bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerodynamic and Vibration Characteristics of Iced Power Transmission Conductors in a Nonuniform Wind Field Based on Unsteady Theory
Authors: Zhao Guifeng , Li Qingyang , Li Xiuyao , Zhang Meng
Published: January 2025

To study the aerodynamic and vibration characteristics of iced conductors under the influence of wind fluctuations, a harmonic superposition method is used to simulate nonuniform wind speeds. A user-defined function is written on the basis of the secondary development function of the Fluent 2021 R1 software to determine the displacement and velocity of the conductor at each time step, and a two-way fluid–structure interaction (FSI) numerical simulation of an iced conductor under a nonuniform wind field is performed via an overset mesh method. In the analysis, the aerodynamic coefficients and galloping characteristics of iced conductors under different degrees of freedom (DOFs) are investigated by considering different combinations of quasi-steady theory, unsteady theory, a uniform wind field, and a nonuniform wind field. The results show that in a nonuniform wind field, the mean, standard deviation (SD), and peak values of the drag and torsion coefficients of the conductors calculated via unsteady theory are significantly larger than those calculated via quasi-steady theory, indicating that the obtained aerodynamic coefficients of the latter (the mean values are typically used) conceal the characteristics of the iced conductors in an actual wind environment and ignore the adverse effects of the variability.
Quality of Consumed Energy as a Key Element in the Development of Processes of Energy Transformation in the European Union Countries
Authors: Bieszk-Stolorz Beata , Dmytrów Krzysztof , Pietrzak Michał Bernard
Published: January 2025

The process of energy transformation is one of the crucial elements of the process of improvement of the quality of consumed energy. The aim of the research is to assess the European Union countries in terms of the quality of their consumed energy and the speed of adaptation of this aspect of the energy transformation process. We assess the quality of consumed energy by means of the synthetic measure obtained by means of the dynamic version of the COmplex PRoportional ASsessment (COPRAS) method. We compare the countries with the dynamics of the energy transformation process by means of the dynamic time warping method and the hierarchical clustering. Obtained results indicate the best countries with respect to the quality of consumed energy were Malta, Austria, and Germany, and the worst ones—Poland, Czechia, and Slovakia. The process of energy transformation was evolving in the right direction—the quality of consumed energy increased. This increase was the fastest in Malta, Luxembourg, and Poland. The direction for future research is extending the set of variables to also consider other aspects of the energy transformation.
Multi-Scale Characterisation of the Fire Hazards of Timber Cladding
Authors: Hopkin Danny , Spearpoint Michael , Kanellopoulos Yorgos , Gorska Carmen , Mayfield Chris
Published: January 2025

Timber-clad facades, traditionally prevalent in North America and Scandinavia, are gaining popularity in central Europe and the UK for applications beyond low-rise buildings. Timber differs from typical cladding materials, such as masonry, due to its non-uniformity, combustibility, and moisture sensitivity, requiring unique design considerations to manage these characteristics. This paper investigates the fire hazards associated with timber cladding, particularly focusing on thermally modified timber, motivated by the 2019 Samuel Garside House fire in the UK. The study aims to address five key research questions: (1) the impact of thermal modification on external fire spread hazards, (2) the fire risk associated with slatted timber configurations, (3) the effectiveness of fire-retardant treatments, (4) the correlation between small-scale standard tests and large-scale behaviours, and (5) the adequacy of current fire safety guidance in addressing these hazards. The experimental campaign involved four timber sample variants: (i) virgin timber, (ii) new thermally modified timber, (iii) aged thermally modified timber, and (iv) fire-retardant-treated thermally modified timber. These samples were tested across four different methods, including the single-flame source test, mass loss cone test, single burning item (SBI) test, and an intermediate-scale test. Results indicated that thermal modification slightly increased the peak heat release rate (HRR) compared to virgin timber. The configuration of timber slats significantly impacted HRR, with vertically oriented slats demonstrating higher HRR than horizontally oriented flat cedar cladding. Fire-retardant treatments substantially reduced HRR, achieving Euroclass B in vertical slatted configurations. However, the long-term efficacy of these treatments under ageing and weathering conditions remains unexplored. This research underscores the need for clarifications in the guidance in timber cladding design, considering the observed fire hazards in different slat configurations and the efficacy of fire-retardant treatments.
Research Progress of Bioactive Peptides in Improving Type II Diabetes
Authors: Yu Jiaxin , Chen Guoxing , Jin Yan , Zhang Min , Wu Tao
Published: January 2025

Type II diabetes mellitus (T2DM) is a prevalent, long-standing metabolic condition marked by the body’s reduced response to insulin and inadequate insulin production, impacting a significant portion of the global population. Research has demonstrated that bioactive peptides play a crucial role in reducing blood sugar levels, enhancing insulin sensitivity, balancing lipid metabolism, and combating inflammation. These peptides also contribute to the enhancement of pancreatic islet function, lowering systemic inflammation by influencing various molecular signaling pathways. This paper provides an overview of recent advancements and potential applications of bioactive peptides in addressing T2DM. It highlights the diverse impacts of bioactive peptides sourced from different origins in combating diabetes. This comprehensive review offers theoretical substantiation and novel insights to support the future clinical utilization and exploration of bioactive peptides for T2DM management.
The Effects of Packaging Barrier Properties Coupled with Storage Temperatures on the Dominant Spoilage Bacteria Composition and Freshness Quality of Lamb
Authors: Wang Debao , Chai Xiaoyu , Wang Su , Zhao Tongtong , Zheng Xiaochun , Rao Weili , Yang Huiguo , Zhang Dequan , Hou Chengli
Published: January 2025

This study aims to establish a preservation method by coupling certain barrier packaging with storage temperatures suitable for extending the shelf of chilled lamb. Chilled lamb was packaged using three different oxygen permeability packaging materials of high-oxygen-barrier packaging (HORP), medium-oxygen-barrier packaging (MORP), and low-oxygen-barrier packaging (LORP) (1.70, 23.95, and 1631.44 cm3/(m2·24·h·0.1·MPa), respectively, then stored at temperatures of 4 °C and −1 °C for 28 days, respectively. The results of total viable count, pH, color, and volatile basic nitrogen indicate that HORP effectively inhibits the growth rate of surface microorganisms and the oxidation rate of proteins in lamb. The sulfhydryl content, carbonyl value, and electronic nose suggest that the oxidative decomposition rate of lamb during storage at −1 °C is lower compared to storage conditions at 4 °C. The microbial diversity suggests that HORP significantly hinders the growth and reproduction of Pseudomonas and Brochothrix aerobic spoilage bacteria, as well as diminishes the abundance of the dominant microbial community. Herein, utilizing high-barrier packaging with an oxygen permeability of lower than 1.70 cm3/(m2·24·h·0.1·MPa) in conjunction with ice temperature storage at −1 °C is a highly effective preservation method for prolonging the shelf life of chilled lamb to 28 days.
On Product Neutrosophic Fractal Spaces and α-Density Theory with Arbitrarily Small and Controlled Error
Authors: Ahmad Khaleel , Ishtiaq Umar , Murtaza Ghulam , Popa Ioan-Lucian , Maiz Fethi Mohamed
Published: January 2025

In this manuscript, we present the classical Hutchinson–Barnsley theory on the product neutrosophic fractal spaces by utilizing an iterated function system, which is enclosed by neutrosophic Edelstein contractions and a finite number of neutrosophic b-contractions. Further, we provide a sequence of sets that, under appropriate conditions and in terms of the Hausdorff neutrosophic metric, converge to the attractor set of specific neutrosophic iterated function systems. Furthermore, we present a fuzzy variant of α-dense curves that can accurately approximate the attractor set of certain iterated function systems with barely noticeable and controlled errors. In the end, we make a connection between the above-discussed concepts of neutrosophic theory and α-density theory.
Validation of the Arabic Chronic Rhinosinusitis Patient-Reported Outcome (CRS-PRO): Translation and Cultural Adaptation
Authors: Biadsee Ameen , Abu Amsha Natalie , Sowerby Leigh J. , Boldes Tomer , Kassem Firas
Published: January 2025

Background: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) is a newly developed, disease-specific questionnaire designed for patients with CRS. This study focused on translating the CRS-PRO into Arabic, conducting cross-cultural adaptation and validation of the questionnaire, and assessing its reliability and validity. Methods: This prospective study involved 112 patients divided into CRS, functional endoscopic sinus surgery (FESS), and control groups. Participants completed the questionnaire at enrollment and again after one month. The Arabic version of the CRS-PRO was created following the International Society for Pharmacoeconomics and Outcomes Research guidelines for translation and cross-cultural adaptation. Results: This study included 74 males (66.1%) and 38 females (33.9%), with an average age of 37.4 ± 14.8 years. The Arabic CRS-PRO questionnaire has high internal consistency and reliability (Cronbach’s alpha 0.97). It also has strong discriminant validity in distinguishing between groups (ANOVA, p < 0.001). The assessment of test/retest symptom scores and their consistency over time confirmed the reliability of the CRS-PRO in differentiating CRS patients from healthy individuals and in monitoring surgical outcomes. This was validated through Pearson’s correlation coefficients (p < 0.01) and intraclass correlation (p < 0.0001). Conclusions: The Arabic version of the CRS-PRO proved simple, reliable, and valid. It showed high internal consistency, reliability, and strong discriminant validity in distinguishing between healthy individuals, CRS patients, and those pre- and post-FESS.
Assessing the Risk of Antibiotic Resistance in Childhood Pneumonia: A Hospital-Based Study in Bangladesh
Authors: Zaman Sojib Bin , Hossain Naznin , Talha Md. Taqbir Us Samad , Hasan Kashfia , Zaman Rafid Bin , Khan Raihan
Published: January 2025

Background: Approximately two to three children die from pneumonia every hour, and pneumonia is the leading cause of hospitalization for children under five in Bangladesh. Bangladesh has adopted the Pocket Book guidelines by the World Health Organization (WHO) for hospital management of childhood pneumonia. These guidelines recommend the proper use of injectable antibiotic administration. Objectives: We assessed and compared the prescription drugs for treating childhood pneumonia following WHO guidelines in a secondary and tertiary hospital in Bangladesh. Methods: We conducted a cross-sectional comparative study among children under five years who were admitted to a tertiary hospital, Dhaka Medical College Hospital (DMCH), and a secondary-level hospital, Kushtia District Hospital (KDH), with pneumonia between May 2021 and May 2022. A structured questionnaire was administered to the eligible participants. Additionally, we reviewed the hospital records related to the patient’s treatment. SPSS (Version 28) was used to conduct statistical analysis. Results: 316 children were enrolled during the study period, of whom 66.4% were collected from DMCH. There were 65.8% and 24.6% of patients who were classified with severe pneumonia and very severe pneumonia, respectively. In DMCH, the severity of pneumonia percentage was 57.6%, while in KDH, the percentage was 82%. A significant difference was found between the two facilities in diagnosing complicated pneumonia, prescribing the appropriate antibiotics, and ensuring oxygen availability. Amoxicillin was prescribed to 83.5% of the participants, and ceftriaxone was used at a high rate (64.5–70.9%). Combining injections of ceftriaxone with oral amoxicillin or other combinations of antibiotics, both facilities used high frequencies of non-antibiotic corticosteroids. Conclusions: Antibiotics were overprescribed, and injections were prescribed at higher levels than WHO recommended. This could pose a threat to antibiotic resistance. There is a need to enforce standard prescribing policies and treatment guidelines to reduce morbidity and mortality among hospitalized children with pneumonia.
Pain Assessment and Management in Oncological Practice: A Survey from the Italian Network of Supportive Care in Oncology
Authors: Antonuzzo Andrea , Gonella Silvia , Blasi Livio , Carnio Simona , Franzese Ciro , Marano Luigi , Santini Daniele , Bossi Paolo
Published: January 2025

Background/Objectives: Cancer pain is prevalent across all stages of the disease, significantly impacting patients’ lives. Despite the availability of guidelines, its assessment and management remain suboptimal in many clinical settings. This study aimed to explore how healthcare professionals in Italy assess and manage cancer pain, identifying gaps and educational needs to improve adherence to best practices. Methods: A multidisciplinary Scientific Board designed an online survey comprising 28 items addressing demographics, pain assessment tools, perception of pain, pharmacological management, adverse effects, and barriers to care. The survey targeted oncologists, nurses, radiotherapists, and surgeons within the Italian Network of Supportive Care in Oncology. Data were collected from March to May 2024 and analyzed descriptively. Results: Eighty-five professionals participated, predominantly oncologists (63.5%). Most respondents utilized pain scales, with the Numerical Rating Scale (60.3%) being the most frequent. However, specific tools like the Edmonton Symptom Assessment System (ESAS) were underutilized, possibly due to limited training and time constraints. Factors influencing analgesic choice included patient comorbidities (30.3%) and polypharmacy (28.0%). The main barriers to effective pain management included inadequate training (85.5%) and poor communication between patients and caregivers (40.6%) and within care teams (31.9%). Preventive measures for opioid-induced adverse events were widely employed, with laxatives (52.7%) and antiemetics (40.5%) being the most common. Conclusions: Findings underscore the need for structured training programs, improved communication, and integration of validated assessment tools. A multidisciplinary, proactive approach to cancer pain assessment and management is essential to optimize care and reduce its burden across all disease stages.
The Effect of Wearing Elastic Compression Stockings on Leg Edema in Pregnant Women in Late Pregnancy as Determined by Measuring the Deep Venous Velocity and Flow
Authors: Mori Kanon , Koshiyama Masafumi , Watanabe Yumiko , Okamoto Noriko , Yanagisawa Nami , Banba Airi , Ikuta Eri , Ono Ayumi , Seki Keiko , Nakagawa Miwa , Sakamoto Shin-ichi , Hara Yoko , Nakashima Akira
Published: January 2025

Background: The present study evaluated the objective effectiveness of wearing compression stockings during late pregnancy on leg edema by measuring changes in venous velocity and blood flow. Methods: Using Doppler ultrasonography, we calculated the popliteal venous velocity and blood flow and compared them in the following four groups: (1) 13 non-pregnant women (26 legs) without leg edema, (2) 23 pregnant women (46 legs) in late pregnancy without leg edema, (3) 22 pregnant women (44 legs) in late pregnancy with leg edema who were followed up without treatment, and (4) 21 pregnant women (42 legs) in late pregnancy with leg edema who wore elastic compression stockings for 1 week. Results: Both the average velocity and blood flow of the popliteal vein of pregnant women’s legs in late pregnancy were significantly lower than those in non-pregnant women (6.32 ± 0.28 cm/s vs. 9.14 ± 0.37 cm/s; 118.48 ± 8.83 mL/min vs. 177.73 ± 11.74 mL/min, p < 0.0001, respectively). Furthermore, both the average venous velocity and blood flow in edematous legs in late pregnancy were significantly lower than those in non-edematous legs (5.32 ± 0.93 cm/s vs. 6.32 ± 0.28 cm/s; 82.68 ± 35.90 mL/min vs. 118.48 ± 8.83 mL/min, p < 0.0001, respectively). Finally, both the average venous velocity and blood flow were significantly higher in edematous legs in late pregnancy after wearing stockings than without treatment (7.69 ± 0.17 cm/s vs. 5.36 ± 0.17 cm/s; 143.22 ± 48.74 mL/min vs. 97.03 ± 40.07 mL/min, p < 0.0001, respectively). Conclusions: The wearing of elastic compression stockings by women with edematous legs in late pregnancy significantly increases the deep venous velocity and flow. Thus, it is possible to prevent deep vein thrombosis in this population.
Expression Pattern Analyzation and Regulation Genes Identification on the Purple Phenotype in the Different Tissues of the Purple Pak-choi and Zicaitai
Authors: Zhu Yating , Wang Xia , Tu Xiuping , Zhang Shujiang , Zhang Shifan , Zhang Hui , Sun Rifei , Xu Xiuxiu , Gao Xinyu , Li Guoliang , Li Fei
Published: January 2025

Among the Brassica species in China, including Chinese cabbage, pak-choi, caixin, zicaitai, and wucai, Brassica rapa plays an important role in vegetable production. Purple resources from the species itself are scarce. It is worth noting that the tissue positions expressing a purple phenotype vary greatly between purple pak-choi and zicaitai. In this study, the genetic patterns of the purple phenotype were analyzed in purple pak-choi and zicaitai, and the F1 showed purple leaves and green stems, which indicated that purple traits in the leaves and stem were inherited independently. In conjunction with field identification, RNA-seq was used to sequence the transcriptomes of the purple expression sites of purple pak-choi, zicaitai, and their F1. The high expression of the regulatory genes Dark_pur and BrTT8 affected the purple color of pak-choi and caused the high expression of structural genes of the anthocyanin metabolism pathway and the accumulation of anthocyanins in leaves. The regulatory genes BrPAP2 and BrTT8 affected the purple color of zicaitai stems, were significantly upregulated, and caused high expression of related structural genes, leading to the accumulation of anthocyanins in the stem epidermis. This suggested that BrPAP2 and Dark_pur were both R2R3-MYB transcription factors, which were tissue-specific for the regulation of purple color traits in B. rapa. They also had a gene epistatic effect, which influenced the expression of purple traits in the F1. The gene MYBL2 was highly expressed in all purple tissue sites. The present study on the regulatory genes of the purple phenotype of zicaitai and purple pak-choi provides a theoretical basis for revealing the influence of purple traits on B. rapa leaves and stems, and it may lay the foundation for the selection and breeding of purple vegetables of B. rapa.
The Interplay of Personality Traits and Psychological Well-Being: Insights from a Study of Italian Undergraduates
Authors: Orrù Graziella , Piarulli Andrea , Conversano Ciro , Grenno Giovanna , Gemignani Angelo
Published: January 2025

Objectives: The mental health and well-being of university students are crucial areas of research due to their significant impact on academic success, personal development, and overall life satisfaction. Since previous research consistently shows that the stress related to academic challenges can significantly affect mental health, the study aims to examine the relationship between personality traits, locus of control, and psychological well-being outcomes. Methods: In the present study, 67 Italian undergraduate students (19.45 ± 1.62 years) were evaluated to assess the connections between personality traits, locus of control, and key psychological outcomes including depression, anxiety, sleep disturbances, and subjective memory complaints. Results: The analyses of the collected variables revealed a strong interrelationship between stress, anxiety, depression, and insomnia, contributing to a general construct termed psychological well-being disturbances (PWBD). When considering the Big Five personality traits, a significant positive association with internal control and mindfulness levels was observed both for extraversion and conscientiousness, while neuroticism was associated with increased external control and subjective memory complaints. Conclusions: These findings highlight the importance of understanding personality traits in shaping psychological well-being and coping mechanisms among students. Educational institutions should consider incorporating personality-based approaches into their support systems, as fostering traits linked to better psychological well-being, such as extraversion, conscientiousness, and agreeableness, may help mitigate the negative impact of stress and anxiety commonly experienced in academic settings.
Glycosylation Pathways Targeted by Deregulated miRNAs in Autism Spectrum Disorder
Authors: Mirabella Federica , Randazzo Martina , Rinaldi Alessandro , Pettinato Fabio , Rizzo Renata , Sturiale Luisa , Barone Rita
Published: January 2025

Autism Spectrum Disorder (ASD) is a complex condition with a multifactorial aetiology including both genetic and epigenetic factors. MicroRNAs (miRNAs) play a role in ASD and may influence metabolic pathways. Glycosylation (the glycoconjugate synthesis pathway) is a necessary process for the optimal development of the central nervous system (CNS). Congenital Disorders of Glycosylation (CDGs) (CDGs) are linked to over 180 genes and are predominantly associated with neurodevelopmental disorders (NDDs) including ASD. From a literature search, we considered 64 miRNAs consistently deregulated in ASD patients (ASD-miRNAs). Computational tools, including DIANA-miRPath v3.0 and TarBase v8, were employed to investigate the potential involvement of ASD-miRNAs in glycosylation pathways. A regulatory network constructed through miRNet 2.0 revealed the involvement of these miRNAs in targeting genes linked to glycosylation. Protein functions were further validated through the Human Protein Atlas. A total of twenty-five ASD-miRNAs were identified, including nine miRNAs that were differentially expressed in cells or brain tissue in ASD patients and associated with glycosylation pathways, specifically protein N- and O-glycosylation and glycosaminoglycan biosynthesis (heparan sulfate). A number of CDG genes and/or ASD-risk genes, including DOLK, GALNT2, and EXT1, were identified as targets, along with validated interactions involving four key miRNAs (hsa-miR-423-5p, hsa-miR-30c-5p, hsa-miR-195-5p, and hsa-miR-132-5p). B4GALT1, an ASD susceptibility gene, emerged as a central regulatory hub, reinforcing the link between glycosylation and ASD. In sum, the evidence presented here supports the hypothesis that ASD-miRNAs mediate the epigenetic regulation of glycosylation, thus unveiling possible novel patho-mechanisms underlying ASD.
A Review of Immunological Evaluation of Patients with Recurrent Spontaneous Abortion (RSA)
Authors: Andreescu Mihaela , Tanase Alina , Andreescu Bogdan , Moldovan Cosmin
Published: January 2025

In approximately half of the recurrent spontaneous abortion (RSA) cases, the underlying cause is unknown. However, most unexplained miscarriages are thought to be linked to immune dysfunction. This review summarizes the current evidence regarding the immunological evaluations of patients with RSA, with potential implications for clinical research. The immune system plays a crucial role in the successful outcome of pregnancy, as it tolerates the semi-allogeneic fetus while offering protection to both the mother and fetus from pathogens. The maternal-fetal interface is the place where the crosstalk between various immune cells such as macrophages, dendritic cells, natural killer (NK) cells, and T cells takes place. An adequate balance is required between these immune cells for pregnancy to progress. In RSA, a dysregulation between these immune players is witnessed. For example, in RSA, NK cells are not increased but also undergo a change in their activity, manifested as cytotoxic decidual NK. Similarly, regulatory T cells, which are crucial for fostering a tolerant immune environment, are decreased in RSA women. Similarly, imbalances between T-helper (Th1, Th2, Th17) cell subsets have been implicated in RSA. Furthermore, the imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophage phenotypes has been documented, with studies indicating a predominance of M1 macrophages in RSA patients. Targeting immune imbalances with therapies such as immunoglobulin administration, TNF inhibitors, and anticoagulants may improve pregnancy outcomes in women with RSA.
Analysis of the Transcriptome Provides Insights into the Photosynthate of Maize Response to Salt Stress by 5-Aminolevulinic Acid
Authors: Jiang Ying , Li Min , Qian Yumei , Rong Hao , Xie Tao , Wang Shanshan , Zhao Hong , Yang Liangli , Wang Qingyun , Cao Yanyong
Published: January 2025

Salt stress is a significant environmental factor that impedes maize growth and yield. Exogenous 5-aminolevulinic acid (ALA) has been shown to mitigate the detrimental effects of various environmental stresses on plants. However, its regulatory role in the photosynthesis mechanisms of maize seedlings under salt stress remains poorly understood. Transcriptome sequencing and physiological index measurements were conducted on the leaves of the “Zhengdan 958” cultivar subjected to three different treatments. Differential expression analysis revealed 4634 differentially expressed genes (DEGs), including key transcription factor (TF) families such as NAC, MYB, WRKY, and MYB-related, across two comparisons (SS_vs_CK and ALA_SS_vs_SS). Significant enrichment was observed in the metabolic pathways related to porphyrin metabolism, photosynthesis-antenna proteins, photosynthesis, and carbon fixation in photosynthetic organisms. ALA treatment modulated the expression of photosynthesis-related genes, increased photosynthetic pigment content, and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), thereby mitigating the excessive accumulation of reactive oxygen species (ROS). Furthermore, ALA increased starch content under salt stress. These findings establish a foundational understanding of the molecular mechanisms through which ALA regulates photosynthesis under salt stress in maize seedlings. Collectively, exogenous ALA enhances maize’s salt tolerance by regulating photosynthesis-related pathways.
Poliprotect®, a Medical Device Made of Substances, Potently Protects the Human Esophageal Mucosa Challenged by Multiple Agents: Evidence from In Vitro and Ex Vivo Electrophysiological Models
Authors: Khalil Mohamad , Perniola Valeria , Lanza Elisa , Mahdi Laura , Sallustio Pierluca , Idone Valeria , Semeraro Daniela , Mastrodonato Maria , Testini Mario , Desaphy Jean-Francois , Portincasa Piero
Published: January 2025

The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to −33%). In contrast, low concentrations of PPRO (50–100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux.
Vascular Cell Adhesion Molecule 1 and E-Selectin as Potential Cardiovascular Risk Biomarkers in Psoriasis
Authors: Machoń Natalia Joanna , Zdanowska Natalia , Klimek-Trojan Paulina , Owczarczyk-Saczonek Agnieszka
Published: January 2025

Vascular cell adhesion molecule-1 (VCAM-1) and E-selectin are involved in different inflammatory diseases and may be potential cardiovascular risk biomarkers in psoriasis. They play an important role in regulating the recruitment and adhesion to endothelial cells during inflammation, affecting various conditions like vasculitis, atherosclerosis, and cardiovascular diseases. Positive outcomes have been observed when using Tumor Necrosis Factor Alpha (TNF-α) inhibitors and biological therapies that target selectins to control the functioning of endothelial cells and reduce inflammation in psoriasis and related conditions. Moreover, the effects of systemic treatments and ultraviolet B (UVB) phototherapy on VCAM-1 and E-selectin levels in psoriasis patients highlights the potential to impact the severity of psoriasis and activation of endothelial cells. In addition, various factors such as age, sex, metabolic syndrome, hyperglycemia, migraines, and tobacco smoking have been found to affect levels of VCAM-1 and E-selectin. This sheds light on understanding the complex relationship between endothelial activation and the development of diseases. Studies show the potential of using the levels of VCAM-1 and E-selectin as indicators of systemic treatment effectiveness and the progression of the disease. In summary, this review highlights the importance of VCAM-1 and E-selectin as potential biomarkers for assessing inflammation, disease severity and cardiovascular risk in individuals with psoriasis. The shared mechanisms of psoriasis and atherosclerosis, along with the effect of treatments on endothelial activation markers, provide significant insights for further research and approaches to manage inflammatory diseases in the future.
Characterization of the Activities of Vorinostat Against Toxoplasma gondii
Authors: Zeng Ting , Zhou Chun-Xue , Liu Dai-Ang , Zhao Xiao-Yan , An Xu-Dian , Liu Zhi-Rong , Qu Hong-Nan , Han Bing , Zhou Huai-Yu
Published: January 2025

Toxoplasma gondii is a globally widespread pathogen of significant veterinary and medical importance, causing abortion or congenital disease in humans and other warm-blooded animals. Nevertheless, the current treatment options are restricted and sometimes result in toxic side effects. Hence, it is essential to discover drugs that demonstrate potent anti-Toxoplasma activity. Herein, we found that vorinostat, a pan-HDAC inhibitor, exhibited an IC50 value of 260.1 nM against the T. gondii RH strain and a selectivity index (SI) > 800 with respect to HFF cells. Vorinostat disrupted the entire lytic cycle of T. gondii in vitro. Proteome analysis indicated that vorinostat remarkably perturbed the protein expression of T. gondii, and proteins involved in “DNA replication” and “membrane” were significantly dysregulated. Furthermore, we found that vorinostat significantly enhanced ROS production and induced parasite apoptosis. Importantly, vorinostat could prolong survival in a murine model. Our findings reveal that vorinostat is effective against T. gondii both in vitro and in vivo, suggesting its potential as a therapeutic option for human toxoplasmosis.
Development of a Vaccine Candidate Based on Surface-Displayed Particles of Mycobacterium tuberculosis from the MTB39A Protein
Authors: Wang Pu , Zhang Gang , Jiang Lingling , Zhang Sinong , Gao Weifeng , Wu Zhiwei , Li Yong
Published: January 2025

Tuberculosis (TB), a human and animal disease caused by Mycobacterium tuberculosis (M.tb), has the highest global mortality rate after coronavirus disease 2019 (COVID-19) and poses a major public health threat globally. Since 1890, vaccine candidates for various forms of TB have been developed for different age groups, but these vaccine candidates have not provided intended protection in adolescents and adults in clinical trials. To help prevent and control the spread of TB, the development of a safe and effective TB vaccine is imperative. The MTB39A protein and the molecular adjuvant MTB32C protein were expressed by an insect-baculovirus expression system, and the recombinant baculovirus surface-displayed particles were evaluated for their immunogenicity in BALB/c mice and calves. The results showed that the rvAc-71CA/rvAc-MTB39A recombinant baculovirus surface-displayed particles exhibited good immunogenicity in mice and calves and could be further developed as potential candidates.
Effects of Aging on Intramuscular Collagen-Related Factors After Injury to Mouse Tibialis Anterior Muscle
Authors: Kanazawa Yuji , Takahashi Tatsuo , Inoue Takao , Nagano Mamoru , Koinuma Satoshi , Eiyo Haruki , Tamura Yuma , Miyachi Ryo , Iida Naoya , Miyahara Kenichiro , Shigeyoshi Yasufumi
Published: January 2025

Collagen I is the most abundant type of intramuscular collagen. Lysyl oxidase promotes collagen cross-link formation, which helps stabilize the extracellular matrix. Furthermore, matrix metalloproteinases, responsible for collagen degradation, maintain typical muscle structure and function through remodeling. Although it is well known that aging leads to delayed recovery of muscle fibers, the impact of aging on the remodeling of intramuscular collagen is not well understood. In this study, we investigated the impact of aging on collagen remodeling during muscle injury recovery using young and old mouse models. Muscle injury was induced in the right tibialis anterior (TA) muscle of male C57BL/6J mice [aged 21 weeks (young) and 92 weeks (old)] using intramuscular cardiotoxin injection, with the left TA serving as a sham with saline injection. Following a one-week recovery period, aging was found to delay the recovery of the fiber cross-sectional area. The intensity and area of immunoreactivity for collagen I were significantly increased in old mice compared to young mice post-injury. Additionally, Lox expression and the number of LOX (+) cells in the extracellular matrix significantly increased in old mice compared to young mice post-injury. Furthermore, Mmp9 and MMP9 expression levels after muscle injury were higher in old mice than in young mice. These results suggest that muscle injury in old mice can lead to increased collagen I accumulation, enhanced collagen cross-link formation, and elevated MMP9 expression compared to young mice.
Fabrication of Hard Tissue Constructs from Induced Pluripotent Stem Cells for Exploring Mechanisms of Hereditary Tooth/Skeletal Dysplasia
Authors: Kondo Takeru , Thaweesapphithak Sermporn , Ambo Sara , Otake Koki , Ohori-Morita Yumi , Mori Satomi , Vinaikosol Naruephorn , Porntaveetus Thantrira , Egusa Hiroshi
Published: January 2025

Tooth/skeletal dysplasia, such as hypophosphatasia (HPP), has been extensively studied. However, there are few definitive treatments for these diseases owing to the lack of an in vitro disease model. Cells differentiated from patient-derived induced pluripotent stem cells (iPSCs) demonstrate a pathological phenotype. This study aimed to establish a method for fabricating hard tissue-forming cells derived from human iPSCs (hiPSCs) for the pathological analysis of tooth/skeletal dysplasia. Healthy (HLTH) adult-derived hiPSCs were cultured in a hard tissue induction medium (HM) with or without retinoic acid (RA) under 3D culture conditions, and mineralization and expression of dentinogenesis- and osteogenesis-related markers in 3D hiPSC constructs were evaluated. hiPSCs derived from patients with hypophosphatasia were also cultured in HM with RA. HLTH-derived hiPSCs formed mineralized 3D constructs and showed increased expression of dentinogenesis- and osteogenesis-related markers; addition of RA promoted the expression of these markers in hiPSC constructs. HPP-derived hiPSC constructs showed lower mineralization and expression of dentinogenesis- and osteogenesis-related markers than HLTH-derived hiPSCs, indicating an impaired ability to differentiate into odontoblasts and osteoblasts. This method for fabricating 3D hiPSC constructs allows for simultaneous assessment of dentinogenesis and osteogenesis, with HPP-derived hiPSC constructs recapitulating pathological phenotypes.
Novel Assignment of Gene Markers to Hematological and Immune Cells Based on Single-Cell Transcriptomics
Authors: Rosa Enrique De La , Alonso-Moreda Natalia , Berral-González Alberto , Sánchez-Luis Elena , González-Velasco Oscar , Sánchez-Santos José Manuel , Rivas Javier De Las
Published: January 2025

There are many different cells that perform highly specialized functions in the human hematological and immune systems. Due to the relevance of their activity, in this work we investigated the cell types and subtypes that form this complex system, using single-cell RNA sequencing (scRNA-seq) to dissect and assess the markers that best define each cell population. We first developed an optimized computational workflow for analyzing large scRNA-seq datasets. We then used it to find gene markers of the different cell types present in bone marrow (BM) and peripheral blood (PB). We analyzed three different single-cell datasets to find specific cell markers using this strategy: first, we searched in the CD marker genes and then in the genes encoding membrane proteins and finally in all detected protein-coding genes. This allowed us not only to confirm known CDs that best mark some cell types (e.g., monocytes, B cells, NK cells, etc.) but also to test the ability of new genes to distinguish specific cell types. Finally, we applied a machine learning method (Random Forest) to test the accuracy of the different markers we found. As a result of all this work, we have found and propose specific and robust gene signatures to identify different types and subtypes of hematological and immune cells.
Quantitative Trait Loci Identification and Candidate Genes Characterization for Indole-3-Carbinol Content in Seedlings of Brassica napus
Authors: Xiong Yiyi , Li Huaixin , Fan Shipeng , Ding Yiran , Wu Mingli , He Jianjie , Yan Shuxiang , Jia Haibo , Li Maoteng
Published: January 2025

Brassica napus is a member of the cruciferous family with rich glucosinolate (GSL) content, particularly glucobrassicin (3-indolylmethyl glucosinolate, I3M), that can be metabolized into indole-3-carbinol (I3C), a compound with promising anticancer properties. To unravel the genetic mechanism influencing I3C content in rapeseed seedlings, a comprehensive study was undertaken with a doubled haploid (DH) population. By quantitative trait loci (QTL) mapping, seven QTL that were located on A01, A07, and C04 were identified, with the most significant contribution to phenotypic variation observed on chromosome A07 (11.78%). The genes within the QTL confidence intervals (CIs) include transcription factors (TFs) and glycosyltransferases. After co-expression analysis, GSL-related regulatory network of TFs-targets was constructed and two TFs, BnaA07.ERF019 and BnaA07.NAC92, were identified as possible regulators in GSL biosynthesis. Three IGMT (glucosinolate methyltransferases) genes were found within the CIs that expressed higher in seedlings with more I3C, indicating their roles in I3C synthesis regulation. Molecular docking studies validated the binding capability of I3M to IGMTs, and those within the I3C QTL CIs have the strongest binding energy. These new discoveries offer critical insights into the genetic regulation of I3C content in rapeseed seedlings and establish a foundation for breeding high-I3C rapeseed varieties with potential health-promoting properties.
The Role of E3 Ubiquitin Ligase Gene FBK in Ubiquitination Modification of Protein and Its Potential Function in Plant Growth, Development, Secondary Metabolism, and Stress Response
Authors: Wu Yuting , Zhang Yankang , Ni Wanlin , Li Qinghuang , Zhou Min , Li Zhou
Published: January 2025

As a crucial post-translational modification (PTM), protein ubiquitination mediates the breakdown of particular proteins, which plays a pivotal role in a large number of biological processes including plant growth, development, and stress response. The ubiquitin-proteasome system (UPS) consists of ubiquitin (Ub), ubiquitinase, deubiquitinating enzyme (DUB), and 26S proteasome mediates more than 80% of protein degradation for protein turnover in plants. For the ubiquitinases, including ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), the FBK (F-box Kelch repeat protein) is an essential component of multi-subunit E3 ligase SCF (Skp1-Cullin 1-F-box) involved in the specific recognition of target proteins in the UPS. Many FBK genes have been identified in different plant species, which regulates plant growth and development through affecting endogenous phytohormones as well as plant tolerance to various biotic and abiotic stresses associated with changes in secondary metabolites such as phenylpropanoid, phenolic acid, flavonoid, lignin, wax, etc. The review summarizes the significance of the ubiquitination modification of protein, the role of UPS in protein degradation, and the possible function of FBK genes involved in plant growth, development, secondary metabolism, and stress response, which provides a systematic and comprehensive understanding of the mechanism of ubiquitination and potential function of FBKs in plant species.
Resilience of Spontaneously Hypertensive Rats to Secondary Insults After Traumatic Brain Injury: Immediate Seizures, Survival, and Stress Response
Authors: Komoltsev Ilia , Kostyunina Olga , Kostrukov Pavel , Bashkatova Daria , Shalneva Daria , Frankevich Stepan , Salyp Olga , Shirobokova Natalia , Volkova Aleksandra , Soloveva Aleksandra , Novikova Margarita , Gulyaeva Natalia
Published: January 2025

Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic–pituitary–adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs). Male adult SDRs and SHRs were subjected to lateral fluid-percussion injury. Immediate seizures were video recorded, corticosterone (CS) was measured in blood plasma throughout the study, and hippocampal morphology assessed 3 months post-TBI. Acute and remote survival rates were significantly higher in the SHRs compared to the SDRs (overall mortality 0% and 58%, respectively). Immediate seizure duration predicted acute but not remote mortality. TBI did not affect blood CS in the SHRs, while the CS level was transiently elevated in the SDRs, predicting remote mortality. Neuronal cell loss in the polymorph layer of ipsilateral dentate gyrus was found in both the SDRs and SHRs, while thinning of hippocampal pyramidal and granular cell layers were strain- and area-specific. No remote effects of TBI on the density of astrocytes or microglia were revealed. SHRs possess a unique resilience to TBI as compared with normotensive SDRs. SHRs show shorter immediate seizures and reduced CS response to the injury, suggesting the development of long-term adaptative mechanisms associated with chronic hypertension. Though remote post-traumatic hippocampal damage in ipsilateral dentate gyrus is obvious in both SHRs and SDRs, the data imply that physiological adaptations to high blood pressure in SHRs may be protective, preventing TBI-induced mortality but not hippocampal neurodegeneration. Understanding the mechanisms of resilience to TBI may also help improve clinical recommendations for patients with hypertension. Limitation: since more than a half of the SDRs with prolonged immediate seizures or elevated CS 3 days after TBI have died, survivorship bias might hamper correct interpretation of the data.
Synthesis and Anticancer Evaluation of O-Alkylated (E)-Chalcone Derivatives: A Focus on Estrogen Receptor Inhibition
Authors: Al-Ghamdi Alwah R. , Ahmed Wahid U. , Al-Wabli Reem I. , Al-Mutairi Maha S. , Rahman A. F. M. Motiur
Published: January 2025

Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of O-alkyl (E)-chalcone derivatives (4a–4v) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry. In vitro cytotoxicity assays revealed varying effectiveness, with compounds 4a, 4b, 4q, and 4v exhibiting potent activity against MDA-MB-231 and MCF-7, showing IC50 values between 2.08 and 13.58 µM, besides HCT-116 and HeLa cancer cell lines (IC50 values between 6.59 and 22.64 µM). Notably, compound 4b displayed remarkable selectivity, with an IC50 of 54.59 µM against the non-cancerous WI-38 cell line. Additionally, protein kinase inhibition assays indicated that compounds 4b and 4q effectively inhibited EGFR and VEGFR-2, with 4b outperforming the standard inhibitor erlotinib. Molecular docking studies of compound 4q showed strong binding affinities in the ATP-binding pockets of EGFR, HER2, VEGFR2, and CDK2. In silico analyses further highlighted the favorable pharmacokinetic properties of compound 4q, underscoring its potential as a selective tyrosine kinase inhibitor. These findings suggest the therapeutic promise of O-alkyl (E)-chalcone derivatives in cancer treatment.
Diagnostic and Therapeutic Utility of Extracellular Vesicles in Ocular Disease
Authors: Khristov Vladimir , Weber Sarah R. , Caton-Darby Mireille , Campbell Gregory , Sundstrom Jeffrey M.
Published: January 2025

Extracellular vesicles (EVs) are lipid bilayer particles released by virtually all cells, with prominent roles in both physiological and pathological processes. The size, number, and molecular composition of released EVs correlate to the cells of origin, modulated by the cell’s environment and pathologic state. The proteins, DNA, RNA, and protein cargo carried by EVs are protected by degradation, with a prominent role in targeted intercellular signaling. These properties make EVs salient targets as both carriers of biomarkers and potential therapeutic delivery vehicles. The majority of EV research has focused on blood, urine, saliva, and cerebrospinal fluid due to easy accessibility. EVs have also been identified and studied in all ocular biofluids, including the vitreous humor, the aqueous humor, and the tear film, and the study of EVs in ocular disease is a new, promising, and underexplored direction with unique challenges and considerations. This review covers recent advances in the diagnostic and therapeutic use of ocular EVs, with a focus on human applications and key preceding in vitro and in vivo animal studies. We also discuss future directions based on the study of EVs in other organ systems and disease sates.