bluuebunny/crossref_metadata_2025_split huggingface dataset:
SYNTHESIS, CHARACTERIZATION, AND LUMINESCENT PROPERTIES OF EUROPIUM(III) COMPLEXES WITH SALEN-TYPE LIGANDS CONTAINING 1,2,4-TRIAZOLE MOIETIES
Authors: Halushchenko Valeriia , Korovin Oleksandr , Smola Serhii , Bibik Yurii , Khomenko Dmytro , Doroshchuk Roman , Lampeka Rostyslav , Rusakova Natalya 
Published: January 2025

The study presents the synthesis, characterization, and photophysical investigation of novel Ln(III)complexes with 1,2,4-triazole-based Salen-type ligands, focusing on europium-centered optical pro­perties. An optimized synthetic method for Ln(III) complex formation was developed with the use of various salts, solvents, and deprotonating agents, with methanol, triethylamine, and triethylorthoformate yielding the best results. This approach produced light-yellow crystalline products with a 65–70% yield. Structural characterization through IR spectroscopy and mass spectrometry confirmed coordination by nitrogen and oxygen atoms, as evidenced by shifts in vibrational bands indicative of Eu–N bonds and alterationsin phenolic OH and CO stretching modes. UV-Vis absorption spectra revealed bathochromic shifts, indicating changes in electron density and increased conjugation resulting from complex formation. Upon excitation, the complexes exhibited fluorescence in the 400–500 nm range and phosphorescence in the 450–550 nm range, demonstrating effective energy transfer within the system. The CIE chromaticity coordinates for EuL1 (x=0,631, y=0,368) and EuL2 (x=0,603, y=0,396) denote a deep red emission with color purity and correlated color temperature (CCT) values of 2017,94 K and 1720,92 K, respectively, indicating their potential for high-purity red emissions in optoelectronic applications. Lifetime measurements (0,544 ms at 298 K and 0,706 ms at 77 K) indicate non-radiative relaxation processes that may be modulated by local symmetry, as suggested by the distinctive emission splitting in Eu(III) transitions. Emission spectra revealed prominent transitions typical of Eu(III) ions, with extensive splitting indicative of a low-symmetry environment, likely within C₂ᵥ or Cs point groups. Structural analysis supports a coordination number of 8, suggesting polyhedral arrangements like a bicapped trigonal prism. This synthetic route effectively produces Ln(III) complexes with tunable luminescent properties, revealing key structure-property relationships and enabling tailored red emissions, making these complexes promising precursors for display and lighting technologies.
Integrated bioinformatics analysis to explore potential therapeutic targets and drugs for small cell carcinoma of the esophagus
Authors: Zhu Maofei , Chu Yueming , Yuan Qiang , Li Junfeng , Chen Silin , Li Lin 
Published: January 2025

BackgroundSmall cell carcinoma of the esophagus (SCCE) is a rare form of esophageal cancer, which also belongs to the category of neuroendocrine malignant tumors, with a low incidence but high aggressiveness, and a very poor prognosis for patients. Currently, there is a lack of unique staging and treatment guidelines for SCCE. Therefore, a deeper understanding of the therapeutic targets and the mechanisms underlying its occurrence and development is of great importance for early diagnosis, identification of potential therapeutic agents and improvement of the prognosis for patients.MethodsFirstly, the dataset of SCCE was downloaded from the GEO database and GEO2R tool was employed for the analysis of differentially expressed genes (DEGs). GO and KEGG analysis of DEGs were carried out by using the Bioinformatics and OmicStudio tools. Then, up- and down-regulated genes were intersected with the oncogenes and the tumor suppressor genes respectively, to obtain the differentially expressed onco/tumor suppressor genes in SCCE. The STRING database was employed to conduct protein-protein interaction (PPI) analysis of differentially expressed onco/tumor suppressor genes, the network was further constructed in Cytoscape, and hub genes of the network were obtained through the Cytohubba plugin. In addition, miRDB, miRwalk, Targetscan, OncomiR, starbase, Lncbase were used to predict miRNAs and lncRNAs that regulate hub genes, the ceRNA network was built based on this. Transcription factor-miRNA co-regulatory network was analyzed in the NetworkAnalyst database and embellished in Cytoscape. Finally, drugs that may target hub genes were searched through the DGIdb and ConnectivityMAP, and docking verification was performed using Schrodinger.ResultsA total of 820 genes were upregulated and 716 were downregulated, of these, 54 were identified as oncogenes and 85 as tumor suppressor genes. Seven hub genes were identified from the PPI network, which were AURKA, BIRC5, CDK1, EZH2, FOXM1, KLF4 and UBE2C. Furthermore, a total of 38 drugs were searched and filtered in DGIdb and ConnectivityMAP, in the molecular docking results of drugs with hub genes, the docking score of AURKA, CDK1, and EZH2 with multiple drugs were low (&lt;6). In addition, crizotinib with AURKA, lapatinib with CDK1, rucaparib with EZH2, rucaparib with UBE2C were the lowest energy of all molecular docking results.ConclusionAURKA, BIRC5, CDK1, EZH2, FOXM1, KLF4 and UBE2C are the hub genes of SCCE, among them, AURKA, CDK1 and EZH2 may be used as targets of multiple drugs. Crizotinib, lapatinib, and rucaparib can act on the above targets to inhibit the progression of SCCE and play a therapeutic role.
Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
Authors: Lanto Jennifer , Vehlken Monika Maria Nicole , Abramenko Valeriia , Storch Alexander , Markert Franz 
Published: January 2025

Fetal neural stem cells (NSCs) physiologically reside under low-oxygen conditions (1%–5% of tissue pO2), but are often transferred and maintained under atmospheric oxygen levels of 21% pO2 (hyperoxia) for in vitro investigations. These altered oxygen conditions lead to adaptive changes in NSCs which complicate the interpretation of in vitro data. However, the underlying adaption dynamics remain largely enigmatic. Here we investigated short-term hyperoxia effects (5 days in 3% pO2 followed by 2 days in 21% pO2) in comparison to continuous hyperoxia effects (7 days in 21% pO2) and physioxic control (7 days in 3% pO2). We utilized cortical NSCs to analyze the cell cycle phases by flow cytometry and cumulative BrdU incorporation assay. NSCs showed a severe reduction of cell proliferation when cultivated under continuous hyperoxia, but no changes after short-term hyperoxia. Subsequent cell cycle analysis as assessed by flow cytometry revealed a clear shift of NSCs from G0/G1-phase towards S- or G2/M-phase after both continuous and short-term hyperoxia. However, while cell cycle length was dramatically reduced by short-term hyperoxia, it was increased during continuous hyperoxia. Taken together, our results demonstrate the beneficial effect of physioxia for expanding NSCs in vitro and reveal differential effects of short-term hyperoxia compared to continuous hyperoxia.
Corynebacteria from the respiratory microbiota modulate inflammatory responses and associate with a reduced pneumococcal burden in the lungs
Authors: Bergenfelz Caroline , Do Phuong , Larsson Liv , Ivarsson Hanna , Malmborn Kasper , Håkansson Anders P. 
Published: January 2025

BackgroundCertain species from the normal respiratory tract microbiota have recently been proposed to positively influence human health. Corynebacterium propinquum and C. pseudodiphtheriticum (Corynebacteria) are two Gram-positive species that frequently colonize the upper respiratory tract and strongly associate with a reduced incidence of respiratory tract infections. The specific role of Corynebacteria during respiratory health and disease is, however, largely uncharacterized.MethodRespiratory tract epithelial cells NCI-H292 and BALB/cByJ mice were inoculated with Corynebacteria (C. propinquum 2018M3 and 2019M4, and C. pseudodiphtheriticum 2019M8 and 2020M12) alone or with subsequent challenge with Streptococcus pneumoniae (pneumococci). The inflammatory response and the bacterial burden of both species over time were determined by Western blot, luciferase assay, cytokine bead array, flow cytometry and viable plate counts on blood agar plates.ResultsClinical isolates of Corynebacteria were well tolerated by human cells and mice. Corynebacteria induced a transient inflammatory response during healthy conditions in the absence of known pathogens. Pre-exposure or nasal priming with Corynebacteria did not affect subsequent acquisition of pneumococci but were associated with a modulated inflammatory response in vitro and in vivo as well as with a reduced pneumococcal burden in the respiratory tract of mice. This indicates that the presence of C. propinquum or C. pseudodiphtheriticum may protect against severe pneumococcal infections.ConclusionsIn this study, we delineate the role of Corynebacteria from the normal microbiota that epidemiologically associate with respiratory health. We show that the presence of Corynebacteria modulates the inflammatory response to pneumococci and associate with faster decrease in pneumococcal burden, primarily in the lower respiratory tract. Our data indicate that Corynebacteria has potential to protect against severe pneumococcal infections.
Saussurea costus alleviates ulcerative colitis by regulating the gut microbiota and improving intestinal barrier integrity
Authors: Pang Wen-lin , Li Tian-gang , Wang Yin-ying , Song Li-yun , Li Li , Li Xiao-ya , Qiu Yong , Yang Zhong-shan 
Published: January 2025

IntroductionThe global health challenge of ulcerative colitis (UC) has been classified by the WHO as a modern refractory disease, commonly referred to as green cancer, with limited treatment options still available, highlighting the urgent need for the development of new therapeutic strategies. Recent pharmacological research has shown that traditional Chinese medicine saussurea costus (SC) possesses beneficial antibacterial and anti-inflammatory properties. Nevertheless, its underlying mechanism remains elusive.MethodsFirstly, we identified the main active components of SC through UHPLC-QTOF-MS analysis. Subsequently, UC mice were induced using DSS and administered different doses of SC to evaluate its efficacy. Additionally, the impact of SC on the repair of the intestinal mucosal barrier was evaluated through immunofluorescence and western blot. Furthermore, 16s rRNA gene sequencing was conducted to elucidate the contribution of gut microbiota to UC pathogenesis.ResultsThe primary components of SC include Proline, Phenylalanine, Isoleucine, Lucidenic acid M, and Pyroglutamic acid. The efficacy of SC was concurrently assessed, revealing its potential to ameliorate histological injury in colitis mice. Furthermore, SC was found to decrease levels of TNF-α, IL-1β, IL-8, and IL-18 while promoting the expression of IL-10 and IL-22. Similarly, we also found that the expression of ZO-1 and Occludin was reversed by SC in colitis mice. In addition, analysis of 16S rRNA gene sequencing indicated that SC reduced harmful bacterial populations, such as Proteobacteria, while simultaneously enhancing the levels of beneficial bacteria like Lactobacillus, thereby contributing to the improvement of UC pathology.ConclusionThis study highlights the therapeutic potential of SC in managing UC through its ability to attenuate inflammatory responses, restore intestinal barrier functionality, and modulate gut microbiota composition, which findings offer insights into potential strategies for advancing UC treatment.
Detection and characterization of bovine hepacivirus in cattle and sheep from Hulunbuir, northeastern China
Authors: Ma Jingge , Wei Zhiwei , Li Liang , Wang Wei , Liu Ziyan , Liu Ning , Wei Feng , Zheng Xiangyu , Wang Zedong 
Published: January 2025

BackgroundBovine hepacivirus (BovHepV) is a recently identified member of the expanding genus Hepacivirus within the family Flaviviridae. However, the genetic diversity, geographical distribution, and host range of the virus remains poorly understood.MethodsIn this study, serum samples from cattle and sheep were obtained in Hulunbuir and pooled to establish RNA libraries, which were then analyzed using transcriptome sequencing. BovHepV-positive samples were confirmed using semi-nested PCR with primers designed based on the obtained viral sequences. Comprehensive bioinformatics analyses were employed to assess sequence similarity, phylogenetic evolution, and recombination of the obtained viral strains.ResultsA total of 988 serum samples from sheep (520) and cattle (468) were collected from 12 administrative districts in Hulunbuir from June to August, 2022. Semi-nested PCR revealed 6 BovHepV-positive districts with prevalence ranging from 2.0% to 35.0% in cattle, and one BovHepV-positive district with prevalence of 2.5% in sheep. The nucleotide sequence identities between viral strains from sheep and cattle ranged from 91.3% to 93.8%, while the amino acid sequence identities were between 95.4% and 96.7%. Phylogenetic analyses classified the obtained BovHepV strains within subtype G, genotype 1. Recombination analysis revealed the intergenerational relationships among the viral strains obtained from cattle and sheep.ConclusionWe identified genetic diversity in subtype G strains in cattle and detected a BovHepV strain in a sheep for the first time in northeastern China, confirming cross-species transmission and co-circulation between cattle and sheep, thus expanding the virus’s host range.
Vitamin A family suppresses periodontitis by restoring mitochondrial metabolic reprogramming in macrophages through JAK-STAT pathway
Authors: Cheng Zishuo , Huang Shun , Tang Qiya , Zhang Danlan , Huang Lan 
Published: January 2025

ObjectiveMitochondrial metabolic reprogramming in macrophages is crucial in the development and progression of inflammation. Given vitamin A’s antioxidant properties and its therapeutic effects on inflammation, this study aims to elucidate how vitamin A influences mitochondrial metabolic reprogramming in inflammatory states, specifically in periodontitis, through genetic bioinformatics and experimental methods.MethodThe study utilized the GSE16134 dataset from the Gene Expression Omnibus (GEO) database, focusing on human periodontitis. Vitamin A-targeted genes (ATGs) were identified and analyzed using CIBERSORT to explore their role in inflammation. Cluster analysis revealed two phenotypes associated with ATGs, showing differential expression of genes like COX1, IL-1β, and STAT3, and immune activation patterns. Weighted Gene Co-expression Network Analysis (WGCNA) identified 145 markers correlated with ATG-guided phenotypes and inflammation. Machine learning models, combined with Gene Set Variation Analysis (GSVA), identified five key genes (RGS1, ACAT2, KDR, TUBB2A, TDO2) linked to periodontitis. Cell Type-Specific Enrichment Analysis (CSEA) highlighted macrophages as critical in metabolic reprogramming, validated by external datasets with an AUC of 0.856 in GSE10334 and 0.750 in GSE1730678. Experimental validation showed vitamin A’s role in suppressing endoplasmic reticulum stress and altering mitochondrial dynamics, as well as metabolic reprogramming influencing inflammation via the STAT3 pathway in RAW 264.7 cells.ResultsThe study identified 13 differentially expressed ATGs in periodontitis, showing strong correlations with inflammation, particularly in plasma cells, macrophages, dendritic cells, neutrophils, and mast cells. Two ATG-guided phenotypes were identified, differing in gene expression and immune activation. WGCNA and machine learning models identified 145 markers and five key genes associated with periodontitis. GSVA and CSEA analyses highlighted the JAK-STAT pathway and macrophage involvement in metabolic reprogramming. Experimental data confirmed vitamin A’s effects on mitochondrial dynamics and metabolic reprogramming through the STAT3 pathway.ConclusionThe study demonstrates that vitamin A’s therapeutic effect on periodontitis is mediated through JAK-STAT pathway-guided mitochondrial metabolic reprogramming in macrophages. It identifies two genetic and immune-related phenotypes and five genetic identifiers associated with periodontitis risk.
Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches
Authors: Sethi Guneswar , Kim Young Kyu , Han Su-Cheol , Hwang Jeong Ho 
Published: January 2025

IntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.MethodsAn immunoinformatics approach was employed to design a multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were selected from five key Leptospira proteins. These epitopes were fused with a heparin-binding hemagglutinin (HBHA) adjuvant and appropriate linkers to construct the broad-spectrum vaccine. The physicochemical properties of the vaccine were assessed, including antigenicity, immunogenicity, allergenicity, and conservation. The vaccine’s 3D structure was modeled, optimized, and validated. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were performed to assess the vaccine's binding interactions with Toll-like receptors (TLR2 and TLR4). Immune simulations and in silico cloning were also conducted to evaluate the vaccine’s immune response and expression potential.ResultsThe MESV demonstrated high antigenicity, immunogenicity, non-allergenicity, and conservation across different Leptospira strains. Population coverage analysis revealed that T-cell epitopes significantly interacted with HLA molecules, covering 95.7% of the global population. Molecular docking showed strong and stable binding with TLR2 and TLR4, with binding energies of -1,357.1 kJ/mol and -1,163.7 kJ/mol, respectively. Molecular dynamics simulations and MM-GBSA analysis confirmed the stability of these interactions and accurately calculated the intermolecular binding free energies. Immune simulations indicated robust B and T cell responses, and in silico cloning demonstrated that the vaccine could be successfully expressed in E. coli.DiscussionThese findings suggest that MESV is a promising candidate for leptospirosis prevention, providing robust immune responses and broad population coverage. However, further in vivo studies are necessary to validate its efficacy and safety.
Immune cells in thyroid adenoma and carcinoma: uncovering a hidden value of assessing tumor-host interplay and its potential application in thyroid cytopathology
Authors: Omelianenko Iryna , Kobyliak Nazarii , Falalyeyeva Tetyana , Seleznov Oleksii , Botsun Pavlina , Ostapchenko Lyudmila , Korotkyi Oleksandr , Domylivska Liudmyla , Tsyryuk Olena , Mykhalchyshyn Galyna , Shapochka Tetiana , Sulaieva Oksana 
Published: January 2025

IntroductionAlthough the role of tumor immune microenvironment (TIME) in thyroid cancer is well established, little data exists about the differences in immune cell presence in thyroid adenomas and carcinomas. We assume that immune cell density could be an additional diagnostic criterion for differentiating benign and malignant tumors in thyroid aspirates.AimThe current study compared the immune contexture of thyroid adenoma (TA) and thyroid carcinoma (TC) in histological and cytological specimens of III-V categories.Materials and methodsThis pilot study included 72 cases (36 of TA and 36 of TC) with verified histological diagnosis and pre-operative cytology corresponding to categories III, IV and V according to the Bethesda system for reporting thyroid cytology. The number of CD8+, CD68+ and CD163+ cells was assessed in histological samples of TA and TC with further comparison to cytological specimens. Besides, the expression of STAT6 and SMAD4 as potential regulators of TIME was evaluated in the study.ResultsTC demonstrated an immune-rich profile representing abundant tumor-associated CD8+ lymphocytes, CD68 and CD163+ macrophages. In contrast, TA represented mostly a low immune cell infiltration. The higher immunogenicity of TC was accompanied by the more profound expression of STAT6 and SMAD4 in tumor cells. The number of immune cells in cytological specimens correlated with CD8+ (r = 0.693; p &lt; 0.001) and CD163+ cells (r = 0.559; p &lt; 0.001) in histological samples, reflecting the differences in the tumor immune microenvironment between benign and malignant thyroid neoplasms.ConclusionTC demonstrated high immunogenicity compared to TA, which correlated to the number of immune cells in cytological specimens. The number of immune cells in thyroid cytology samples could be an additional criterion in cytological diagnostics for III-V Bethesda categories. Further investigations are needed to validate the findings of the study.
A resting-state fMRI cross-sectional study of cardiorespiratory fitness decline after stroke
Authors: Qu Qingming , Zhang Kexu , Wang Hewei , Zhu Jie , Lin Yingnan , Jia Jie 
Published: January 2025

ObjectiveThe present study aimed to investigate alterations in neural activity and reorganization of functional networks within critical brain regions associated with reduced cardiorespiratory fitness (CRF) in stroke patients. By employing resting-state functional magnetic resonance imaging (fMRI), we sought to identify specific brain areas that may be implicated in CRF decline among this patient population.MethodsA total of 22 patients with stroke and 15 healthy subjects matched for age, gender, and body mass index were recruited. Rehabilitation assessments included peak oxygen uptake (VO2peak), peak work-rate, 10-meter walk test (10mWT), five times sit-to-stand test (FTSST), and 6-min walking distance (6MWD). Resting-state fMRI data were collected for the two groups, and correlation between changes in the amplitude of low-frequency fluctuations (ALFF) and CRF was analyzed to detect brain regions related to CRF and local neural activity in patients with stroke. On the basis of ALFF analysis, brain network analysis was performed, and the CRF-related brain regions in patients with stroke were selected as seed points. Functional connectivity (FC) analysis was the used to identify brain regions and networks potentially associated with CRF in patients with stroke.ResultsPatients with stroke exhibited significantly lower VO2peak, peak work-rate, 10mWT, and 6MWD compared to healthy controls (p &lt; 0.001). FTSST was significantly higher in patients with stroke than healthy controls (p &lt; 0.001). ALFF analysis identified CRF-related brain regions in patients with stroke, including the ipsilesional superior temporal gyrus (r = 0.56947, p = 0.00036), middle frontal gyrus (r = 0.62446, p = 0.00006), and precentral gyrus (r = 0.56866, p = 0.00036). FC analysis revealed that the functional connectivity of brain regions related to CRF in patients with stroke involved the ipsilesional M1 to ipsilesional precentral gyrus and contralesional postcentral gyrus, and the correlation coefficients were r = 0.54802 (p = 0.00065) and r = 0.49511 (p = 0.0025), respectively. The correlation coefficients of ipsilesional middle frontal gyrus to contralesional middle frontal gyrus, angular gyrus and ipsilesional superior frontal gyrus were r = 0.58617 (p = 0.00022), r = 0.57735 (p = 0.00028), and r = −0.65229 (p = 0.00002), respectively.ConclusionThis study observed that CRF levels were lower in stroke patients compared to those in healthy individuals. Resting fMRI analysis was applied to identify CRF-related brain regions (ipsilesional superior temporal, middle frontal, precentral gyri) and networks in patients with stroke.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=151095.