bluuebunny/crossref_metadata_2025 huggingface dataset:
A Computational Recognition Analysis of Promising Prognostic Biomarkers in Breast, Colon and Lung Cancer Patients
Authors: Bakheet Tala , Al-Mutairi Nada , Doubi Mosaab , Al-Ahmadi Wijdan , Alhosaini Khaled , Al-Zoghaibi Fahad
Published: January 2025

Breast, colon, and lung carcinomas are classified as aggressive tumors with poor relapse-free survival (RFS), progression-free survival (PF), and poor hazard ratios (HRs) despite extensive therapy. Therefore, it is essential to identify a gene expression signature that correlates with RFS/PF and HR status in order to predict treatment efficiency. RNA-binding proteins (RBPs) play critical roles in RNA metabolism, including RNA transcription, maturation, and post-translational regulation. However, their involvement in cancer is not yet fully understood. In this study, we used computational bioinformatics to classify the functions and correlations of RBPs in solid cancers. We aimed to identify molecular biomarkers that could help predict disease prognosis and improve the therapeutic efficiency in treated patients. Intersection analysis summarized more than 1659 RBPs across three recently updated RNA databases. Bioinformatics analysis showed that 58 RBPs were common in breast, colon, and lung cancers, with HR values < 1 and >1 and a significant Q-value < 0.0001. RBP gene clusters were identified based on RFS/PF, HR, p-value, and fold induction. To define union RBPs, common genes were subjected to hierarchical clustering and were classified into two groups. Poor survival was associated with high genes expression, including CDKN2A, MEX3A, RPL39L, VARS, GSPT1, SNRPE, SSR1, and TIA1 in breast and colon cancer but not with lung cancer; and poor survival was associated with low genes expression, including PPARGC1B, EIF4E3, and SMAD9 in breast, colon, and lung cancer. This study highlights the significant contribution of PPARGC1B, EIF4E3, and SMAD9 out of 11 RBP genes as prognostic predictors in patients with breast, colon, and lung cancers and their potential application in personalized therapy.
Comprehensive Analysis of CaFAD Genes Involved in Fatty Acid Accumulation in Coffea arabica and Functional Characterization of CaFAD8 in Transgenic Arabidopsis thaliana
Authors: Zhang Zhenwei , Li Xuejun , Qi Meijun , Anwar Sumera , Wang Butian , Ge Yu
Published: January 2025

The quality of Coffee arabica L. beans, particularly the aroma, is a key determinant of commercial value. Fatty acids, as precursors of volatile aroma compounds, play a crucial role in this quality. Screening and identification of their related genes are of particular significance. This study identified 21 members of the CaFAD gene family in the C. arabica genome using bioinformatics tools. Gene duplication events observed in the CaFAD gene family were likely driven by natural selection and mutation pressure, with natural selection being more prominent. Transcriptome sequencing, qRT-PCR, and fatty acid profiling across four fruit developmental stages revealed that CaFAD8 was closely associated with fatty acid synthesis regulation. Fatty acid content was initially high but decreased during the later stages, while CaFAD8 expression showed an inverse pattern. Subcellular localization indicated that CaFAD8 functions primarily on the inner membrane. CaFAD8-OE heterologous expression experiment in Arabidopsis thaliana reduced the total fatty acid content in seeds but increased unsaturated fatty acids, including oleic, linoleic, and linolenic acids. These findings suggest that CaFAD8 promotes fatty acid unsaturation and provides insights into fatty acid metabolism in C. arabica. This study offers a foundation for understanding CaFAD gene regulation and supports breeding strategies for high-oil C. arabica varieties.
Activity of Azole and Non-Azole Substances Against Aspergillus fumigatus in Clinical and Environmental Samples to Address Antimicrobial Resistance
Authors: Sanseverino Isabella , Scaccabarozzi Diletta , Sanz Marcos Cuesta , Teixeira Miguel , Sabino Raquel , Prigitano Anna , Porcel-Rodríguez Elena , Marinov Dimitar , Gómez Livia , Lahm Armin , Romanò Luisa , Lettieri Teresa
Published: January 2025

Aspergillus fumigatus is a common fungus which has gained attention due to its resistance to azole compounds, substances used in both medical and agricultural settings. One of the genetic alterations responsible for this resistance is the mutation TR34/L98H in the cyp51A gene. The aim of this study was to understand the impact of azoles and non-azoles on Aspergillus fumigatus. By examining clinical samples, soil samples, and compost material, this research aims to provide insights into the susceptibility of these strains to antifungal substances. To deepen our understanding of the factors potentially involved in antifungal resistance, we combined in vitro studies of sixteen compounds against Aspergillus fumigatus with results from the sequencing of the cyp51 gene. We observed that compounds generally displayed a similar pattern activity against wild-type Aspergillus fumigatus. Non-azoles, except Pyrisoxazole and Amisulbrom, did not show any activity against Aspergillus fumigatus, while azole compounds displayed differential activity against the fungus, except for Tetraconazole. For the mutant strains, a generally similar activity was observed in both clinical and environmental samples, likely due to the same mutation in all the isolates. The implications of these findings may be relevant for better understanding the relationship between Aspergillus fumigatus and its ability to develop resistance to antifungal substances.
Growth-Inhibitory Effect of Chicken Egg Yolk Polyclonal Antibodies (IgY) on Zoonotic Pathogens Campylobacter jejuni, Salmonella spp. and Escherichia coli, In Vitro
Authors: Czoska Paulina , Tarsalewska Karolina , Ponichtera Magdalena , Rybicka Magda , Sowa-Rogozinska Natalia , Sominka-Pierzchlewicz Hanna , Stodolna Aleksandra , Ogonowska Patrycja , Kosciuk Aleksandra , Glosnicka Renata , Bielawski Krzysztof Piotr
Published: January 2025

The overuse of antibiotics in animal husbandry has driven the search for alternative strategies to combat zoonotic pathogens. Foodborne zoonotic diseases caused by pathogenic bacteria pose a significant threat to human health, and therefore food safety should be a priority. This study investigates the in vitro inhibitory effects of chicken egg yolk immunoglobulin Y (IgY) on the growth and viability of three major foodborne pathogens: Campylobacter jejuni, Salmonella spp., and Escherichia coli. IgY was isolated from immunized hen egg yolks using a modified water dilution method, and its antigen-specificity confirmed through agglutination assays. Growth inhibition was evaluated across multiple doses and time points, revealing a dose-dependent bacteriostatic effect against all tested pathogens. A single dose of IgY (0.5 mg/mL) significantly reduced C. jejuni counts by up to 7 log, while repeated doses were required for Salmonella spp. and E. coli. These findings highlight egg yolk immunoglobulin’s potential as a source of sustainable, effective, ethical, readily available, and inexpensive antibiotic substitutes in livestock management. Future research will focus on validating these results in vivo and exploring large-scale production of IgY for practical application in animal healthcare.
Correction: Franceschi et al. Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation. Int. J. Mol. Sci. 2022, 23, 5978
Authors: Franceschi Sara , Lessi Francesca , Morelli Mariangela , Menicagli Michele , Pasqualetti Francesco , Aretini Paolo , Mazzanti Chiara Maria
Published: January 2025

In the original publication [...]
Exploring the Post Mortem Interval (PMI) Estimation Model by circRNA circRnf169 in Mouse Liver Tissue
Authors: Fu Jiewen , Song Binghui , Qian Jie , Cheng Jingliang , Chiampanichayakul Sawitree , Anuchapreeda Songyot , Fu Junjiang
Published: January 2025

Estimating the post mortem interval (PMI) is a crucial and contentious issue in forensic research, particularly in criminal cases. Traditional methods for PMI estimation are limited by constraints and inaccuracies. Circular RNA (circRNA), formed through exon or intron looping to create a complete circular structure without a 5′ end cap and a 3′ poly(A) tail, exhibits exceptional stability, abundance, and tissue-specific characteristics that make it potentially valuable for PMI estimation. However, research on the exploration or application of circRNA in PMI estimation has been limited. This study aims to investigate the correlation between circRNA and PMI. In this study, liver tissue samples were collected from mice at six different time points at 4 °C, 18 °C, 25 °C, and 35 °C, respectively. The reference gene 28S rRNA and the biomarker circRnf169 were successfully screened. Quantitative PCR was employed to examine the correlation between circRnf169 levels and PMI. At 4 °C, the level of circRnf169 decreased with prolonged PMI, whereas at 18 °C, 25 °C, and 35 °C, the circRnf169 RNA was degraded rapidly, indicating that circRnf169 is suitable for PMI estimation at low temperatures or early PMI. These findings suggest the establishment of mathematical model for early PMI based on circRnf169 using liver tissue, which may serve as a reliable marker. Further research is required in order to develop more markers in mice and/or to validate these mathematical models in human samples.
Graphene Quantum Dots in Bacterial Cellulose Hydrogels for Visible Light-Activated Antibiofilm and Angiogenesis in Infection Management
Authors: Zmejkoski Danica Z. , Zdravković Nemanja M. , Mitić Dijana D. , Marković Zoran M. , Budimir Filimonović Milica D. , Milivojević Dušan D. , Todorović Marković Biljana M.
Published: January 2025

A novel bacterial cellulose (BC)-based composite hydrogel with graphene quantum dots (BC-GQDs) was developed for photodynamic therapy using blue and green light (BC-GQD_blue and BC-GQD_green) to target pathogenic bacterial biofilms. This approach aims to address complications in treating nosocomial infections and combating multi-drug-resistant organisms. Short-term illumination (30 min) of both BC-GQD samples led to singlet oxygen production and a reduction in pathogenic biofilms. Significant antibiofilm activity (>50% reduction) was achieved against Staphylococcus aureus and Escherichia coli with BC-GQD_green, and against Pseudomonas aeruginosa with BC-GQD_blue. Atomic force microscopy images revealed a substantial decrease in biofilm mass, accompanied by changes in surface roughness and area, further confirming the antibiofilm efficacy of BC-GQDs under blue and green light, without any observed chemical alterations. Additionally, the biocompatibility of BC-GQDs was demonstrated with human gingival fibroblasts (HGFs). For the first time, in vitro studies explored the visible light-induced potential of BC-GQD composites to promote wound healing processes, showing increased migratory potential and the upregulation of eNOS and MMP9 gene expressions in HGFs. Chemical characterization revealed a 70 nm upshift in the photoluminescence emission spectra compared to the excitation wavelength. These novel photoactive BC-GQD hydrogel composites show great promise as effective agents for wound healing regeneration and infection management.
A Simplified Method for the Isolation of Extracellular Vesicles from Probiotic Bacteria and Their Characterization
Authors: Sawant Harshal , Bihl Ji , Borthakur Alip
Published: January 2025

Probiotic bacteria are normal inhabitants of a healthy human gut, conferring multiple beneficial effects on the gut and beyond. Under various disease states, the abundance and diversity of beneficial bacteria are significantly decreased, a process called dysbiosis. Among the intra- and extracellular components of probiotics, the extracellular vesicles (EVs) secreted by them have recently garnered significant attention as potential mediators of probiotics’ effects on host health. Further, these nanosized particles that encapsulate a wide range of bioactive molecules (proteins, lipids, RNA, and DNA) are standing out as key factors that could mediate gut microbiota–host communication and confer ameliorating effects in experimental inflammatory, metabolic, and cardiovascular disease models. However, a standard protocol of EV isolation from probiotic bacteria, not varying from lab to lab, must be established to achieve consistency in the experimental results in these pre-clinical models. Our current study compared two commonly used methods for EV isolation from biological samples, ultracentrifugation and precipitation, to develop a standard protocol for isolating EVs from the probiotics Lactobacillus acidophilus (LA), a Gram-positive bacterium, and Escherichia coli Nissle (EcN), a Gram-negative bacterium. The ultracentrifugation method gave ~1.5-fold higher EV yield for both LA and EcN compared to the precipitation method. Further, EcN released a higher level of EVs compared to LA. EVs were quantified and characterized by nanoparticle-tracking analysis (NTA) and by measuring the specific surface biomarkers using Western blot. Here, we describe our standardized step-by-step protocol for isolating EVs from probiotic bacteria and their characterization.
The Cell States of Sea Urchin During Metamorphosis Revealed by Single-Cell RNA Sequencing
Authors: Ge Hui , Huang Yongyu , Zhang Lili , Huang Shiyu , Wang Guodong
Published: January 2025

Metamorphosis is a key process in the life history of sea urchin Heliocidaris crassispina. However, the understanding of its molecular mechanisms is still lacking, especially the basic cell biology pre-metamorphosis and post-metamorphosis. Therefore, we employed single-cell RNA sequencing to delineate the cellular states of larvae and juveniles of H. crassispina. Our investigation revealed that the cell composition in sea urchins comprises six primary populations, encompassing nerve cells, skeletogenic cells, immune cells, digestive cells, germ cells, and muscle cells. Subsequently, we identified subpopulations within these cells. Our findings indicated that the larval peripheral nerves were discarded during metamorphosis. A decrease in the number of spicules was observed during this process. Additionally, we examined the differences between larval and adult pigment cells. Meanwhile, cellulase is highlighted as an essential factor for the development of competent juveniles. In summary, this study not only serves as a valuable resource for future research on sea urchins but also deepens our understanding of the intricate metamorphosis process.
In Silico Born Designed Anti-EGFR Aptamer Gol1 Has Anti-Proliferative Potential for Patient Glioblastoma Cells
Authors: Golovin Andrey , Dzarieva Fatima , Rubetskaya Ksenia , Shamadykova Dzhirgala , Usachev Dmitry , Pavlova Galina , Kopylov Alexey
Published: January 2025

The epidermal growth factor receptor (EGFR) is one of the key oncomarkers in glioblastoma (GB) biomedical research. High levels of EGFR expression and mutations have been found in many GB patients, making the EGFR an attractive target for therapeutic treatment. The EGFRvIII mutant is the most studied, it is not found in normal cells and is positively associated with tumor cell aggressiveness and poor patient prognosis, not to mention there is a possibility of it being a tumor stem cell marker. Some anti-EGFR DNA aptamers have already been selected, including the aptamer U2. The goal of this study was to construct a more stable derivative of the aptamer U2, while not ruining its functional potential toward cell cultures from GB patients. A multiloop motif in a putative secondary structure of the aptamer U2 was taken as a key feature to design a novel minimal aptamer, Gol1, using molecular dynamics simulations for predicted 3D models. It turned out that the aptamer Gol1 has a similar putative secondary structure, with G-C base pairs providing its stability. The anti-proliferative activities of the aptamer Gol1 were assessed using patient-derived GB continuous cell cultures, G01 and BU881, with different abundances of EGFR and EGFRvIII. The transcriptome data for the cell culture G01, after aptamer Gol1 treatment, revealed significant changes in gene expression; it induced the transcription of genes associated with neurogenesis and cell differentiation, and it decreased the transcription of genes mediating key nuclear processes. There were significant changes in the gene transcription of key pro-oncogenic signaling pathways mediated by the EGFR. Therefore, the aptamer Gol1 could potentially be an efficient molecule for translation into biomedicine, in order to develop targeted therapy for GB patients.
Non-Immune Functions of Innate Immunity Acting on Physiological Processes: Insights from Drosophila
Authors: Li Xiaoyan , Wang Xiaomin , Shang Zhen , Yang Shan , Tang Yan , Xu Wenhua
Published: January 2025

As the first line of host immune defense, innate immunity plays a key role in warding off foreign pathogens and damage. Drosophila melanogaster, as a classical model animal for more than 100 years, is an important research model for studying innate immunity. In recent years, scientists have made remarkable progress in the recognition mechanisms of innate immunity, the mechanisms of effector molecules, and the modes of their response at the cellular and tissue levels. However, the interaction between innate immunity and other physiological functions remains relatively novel and has yet to be systematically explored. Here, we first briefly discuss the link between the innate immunity system and physiological regulation, from several representative perspectives such as sleep, insulin, and brain function. Then, using Drosophila as a model, we provide an overview of the physiological system and specifically summarize the research on the regulation of physiology by innate immunity, covering sleep, lipid metabolism, development, neurodegenerative diseases, memory, feeding, lifespan, movement, and antioxidation. This review provides valuable perspectives into how innate immunity influences other physiological processes, providing a deeper understanding of the complex roles underlying innate immunity.
Coumarin Promotes Hypocotyl Elongation by Increasing the Synthesis of Brassinosteroids in Plants
Authors: Liu Siqi , Ma Aolin , Li Jie , Du Zhixuan , Zhu Longfei , Feng Guanping
Published: January 2025

Coumarins are natural products commonly found in plants and are typical allelopathic substances that strongly affect the growth of plants after being exudated from the root and help plants absorb Fe in cases of iron deficiency. Although coumarins have been found to have multiple effects, this understanding is still relatively limited. Here, we show that coumarin significantly promotes the elongation of the hypocotyl by enhancing cell elongation. Further research has found that coumarin increases the content of BR in plants by enhancing the expression of brassinosteroid (BR) synthesis genes. The effect of coumarin on promoting hypocotyl elongation is completely blocked by the mutation of the BR synthesis gene DEETIOLATED 2 (DET2) or the co-addition of the BR synthesis inhibitor brassinazole (BRZ). Genetic analysis using Arabidopsis mutants showed that coumarin promoting hypocotyl elongation depends on the signaling pathway of the BRs. Overall, coumarin promotes elongation of the hypocotyl by increasing the synthesis of BRs in plants. These results provide us with new insights into the role of coumarins and offer strong theoretical support for the mechanisms of interactions between plants.
Potential Molecular Interactions and In Vitro Hyperthermia, Thermal, and Magnetic Studies of Bioactive Nickel-Doped Hydroxyapatite Thin Films
Authors: Asghar Muhammad Sohail , Ghazanfar Uzma , Rizwan Muhammad , Manan Muhammad Qasim , Baig Athar , Qaiser Muhammad Adnan , Haq Zeenat , Wang Lei , Duta Liviu
Published: January 2025

The treatment of bone cancer often necessitates the surgical removal of affected tissues, with artificial implants playing a critical role in replacing lost bone structure. Functionalized implants represent an innovative approach to improve bio-integration and the long-term effectiveness of surgery in treating cancer-damaged bones. In this study, nickel-substituted hydroxyapatite (Ni:HAp) nanoparticles were deposited as thin films using laser pulses in the range of 30,000–60,000. Comprehensive structural, infrared, optical, morphological, surface, and magnetic evaluations were conducted on the synthesized Ni:HAp thin films. The magnetic hysteresis (M-H) loop demonstrated an increase in the saturation magnetization of the films with a higher number of laser pulses. A minimum squareness ratio of 0.7 was observed at 45,000 laser pulses, and the M-H characteristics indicated a shift toward ferromagnetic behavior, achieving the desired thermal response through an alternating magnetic field application within 80 s. Thermogravimetric analysis revealed distinct thermal stability, with the material structure exhibiting 46% degradation at 800 °C. The incorporation of bioactive magnetic nanoparticles in the thin film holds significant promise for magnetic hyperthermia treatment. Using HDOCK simulations, the interactions between ligand molecules and proteins were also explored. Strong binding affinities with a docking score of −67.73 were thus observed. The presence of Ca2+ ions enhances electrostatic interactions, providing valuable insights into the biochemical roles of the ligand in therapeutic applications. Intravenous administration of magnetic nanoparticles, which subsequently aggregate within the tumor tissue, combined with an applied alternating magnetic field, enable targeted heating of the tumor to 45 °C. This focused heating approach selectively targets cancer cells while preserving the surrounding healthy tissue, thereby potentially enhancing the effectiveness of hyperthermia therapy in cancer treatment.
Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways
Authors: Tkaczenko Halina , Kurhaluk Natalia
Published: January 2025

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December 2024, highlighting the central role of the Nrf2 pathway. As a critical regulator of oxidative stress and metabolic adaptation, Nrf2 mediates the benefits of these interventions. This article presents an innovative approach to understanding the role of Nrf2 in the regulation of oxidative stress and inflammation, highlighting its potential in the prevention and treatment of various diseases, including cancer, neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, inflammatory conditions, ageing, and infections such as COVID-19. The novelty of this study is to investigate the synergistic effects of bioactive compounds found in functional foods (such as polyphenols, flavonoids, and vitamins) and exercise-induced oxidative stress on the activation of the Nrf2 pathway. This combined approach reveals their potential to improve insulin sensitivity and lipid metabolism and reduce inflammation, offering a promising strategy for the management of chronic diseases. However, there are significant gaps in current research, particularly regarding the molecular mechanisms underlying the interaction between diet, physical activity, and Nrf2 activation, as well as their long-term effects in different populations, including those with chronic diseases. In addition, the interactions between Nrf2 and other critical signalling pathways, including AMPK, NF-κB, and PI3K/Akt, and their collective contributions to metabolic health are explored. Furthermore, novel biomarkers are presented to assess the impact of these synergistic strategies, such as the NAD+/NADH ratio, the GSH ratio, and markers of mitochondrial health. The findings provide valuable insights into how the integration of an antioxidant-rich diet and regular exercise can improve metabolic health by activating Nrf2 and related molecular pathways and represent promising strategies for the prevention and treatment of metabolic disorders. Further studies are needed to fully understand the therapeutic potential of these interventions in diseases related to oxidative stress, such as cardiovascular disease, neurodegenerative disease, diabetes, and cancer.
From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease
Authors: Marzetti Emanuele , Di Lorenzo Rosa , Calvani Riccardo , Pesce Vito , Landi Francesco , Coelho-Júnior Hélio José , Picca Anna
Published: January 2025

The coordination of cytoskeletal proteins shapes cell architectures and functions. Age-related changes in cellular mechanical properties have been linked to decreased cellular and tissue dysfunction. Studies have also found a relationship between mitochondrial function and the cytoskeleton. Cytoskeleton inhibitors impact mitochondrial quality and function, including motility and morphology, membrane potential, and respiration. The regulatory properties of the cytoskeleton on mitochondrial functions are involved in the pathogenesis of several diseases. Disassembly of the axon’s cytoskeleton and the release of neurofilament fragments have been documented during neurodegeneration. However, these changes can also be related to mitochondrial impairments, spanning from reduced mitochondrial quality to altered bioenergetics. Herein, we discuss recent research highlighting some of the pathophysiological roles of cytoskeleton disassembly in aging, neurodegeneration, and neuromuscular diseases, with a focus on studies that explored the relationship between intermediate filaments and mitochondrial signaling as relevant contributors to cellular health and disease.
Chitosan Nanoparticle-Encapsulated Cordyceps militaris Grown on Germinated Rhynchosia nulubilis Reduces Type II Alveolar Epithelial Cell Apoptosis in PM2.5-Induced Lung Injury
Authors: Kim Hyo-Min , Kim Jong-Heon , Park Byung-Jin , Park Hye-Jin
Published: January 2025

Chitosan nanoparticles (CNPs) were synthesized in this study to enhance the limited bioactivity and stability of Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) and effectively deliver it to target tissues. Under optimized conditions, stable encapsulation of GRC was achieved by setting the chitosan (CHI)-to-tripolyphosphate (TPP) ratio to 4:1 and adjusting the pH of TPP to 2, resulting in a zeta potential of +22.77 mV, which indicated excellent stability. As the concentration of GRC increased, the encapsulation efficiency decreased, whereas the loading efficiency increased. Fourier-transform infrared (FT-IR) spectroscopy revealed shifts in the amide I and II bands of CHI from 1659 and 1578 to 1639 cm⁻1, indicating hydrogen bonding and successful encapsulation of GRC encapsulated with CNPs (GCN). X-ray diffraction (XRD) examination revealed the transition of the nanoparticles from a crystalline to an amorphous state, further confirming successful encapsulation. In vivo experiments demonstrated that GCN treatment significantly reduced lung injury scores in fine particulate matter (PM2.5)-exposed mice (p < 0.05) and alleviated lung epithelial barrier damage by restoring the decreased expression of occludin protein (p < 0.05). In addition, GCN decreased the PM2.5-induced upregulation of MMP-9 and COL1A1 mRNA expression levels, preventing extracellular matrix (ECM) degradation and collagen accumulation (p < 0.05). GCN exhibited antioxidant effects by reducing the mRNA expression of nitric oxide synthase (iNOS) and enhancing both the protein and mRNA expression of superoxide dismutase (SOD-1) caused by PM2.5, thereby alleviating oxidative stress (p < 0.05). In A549 cells, GCN significantly reduced PM2.5-induced reactive oxygen species (ROS) production compared with GRC (p < 0.05), with enhanced intracellular uptake confirmed using fluorescence microscopy (p < 0.05). In conclusion, GCN effectively alleviated PM2.5-induced lung damage by attenuating oxidative stress, suppressing apoptosis, and preserving the lung epithelial barrier integrity. These results emphasize its potential as a therapeutic candidate for preventing and treating the lung diseases associated with PM2.5 exposure.
Identification of Fungal Metabolite Gliotoxin as a Potent Inhibitor Against Bacterial O-Acetylserine Sulfhydrylase CysK and CysM
Authors: Rahman Azizur , Ono Katsuhiko , Toyomoto Touya , Hanaoka Kenjiro , Sawa Tomohiro
Published: January 2025

Cysteine is an essential amino acid for sustaining life, including protein synthesis, and serves as a precursor for antioxidant glutathione. Pathogenic bacteria synthesize cysteine via a two-step enzymatic process using serine as the starting material. The first step is catalyzed by serine acetyltransferase, also known as CysE, and the second by O-acetylserine sulfhydrylase (OASS), referred to as CysK or CysM. This cysteine biosynthetic pathway in bacteria differs significantly from that in mammals, making it an attractive target for the development of novel antibacterial agents. In this study, we aimed to identify OASS inhibitors. To achieve this, a high-throughput screening system was developed to analyze compounds capable of inhibiting CysK/CysM activity. Screening 168,640 compounds from a chemical library revealed that gliotoxin, a fungal metabolite, strongly inhibits both CysK and CysM. Furthermore, gliotoxin significantly suppressed the growth of Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, under cystine-deficient conditions. Gliotoxin possesses a unique disulfide structure classified as epipolythiodioxopiperazine. To date, no studies have reported OASS inhibition by compounds with this structural motif, highlighting its potential for future structural optimization. The screening system developed in this study is expected to accelerate the discovery of functional CysK/CysM inhibitors, providing a foundation for novel antibacterial strategies.
Altered Sertoli Cell Function Contributes to Spermatogenic Arrest in Dogs with Chronic Asymptomatic Orchitis
Authors: Rehder Pauline , Packeiser Eva-Maria , Körber Hanna , Goericke-Pesch Sandra
Published: January 2025

Acquired infertility due to chronic asymptomatic orchitis (CAO) is a common finding in male dogs. It is characterized by spermatogenic arrest, a significant reduction in spermatogonia, immune cell infiltration and a disruption of the blood–testis barrier. Sertoli cells are a key factor for spermatogenesis and the testicular micromilieu. We hypothesize altered Sertoli cell function to be involved in the pathogenesis of canine CAO. Consequently, the aim was to gain further insights into the spermatogonial stem cell niche and Sertoli cell function in CAO-affected dogs. Therefore, the testicular expression of the Sertoli cell-derived factors bFGF, GDNF, WNT5A, BMP4, CXCL12 and LDHC were evaluated in 15 CAO testis tissues and 10 normospermic controls by relative quantitative real-time PCR (qPCR). Additionally, the protein expression patterns of bFGF, GDNF and WNT5A were visualized immunohistochemically (IHC). This study revealed an overexpression of bFGF (IHC, p < 0.0001), GDNF (qPCR, p = 0.0036), WNT5A (IHC, p = 0.0066) and CXCL12 (qPCR, p = 0.0003) and a reduction in BMP4 (qPCR, p = 0.0041) and LDHC (qPCR, p = 0.0003) in CAO-affected testis in dogs, clearly confirming impaired Sertoli cell function in canine CAO. Sertoli cell function is essential for spermatogenesis and must be considered for potential therapeutic approaches.
Coronary CT Angiography in the Emergency Department: State of the Art and Future Perspectives
Authors: De Vita Antonio , Covino Marcello , Pontecorvo Sara , Buonamassa Giacomo , Marino Angelo Giuseppe , Marano Riccardo , Natale Luigi , Liuzzo Giovanna , Burzotta Francesco , Franceschi Francesco
Published: January 2025

About 5% of annual access to emergency departments (EDs) and up to 25–30% of hospital admissions involve patients with symptoms suggestive of acute coronary syndrome (ACS). The process of evaluating and treating these patients is highly challenging for clinicians because failing to correctly identify an ACS can result in fatal or life-threatening consequences. However, about 50–60% of these patients who are admitted to the hospital because of chest pain are found to have no ACS. Coronary computed tomographic angiography (CCTA) has emerged as a proposed new frontline test for managing acute chest pain in the ED, particularly for patients with low-to-intermediate risk. This narrative review explores the potential of adopting an early CCTA-based approach in the ED, its significance in the era of high-sensitivity troponins, its application to high-risk patients and its prognostic value concerning atherosclerotic burden and high-risk plaque features. Additionally, we address clinical and technical issues related to CCTA use for triaging acute chest pain in the ED, as well as the role of functional testing. Finally, we aim to provide insight into future perspectives for the clinical application of CCTA in the ED.
Mixed Reality (Holography)-Guided Minimally Invasive Cardiac Surgery—A Novel Comparative Feasibility Study
Authors: Aye Winn Maung Maung , Kiraly Laszlo , Kumar Senthil S. , Kasivishvanaath Ayyadarshan , Gao Yujia , Kofidis Theodoros
Published: January 2025

The operative field and exposure in minimally invasive cardiac surgery (MICS) are limited. Meticulous preoperative planning and intraoperative visualization are crucial. We present our initial experience with HoloLens® 2 as an intraoperative guide during MICS procedures: aortic valve replacement (AVR) via right anterior small thoracotomy, coronary artery bypass graft surgery (CABG) via left anterior small thoracotomy (LAST), and pulmonary valve replacement (PVR) via LAST. Three-dimensional (3D) segmentations were performed using the patient’s computer tomography (CT) data subsequently rendered into a 3D hologram on the HoloLens® 2. The holographic image was then superimposed on the patient lying on the operating table, using the xiphoid and the clavicle as landmarks, and was used as a real-time anatomical image guide for the surgery. The incision site marking made using HoloLens® 2 differed by one intercostal space from the marking made using a conventional surgeon’s mental reconstructed image from the patient’s preoperative imaging and was found to be a more appropriate site of entry into the chest for the structure of interest. The transparent visor of the HoloLens® 2 provided unobstructed views of the operating field. A mixed reality (MR) device could contribute to preoperative surgical planning and intraoperative real-time image guidance, which facilitates the understanding of anatomical relationships. MR has the potential to improve surgical precision, decrease risk, and enhance patient safety.
The Protective Role of Physical Fitness Level Against Obesity and Body Dissatisfaction in French-Canadian Youth
Authors: Leone Mario , Thibault Isabelle , Bui Hung Tien , Kalinova Emilia , Lemoyne Jean , Gagnon Dominic , Larivière Georges , Allisse Maxime
Published: January 2025

Background: The obesity epidemic among adolescents significantly impacts not only their physical health but also various psychological factors, including their perception of body image. Thus, this study pursued three main objectives: (1) to update the reference standard values for all the physical fitness tests performed; (2) to examine the impact of overweight and obesity on factors influencing physical fitness in adolescents; and (3) to determine the relationship between the physical fitness level and the body image dissatisfaction among a population of French-Canadian adolescents. Methods: A total of 1862 adolescents aged 12 to 17 (1008 boys and 854 girls) participated in this study. Data were collected from 12 French-language high-schools from different socioeconomic backgrounds and spread across four regions of the province of Québec, Canada. Anthropometric measures (body mass, body height, body mass index (BMI), waist circumference, waist-to-height ratio) and fitness tests (aerobic power, anaerobic power, muscle endurance, muscular power, flexibility) were conducted. To assess adolescents’ body perception, a silhouette scale was used. Results: Standardized normative values were established for each fitness test (Lambda Mu Sigma; LMS method). In boys, performance generally improved with age, except for the V-test and sit-ups, which remained stable, and VO2peak, which declined during adolescence in both genders (unpaired t-test and Cohen’s d effect size). In girls, only the vertical jump and 30 m sprint improved with age, while the other tests stabilized by age 13. Fitness level was significantly influenced by obesity status. Boys and girls with a normal BMI performed better than those who were overweight or obese (ANOVA = p < 0.001 and effect size F). Girls appeared to be less affected by obesity status, with differences between overweight and obese groups rarely being significant (p > 0.05). Fitness level was also linked to body satisfaction, with satisfied adolescents generally achieving better scores than dissatisfied ones, even among those with a typical BMI. Socioeconomic status did not impact body image perception in boys (p = 0.351). In contrast, girls from lower socioeconomic backgrounds exhibited significantly more negative perceptions (p = 0.002) than their peers from more affluent families. Conclusions: Obesity status is strongly associated with poorer performance on fitness tests. Conversely, higher levels of physical fitness are linked to improved body image satisfaction. This positive relationship between fitness and body image holds true even for individuals with a healthy body weight (typical BMI).
Auditors’ Life Cycle in Clients and Auditor Independence
Authors: Nwaeze Emeka T.
Published: January 2025

This study hypothesizes that, in client firms, audit teams or auditors go through life cycle phases—entry, adjustment, and recursion—that give rise to distinct patterns of independence across time. The life cycle paradigm depicts the auditors as facing pressures during entry to adhere strongly to their professional mandate, including the strict exercise of independence. The result is tense auditor–client relations and an increased likelihood of auditor turnover during the entry phase. Auditors that gain entry will “loosen up” and adjust their stance on independence due to the reduced entry pressures. As a result, the adjustment phase will witness a decline in auditor–client disagreements and a lower likelihood of auditor turnover. Over protracted periods, the audit process becomes tightly structured and recursive; the repetitive nature of the processes leads to audit fatigue, less attention to the independence mandate, and greater reliance on clients. The phenomenon portends an even further decline in auditor–client tension and a diminished likelihood of auditor turnover. These predictions are tested using auditor turnovers following auditor–client disputes as surrogates for auditor independence. The results confirm the life cycle phenomena and show that the level of auditor independence peaks during the early years of the auditors’ tenure and declines afterwards.
Ecological Security Evaluation System Integrated with Circuit Theory for Regional Ecological Security Pattern Construction: A Coordinated Study of Chang-Zhu-Tan Metropolitan Area in China
Authors: Wu Tingke , Lu Shiwei , Ding Yichen
Published: January 2025

Rapid urbanization and land use changes have brought enormous pressure onto the ecological environment. Constructing ecological security patterns (ESPs) contributes to scientifically utilizing ecosystem functions, maintaining biodiversity, and protecting the ecological environment. Thus, this study proposed a regional ESP construction framework, which integrated circuit theory with an ecological security evaluation system composed of a landscape connectivity analysis, an ecosystem service evaluation, and an ecological sensitivity analysis, to generate the ESP of the national-level Chang-Zhu-Tan Metropolitan Area (CZTMA). The results showed that (1) there were 22 ecological sources mainly consisting of woodlands, grasslands, and water bodies and distributed heterogeneously from the eastern to western CZTMA; (2) 48 ecological corridors connected the large-scale ecological patches such as rivers, lakes, wetlands, and woodlands in the CZTMA, and the average distance of the east side was shorter, while the distance of the west side was longer; and (3) 13 ecological pinch nodes and 28 ecological barrier nodes were identified as important nodes. On this basis, this research constructed a multi-level ESP consisting of “one center and multiple cores, one belt and two screens, multiple corridors and multiple nodes” for the CTZMA, which not only guarantees the stability of ecosystems but also maintains their efficiency in providing ecological services and their resistance to the pressure of human activities. Moreover, a series of specific recommendations for the optimization of regional ESPs were provided, including protection of ecological sources and enhancement of their habitat quality, improvement of ecological corridor connectivity, maintenance of pinch nodes, and restoration of barrier nodes. Coordinated mechanisms at the provincial level were proposed. This study could help with ecological conservation and restoration, and strategic planning making in integrated nature–human systems that cross administrative boundaries.
Influence of Perceived Restorativeness on Recovery Experience and Satisfaction with Walking Tourism: A Multiple-Group Analysis of Daily Hassles and the Types of Walking Tourist Attractions
Authors: Kim Song-I , Jeong Chul
Published: January 2025

This study aims to evaluate the restorative effects of walking tourism by investigating the influence of the perceived restorativeness of walking tourist attractions on recovery experience and satisfaction with walking tourism. Additionally, the study aims to determine any significant differences based on levels of daily hassles and types of walking tourist attractions as moderating variables. An online survey was conducted among walking tourists, focusing on Bukhansan National Park (mountainous), Haeparang Coastal Road and Namparang Coastal Road (coastal), and urban walking destinations, resulting in 330 valid responses. Results reveal that perceived restorativeness (being away, compatibility, fascination, coherence, and legibility) had a partially positive effect on recovery experience (restoration and emotional separation). Furthermore, recovery experience positively influenced walking tourism satisfaction. A multiple-group analysis indicated that, although no significant differences were found in the influence of perceived restorativeness on recovery experience based on daily hassle levels, the relationship between recovery experience and walking tourism satisfaction varied significantly depending on daily hassle levels. Additionally, the effects of perceived restorativeness on recovery experience and the impact of recovery experience on walking tourism satisfaction differed significantly among urban, mountainous, and coastal tourist attractions. These results provide valuable insights into the restorative effects of walking tourism and offer practical implications for tourism-related businesses, local governments, and managers.
Investigation of Spatio-Temporal Simulation of Mining Subsidence and Its Determinants Utilizing the RF-CA Model
Authors: Xu Jikun , Yan Chaode , Zhang Baowei , Chen Xuanchi , Yan Xu , Wang Rongxing , Yu Binhang , Boota Muhammad Waseem
Published: January 2025

It is important to carry out timely scientific assessments of surface subsidence in coal resource cities for ecological environmental protection. Traditional subsidence simulation methods cannot quantitatively describe the driving factors that contribute to or ignore the dynamic connections of subsidence across time and space. Thus, a novel spatio-temporal subsidence simulation model is proposed that couples random forest (RF) and cellular automaton (CA) models, which are used to quantify the contributions of driving factors and simulate the spatio-temporal dynamic changes in subsidence. The RF algorithm is first utilized to clarify the contributions of the driving factors to subsidence and to formulate transformation rules for simulation. Then, a spatio-temporal simulation of subsidence is accomplished by combining it with the CA model. Finally, the method is validated based on the Yongcheng coalfield. The results show that the depth–thickness ratio (0.242), distance to the working face (0.159), distance to buildings (0.150), and lithology (0.147) play main roles in the development of subsidence. Meanwhile, the model can effectively simulate the spatio-temporal changes in mining subsidence. The simulation results were evaluated using 2021 subsidence data as the basis data; the simulation’s overall accuracy (OA) was 0.83, and the Kappa coefficient (KC) was 0.71. This method can obtain a more realistic representation of the spatio-temporal distribution of subsidence while considering the driving factors, which provides technological support for land-use planning and ecological and environmental protection in coal resource cities.
Exploring Viral Interactions in Clavibacter Species: In Silico Analysis of Prophage Prevalence and Antiviral Defenses
Authors: Rubí-Rangel Lucía Margarita , León-Félix Josefina , Villicaña Claudia
Published: January 2025

Clavibacter is a phytopathogenic genus that causes severe diseases in economically important crops, yet the role of prophages in its evolution, pathogenicity, and adaptation remains poorly understood. In this study, we used PHASTER, Prophage Hunter, and VirSorter2 to identify prophage-like sequences in publicly available Clavibacter genomes. Prophage predictions were checked by hand to make them more accurate. We identified 353 prophages, predominantly in chromosomes, with some detected phage-plasmids. Most prophages exhibited traits of advanced domestication, such as an unimodal genome length distribution, reduced numbers of integrases, and minimal transposable elements, suggesting long-term interactions with their bacterial hosts. Comparative genomic analyses uncovered high genetic diversity, with distinct prophage clusters showing species-specific and interspecies conservation patterns. Functional annotation revealed prophage-encoded genes were involved in sugar metabolism, heavy metal resistance, virulence factors, and antibiotic resistance, highlighting their contribution to host fitness and environmental adaptation. Defense system analyses revealed that, despite lacking CRISPR-Cas, Clavibacter genomes harbor diverse antiviral systems, including PD-Lambda-1, AbiE, and MMB_gp29_gp30, some encoded within prophages. These findings underscore the pervasive presence of prophages in Clavibacter and their role in shaping bacterial adaptability and evolution.