreased during the development of fatty liver and that targeted activation of bile acid–related signaling pathways is beneficial for preventing and treating fatty liver. In this study, we generated a FLHS laying hen model by feeding hens a high-energy, low-protein diet, with goose deoxycholic acid (CDCA) given as an intervention. HE staining, fluorescence quantitative PCR, and ELISA were used to evaluate the effects of CDCA on pathological changes and inflammatory responses in the liver. The results showed that hepatic hemorrhage in FLHS laying hens was reduced after CDCA treatment. Furthermore, fat vacuoles and transaminase levels decreased significantly. In addition, expression levels of M1-type macrophage markers and polarization products were significantly reduced, and the expression of pro-inflammatory regulatory factors related to the JAK-STAT signaling pathway, LPS-TLR4-Myd88–NF-kB signaling pathway, and NLRP3 inflammasomes decreased significantly as well. Expression levels of M2-type macrophage markers and polarization products increased significantly, as did the expression of anti-inflammatory regulators related to the JAK-STAT signaling pathway. These results suggest that CDCA ameliorates liver injury in laying hens with FLHS by inhibiting macrophage M1-type polarization and the resulting pro-inflammatory response, thereby promoting M2-type macrophage polarization and an anti-inflammatory response.
Acute Effects of Wild Ginseng Extract on Exercise Performance, Cognitive Function, and Fatigue Recovery: A Randomized Cross-Over, Placebo-Controlled, and Double-Blind Study
Authors: Lee Sukho , Jung Hyun Chul , Sargent Michael , Kang Minsoo
Published: January 2025

This study aimed to investigate the acute effects of wild ginseng extract (Panax ginseng C.A. Meyer) on exercise performance, cognitive function, and fatigue recovery. Methods: Twelve healthy male participants were randomly assigned to receive either wild ginseng extract (WG) or a placebo prior to exercise trials, utilizing a double-blind, placebo-controlled cross-over design. The exercise protocol included 30 min cycling exercises followed by a 10-mile time trial, during which muscular power, strength, endurance, cognitive function, and fatigue were assessed. Additionally, biomarkers such as glucose, interleukin-6 (IL-6), myoglobin, total antioxidant capacity (TAC), and cortisol were measured. Repeated measures ANOVAs were used to analyze the effects of acute WG intake on the dependent variables. Results: In the placebo condition, both peak and mean power levels significantly decreased over time (p = 0.039 and p = 0.028, respectively), whereas no such decline was observed in the WG condition (p > 0.05). Furthermore, average reaction time (ART) was significantly delayed over time in the placebo trial (p = 0.005), while ART remained stable in the WG trial (p = 0.051). A significant increase in TAC was observed across time in the WG trial (p = 0.036), but no change was found in the placebo trial (p = 0.326). Cortisol levels significantly decreased over time in the WG trial (p = 0.001), while no change was observed in the placebo trial (p = 0.141). No significant differences were found for other variables between the WG and placebo trials (p > 0.05). Conclusions: The acute supplementation with WG positively influenced exercise performance by maintaining muscular power, reducing reaction time delay, and enhancing antioxidant capacity and cortisol regulation. These findings suggest that WG may be a promising ergogenic aid for improving exercise performance and recovery. NCT06679725 (ClinicalTrials.gov).
Turning the Tables: Loss of Adaptive Immunity Reverses Sex Differences in Tuberculosis
Authors: Hertz David , Eggers Lars , von Borstel Linda , Goldmann Torsten , Lotter Hanna , Schneider Bianca E.
Published: January 2025

Sex-based differences in innate immunity may play a crucial role in susceptibility to and progression of tuberculosis (TB), a disease that disproportionately affects men. This study aimed to examine whether early host–pathogen interactions contribute to the heightened vulnerability of males to Mycobacterium tuberculosis (Mtb) infection. Using recombination activating gene 2 knockout (RAG2 KO) mice, which lack adaptive immunity, we were able to isolate and analyze innate immune responses to Mtb without the influence of T and B cells. Surprisingly, and in stark contrast to wild-type mice that reflect the male bias as observed in humans, female RAG2 KO mice were more susceptible to Mtb than their male counterparts. Increased lung CFU in females was accompanied by a significant rise in inflammation, indicated by elevated levels of inflammatory cytokines and chemokines, as well as a massive influx of neutrophils into the lungs. In contrast, male mice exhibited higher levels of IFN-γ and CCL5, along with a greater presence of NK cells in their lungs, suggesting that, in the absence of adaptive immunity, males benefit from a more robust NK cell response, potentially offering greater protection by better controlling inflammation and slowing disease progression.
Supervised Machine Learning for Real-Time Intrusion Attack Detection in Connected and Autonomous Vehicles: A Security Paradigm Shift
Authors: Aloqaily Ahmad , Abdallah Emad E. , AbuZaid Hiba , Abdallah Alaa E. , Al-hassan Malak
Published: January 2025

Recent improvements in self-driving and connected cars promise to enhance traffic safety by reducing risks and accidents. However, security concerns limit their acceptance. These vehicles, interconnected with infrastructure and other cars, are vulnerable to cyberattacks, which could lead to severe costs, including physical injury or death. In this article, we propose a framework for an intrusion detection system to protect internal vehicle communications from potential attacks and ensure secure sent/transferred data. In the proposed system, real auto-network datasets with Spoofing, DoS, and Fuzzy attacks are used. To accurately distinguish between benign and malicious messages, this study employed seven distinct supervised machine-learning algorithms for data classification. The selected algorithms encompassed Decision Trees, Random Forests, Naive Bayes, Logistic Regression, XG Boost, LightGBM, and Multi-layer Perceptrons. The proposed detection system performed well on large real-car hacking datasets. We achieved high accuracy in identifying diverse electronic intrusions across the complex internal networks of connected and autonomous vehicles. Random Forest and LightGBM outperformed the other algorithms examined. Random Forest outperformed the other algorithms in the merged dataset trial, with 99.9% accuracy and the lowest computing cost. The LightGBM algorithm, on the other hand, performed admirably in the domain of binary classification, obtaining the same remarkable 99.9% accuracy with no computing overhead.
Clinical and Functional Outcomes of Peri-Implant Fractures Associated with Short Proximal Femur Nails: Prevention Strategies and Key Insights
Authors: Aguado-Maestro Ignacio , Valle-López Sergio , Simón-Pérez Clarisa , Frutos-Reoyo Emilio-Javier , García-Cepeda Ignacio , de Blas-Sanz Inés , Sanz-Peñas Ana-Elena , Diez-Rodríguez Jesús , Mencía-González Juan-Pedro , Sanz-Posadas Carlos
Published: January 2025

Background: Hip fractures are prevalent among the elderly and impose a significant burden on healthcare systems due to the associated high morbidity and costs. The increasing use of intramedullary nails for hip fracture fixation has inadvertently introduced risks; these implants can alter bone elasticity and create stress concentrations, leading to peri-implant fractures. The aim of this study is to investigate the outcomes of peri-implant hip fractures, evaluate the potential causes of such fractures, determine the type of treatment provided, assess the outcomes of said treatments, and establish possible improvement strategies. Methods: We conducted a retrospective observational study on 33 patients with peri-implant hip fractures (PIFs) who underwent surgical management at Río Hortega University Hospital from 2010 to 2022. The collected data included demographics, initial fracture characteristics, the peri-implant fracture classification, implant details, surgical outcomes, functional scores, and complications. Functional capacity was evaluated using the Parker Mobility Score (PMS). Results: The cohort (91% female, mean age 87.6 years) included 34 peri-implant fractures. The mean time from the initial fracture to the PIF was 47.2 months (nine patients developed PIFs within 2 months). Most fractures (76%) were managed with implant removal and the insertion of a long intramedullary nail, with cement augmentation in 31% of cases. The mean surgical time was 102 min, and the average hospital stay was 9.6 days. Postoperative complications occurred in 27%, with a perioperative mortality rate of 9%. Functional capacity showed a significant decline, with an average PMS loss of 4.16 points. Mortality at one year post-PIF was 36%, rising to 83% at five years. Radiographic consolidation was observed in 72% of cases at an average of 6.04 months, though 24% of patients died before consolidation. Statistically significant correlations were found for PMS pre-index fracture (PMS1: r = 0.354, p < 0.05), pre-PIF (PMS2: r = 0.647, p < 0.001), and post-PIF (PMS3: r = 0.604, p < 0.001). Conclusions: Peri-implant hip fractures present complex challenges due to their surgical difficulty and impact on patient mobility and survival. Successful management requires individualized treatment based on fracture type, implant positioning, and patient factors. These findings underscore the need for preventive measures, particularly in implant choice and techniques like overlapping and interlocking constructs, to minimize the secondary fracture risk.
Node Reporting and Data System 1.0 (Node-RADS) for the Assessment of Oncological Patients’ Lymph Nodes in Clinical Imaging
Authors: Parillo Marco , Quattrocchi Carlo Cosimo
Published: January 2025

The assessment of lymph node (LN) involvement with clinical imaging is a key factor in cancer staging. Node Reporting and Data System 1.0 (Node-RADS) was introduced in 2021 as a new system specifically tailored for classifying and reporting LNs on computed tomography (CT) and magnetic resonance imaging scans. The aim of this review is to compile the scientific evidence that has emerged since the introduction of Node-RADS, with a specific focus on its diagnostic performance and reliability. Node-RADS’s performance has been evaluated in various cancer types and anatomical sites, revealing a trend where higher Node-RADS scores correspond to a greater probability of metastatic LN with better diagnostic performances compared to using short axis diameter alone. Moreover, Node-RADS exhibits encouraging diagnostic value for both Node-RADS ≥ 3 and Node-RADS ≥ 4 cutoffs in predicting metastatic LN. In terms of Node-RADS scoring reliability, preliminary studies show promising but partially conflicting results, with agreement levels, mostly between two readers, ranging from fair to almost perfect. This review highlights a wide variation in methodologies across different studies. Thus, to fully realize the potential of Node-RADS in clinical practice, future studies should comprehensively evaluate its diagnostic accuracy, category-specific malignancy rates, and inter-observer agreement. Finally, although limited, promising evidence has suggested the following: a potential prognostic role for Node-RADS; the possible value of diffusion-weighted imaging for LNs classified as Node-RADS ≥ 3; a correlation between Node-RADS and certain texture features in CT; and improved diagnostic performance when Node-RADS is integrated into radiomics or clinical models.