bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing Ascidians as Model Organisms for Environmental Risk Assessment
Authors: Rosner Amalia , Rinkevich Baruch
Published: October 2024

Environmental Risk Assessment (ERA) often relies on a restricted set of species as bio-indicators, introducing uncertainty when modeling complex environmental variables. This may lead to oversimplified or erroneous risk assessments. Ascidians, marine filter-feeding sessile chordates, are valuable models for scientific research in various biological fields such as stem cell biology, embryogenesis, regeneration, innate immunity, and developmental biology. Their global distribution, sensitivity to pollutants, high abundance, mass sexual reproduction, and habitation in coastal areas impacted by anthropogenic pollution make them excellent indicators for monitoring marine pollution and global environmental changes, including biological invasions and species diversity diminution cases. Despite their potential as environmental bioindicators, ascidians remain underutilized in ERAs (≤0.13% of ERA studies), particularly in the field of chemical pollution impact assessment, primarily due to a lack of standardization. This underrepresentation poses a challenge for accurate modeling, especially in models relying on a broad range of species (e.g., Species Sensitivity Distributions). Given these constraints, expanding the use of ascidians in ERAs could improve the comprehension and precision of environmental changes and their assessments. This underscores the necessity for future research to establish standardized testing protocols and choose the most suitable ascidian species for inclusion in ERAs.
A Review of Antimicrobial Peptides: Structure, Mechanism of Action, and Molecular Optimization Strategies
Authors: Ma Xu , Wang Qiang , Ren Kexin , Xu Tongtong , Zhang Zigang , Xu Meijuan , Rao Zhiming , Zhang Xian
Published: October 2024

Antimicrobial peptides (AMPs) are bioactive macromolecules that exhibit antibacterial, antiviral, and immunomodulatory functions. They come from a wide range of sources and are found in all forms of life, from bacteria to plants, vertebrates, and invertebrates, and play an important role in controlling the spread of pathogens, promoting wound healing and treating tumors. Consequently, AMPs have emerged as promising alternatives to next-generation antibiotics. With advancements in systems biology and synthetic biology technologies, it has become possible to synthesize AMPs artificially. We can better understand their functional activities for further modification and development by investigating the mechanism of action underlying their antimicrobial properties. This review focuses on the structural aspects of AMPs while highlighting their significance for biological activity. Furthermore, it elucidates the membrane targeting mechanism and intracellular targets of these peptides while summarizing molecular modification approaches aimed at enhancing their antibacterial efficacy. Finally, this article outlines future challenges in the functional development of AMPs along with proposed strategies to overcome them.
The Protective Effects of Polygala tenuifolia and Tenuifolin on Corticosterone-Evoked Ferroptosis, Oxidative Stress, and Neuroinflammation: Insights from Molecular Dynamics Simulations and In Vitro Experiments
Authors: Xue Chaoyi , He Zhiyong , Zeng Maomao , Wang Zhaojun , Chen Qiuming , Qin Fang , Chen Mingmin , Ye Hui , Chen Jie
Published: October 2024

Excessive stress is a well-established contributor to neurological damage, insomnia, and depression, imposing a significant burden on individuals and society. This underscores the urgent need for effective stress-relief strategies. The main purpose of this study was to explore the protective effects of Polygala tenuifolia (PT) and its bioactive compound, tenuifolin, against corticosterone-induced neurotoxicity, with a focus on ferroptosis, oxidative stress, and neuroinflammation. Both PT extracts and tenuifolin mitigated corticosterone-induced cellular damage. Tenuifolin reversed the corticosterone-induced dysregulation of ferroptosis-associated proteins, such as SLC7A11, GPX4, and Nrf2, leading to a marked reduction in ferroptosis levels. Molecular dynamics simulations revealed that corticosterone significantly altered the conformation and binding energy of the SLC7A11/SLC3A2 complex, critical for ferroptosis regulation. These changes were reversed by tenuifolin. Additionally, tenuifolin alleviated corticosterone-induced oxidative stress and neuroinflammation, both of which accelerated ferroptosis. In conclusion, these results indicate that tenuifolin attenuates corticosterone-induced neurotoxicity by modulating ferroptosis, oxidative stress, and neuroinflammation. This study provides a theoretical foundation for the application of PT and tenuifolin in stress-induced nerve damage.
Assessment of Whole Grain Ancient Wheat Sourdough in Lyophilised and Native Forms for Cookie Formulation
Authors: Maravić Nikola , Pajin Biljana , Hadnađev Miroslav , Dapčević-Hadnađev Tamara , Pestorić Mladenka , Škrobot Dubravka , Tomić Jelena
Published: October 2024

This study explored the potential of two forms of sourdough—native and lyophilised—obtained through the spontaneous fermentation of whole grain flours from ancient wheat varieties, for cookie production. The research involved evaluated the dough’s rheological properties through creep and recovery measurements and Mixolab analysis, assessing proximate composition, physical attributes, texture, colour, and sensory characteristics using the Rate-all-that-apply (RATA) method. The rheological analysis revealed that native sourdough significantly impacted dough behaviour, making it more challenging to process. Although differences were observed in the proximate composition, colour, and texture, these factors did not influence the samples as much as the rheological parameters. Sensory evaluation identified Khorasan lyophilised sourdough, along with its control sample, as the most promising, while modern wheat, spelt, and emmer exhibited potentially undesirable attributes. Based on these findings, it was concluded that lyophilised Khorasan sourdough was very favourable for cookie production and should be considered for further in-depth research and development. This suggests that the lyophilised forms of ancient wheats could offer valuable alternatives for cookie formulation, with implications for both the processing and sensory attributes of the final product.
Metabolic Profiling and Stable Isotope Analysis of Wines: Pilot Study for Cross-Border Authentication
Authors: Miricioiu Marius Gheorghe , Ionete Roxana Elena , Costinel Diana , Simova Svetlana , Gerginova Dessislava , Botoran Oana Romina
Published: October 2024

Globalization and free market dynamics have significantly impacted state economies, particularly in the wine industry. These forces have introduced greater diversity in wine products but have also heightened the risk of food fraud, especially in high-value commodities like wine. Due to its market value and the premium placed on quality, wine is frequently subject to adulteration. This issue is often addressed through regulatory trademarks on wine labels, such as Protected Designation of Origin (PDO) and Protected Geographic Indication (PGI). In this context, the metabolic profiles (organic acids, carbohydrates, and phenols) and stable isotope signatures (δ13C, δ18O, D/HI, and D/HII) of red and white wines from four agroclimatically similar regions were examined. The study explored how factors such as grape variety, harvest year, and geographical origin affect wine composition, with a particular focus on distinguishing samples from cross-border areas. Multivariate statistical analysis was used to assess the variability in wine composition and to identify distinct groups of samples. Preliminary results revealed that organic acids and volatile compounds were found in lower concentrations than carbohydrates but were significantly higher than phenols, with levels ranging between 1617 mg/L and 6258 mg/L. Carbohydrate content in the wines varied from 8285 mg/L to 14662 mg/L. Principal Component Analysis (PCA) indicated certain separation trends based on the variance in carbohydrates (e.g., fructose, glucose, galactose) and isotopic composition. However, Discriminant Analysis (DA) provided clear distinctions based on harvest year, variety, and geographical origin.
Optimizing Fractional-Order Convolutional Neural Networks for Groove Classification in Music Using Differential Evolution
Authors: Chen Jiangang , Su Pei , Li Daxin , Han Junbo , Zhou Gaoquan , Tang Donghui
Published: October 2024

This study presents a differential evolution (DE)-based optimization approach for fractional-order convolutional neural networks (FOCNNs) aimed at enhancing the accuracy of groove classification in music. Groove, an essential element in music perception, is typically influenced by rhythmic patterns and acoustic features. While FOCNNs offer a promising method for capturing these subtleties through fractional-order derivatives, they face challenges in efficiently converging to optimal parameters. To address this, DE is applied to optimize the initial weights and biases of FOCNNs, leveraging its robustness and ability to explore a broad solution space. The proposed DE-FOCNN was evaluated on the Janata dataset, which includes pre-rated music tracks. Comparative experiments across various fractional-order values demonstrated that DE-FOCNN achieved superior performance in terms of higher test accuracy and reduced overfitting compared to a standard FOCNN. Specifically, DE-FOCNN showed optimal performance at fractional-order values such as v = 1.4. Further experiments demonstrated that DE-FOCNN achieved higher accuracy and lower variance compared to other popular evolutionary algorithms. This research primarily contributes to the optimization of FOCNNs by introducing a novel DE-based approach for the automated analysis and classification of musical grooves. The DE-FOCNN framework holds promise for addressing other related engineering challenges.
Fractal Calculus Facilitates Rethinking ‘Hard Problems’: A New Research Paradigm
Authors: West Bruce J.
Published: October 2024

This paper introduces a non-standard research technique to clarify how complex phenomena, such as those that are abundantly present in human physiology, can be faithfully described using fractal dynamical models with and without stochastic forces. This method for conducting research involves tracing the historical evolution of understanding an empirical medical process facilitated by the fractal-order calculus perspective. Herein, we trace the analysis of the time series for heart rate variability (HRV) developed for diagnosing the cardiovascular health of a patient. This is performed herein by introducing four (one empirical, which entails three theoretical fractal models) distinct but related fractal models, each one introduced to solve a particular problem arising from a fundamental defect in the previous model, but in generalizing a model at one stage to resolve the problem associated with the defect, another is invariably introduced by the replacement model. It is through the utilization of the fractal-order calculus that the necessity for rethinking how to systematically incorporate additional layers of complexity is revealed, ultimately resulting in a ‘complete’ description of its empirical dynamics in fractal terms.
Nonlinear Hydrophysical Disturbance Infragravity Sea Waves
Authors: Dolgikh Stanislav , Budrin Sergey , Pelinovsky Efim , Antonov Valery
Published: October 2024

An analysis of the behavior of the infra-gravitational sea wave revealed nonlinear hydrophysical disturbance of the “rogue waves” type. This disturbance is associated with transformation of sea waves when they move along a coastal marine area of decreasing depth, and with interaction with wind waves. These conclusions are confirmed through analysis of in situ data of the laser interference pressure meter of the hydrosphere in this paper and previous works. Full-scale data were obtained on the shelf of the Sea of Japan. During processing of in situ data, we focused on sea waves with periods ranging from 1 to 10 min.
Exploring the Effectiveness of Technology-Assisted Interventions for Promoting Independence in Elderly Patients: A Systematic Review
Authors: Albarqi Mohammed Nasser
Published: October 2024

Background: The aging global population presents significant challenges for healthcare systems. Technology-assisted interventions have emerged as promising tools to enhance independence and well-being among elderly individuals. Objective: The aim of this study was to evaluate the effectiveness of technology-assisted interventions in promoting independence among elderly patients and identify key barriers and facilitators to their implementation. Methods: A systematic review was conducted following PRISMA guidelines. Searches were performed in PubMed, IEEE Xplore, ACM Digital Library, Cochrane Library, and Scopus. Studies evaluating technology-assisted interventions for promoting independence in elderly patients were included. Data were synthesized through narrative and thematic analysis. Results: Fourteen studies met inclusion criteria. Technology-assisted interventions demonstrated positive impacts on physical and cognitive functioning, health management, quality of life, and technological engagement among elderly patients. Improvements were observed in areas such as mobility, chronic disease management, mental health, and daily living activities. High usability and adherence rates were reported for well-designed interventions. However, challenges in user-centered design, personalization, and integration with existing healthcare systems were identified. Conclusions: Technology-assisted interventions show promise in promoting independence among elderly patients. Future research should focus on addressing identified challenges and conducting larger, long-term studies to confirm effectiveness and sustainability.
Job Satisfaction Among First-Generation Migrant Physicians in Anesthesiology and Intensive Care Medicine in Germany
Authors: Elnahas Mahmoud , Hübner Jutta , Lang Philip M. , Ahmadi Emadaldin
Published: October 2024

Background/Objectives: This study examines job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesiology and intensive care medicine in Germany, comparing them to their native German counterparts. Methods: A cross-sectional survey design was utilized, collecting data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. Results: The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Migrant physicians reported higher difficulty and frustration in working with patients. Well-being items indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. Notably, the multivariate analyses of the total scale scores did not show significant associations between migration background and the overall outcome scales. Conclusions: The findings indicate unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.
Advancing Pharmaceutical Care in Community Pharmacies in Poland: A Blueprint for Enhanced Patient Care Quality
Authors: Merks Piotr , Kowalczuk Anna , Howell Aleksandra , Białoszewski Artur , Strocka Justyna , Krajewska Ewa , Pinkas Jarosław , Ostrowski Janusz , Staniszewska Anna , Neumann-Podczaska Agnieszka , Brzozowska Melania , Augustynowicz Anna , Borowska Mariola , Drab Agnieszka , Herda Jolanta , Kaźmierczak Justyna , Religioni Urszula
Published: October 2024

Background: This article reviews the current state of pharmaceutical care in community pharmacies in Poland and proposes a collaborative framework for its advancement. While pharmaceutical care has evolved significantly worldwide, with Europe leading the way, Poland has lagged in its development. Although Polish pharmacists are well-qualified and community pharmacies are numerous, pharmaceutical care remains underdeveloped. Methods: We conducted a literature review and analyzed case studies from European countries with advanced pharmaceutical services. Based on these findings, we collaborated with policy makers, commissioners, and academics to develop a framework for enhancing pharmaceutical care in Poland. The plan emphasizes integrating seven key services into Polish community pharmacies. Results: Our proposed framework outlines seven essential pharmaceutical services: medicine use reviews, new medicine services, minor ailment services, repeat prescription services, integrated prevention programs, cardiovascular disease prevention programs, and vaccination programs. Evidence from other European countries suggests that implementing these services could significantly improve health outcomes and patient quality of life. This is particularly important in light of Poland’s ageing population, the rising prevalence of chronic diseases, and the healthcare system’s increasing burden due to polypharmacy. Conclusions: The proposed framework presents a practical and collaborative approach to advancing pharmaceutical care in Poland. By adopting these key services, community pharmacies could play a more integral role in improving patient care quality and alleviating pressure on the broader healthcare system.
Telehealth Outreach Program for Child Traumatic Stress: Strategies for Long-Term Sustainability
Authors: Johnson Emily , Kruis Ryan , Orengo-Aguayo Rosaura , Verdin Rebecca , King Kathryn , Ford Dee , Stewart Regan
Published: October 2024

Background: There are high documented rates of exposure to traumatic events and mental health disorders among youths yet existing disparities in access to care for racial and ethnic minority youths and youths in rural communities. Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an evidence-based behavioral health therapy for children. The delivery of TF-CBT via telehealth can decrease access to care barriers. An interdisciplinary clinical team developed a training program to guide clinicians to effectively provide TF-CBT via telehealth. The goal of this study was to describe variation in implementation processes of the telehealth TF-CBT program and identify barriers and facilitators to program implementation post-training, which were utilized to develop implementation strategies for intervention sustainability. Methods: Using a mixed-methods approach, data were collected on telehealth implementation processes and facilitators and barriers to the delivery of telehealth TF-CBT. This study was guided by an adapted implementation science framework, namely the Exploration, Preparation, Implementation, Sustainment model. Interviews and surveys were completed with clinical site leaders who had participated in the telehealth TF-CBT training. Results: Throughout clinical sites, there was varied adoption and penetration of the telehealth TF-CBT program. Facilitators to implementation included leadership and site staff buy in, community needs, and training resources, while barriers included funding, available logistical resources, and child and family involvement. Conclusions: The feedback gained from this project assisted in the development of implementation strategies for increased adoption and sustainment of TF-CBT delivered via telehealth. Strategies include ongoing interactive assistance and resource support, enhanced training for stakeholders, and program adaptations, with the goal to increase access to quality mental health care for underserved populations.
The Real Value of CSR Performance in the NEV Industry: Evidence from China
Authors: Wu Qing , Satjawathee Theeralak
Published: October 2024

Corporate social responsibility (CSR) is increasingly becoming a major concern for investors and consumers, prompting companies to devote more resources to community engagement to manage conflict and improve business performance. In this study, we conducted an empirical analysis with a sample of 385 listed companies in China’s new energy vehicle (NEV) industry to analyze the relationship between CSR performance and corporate value (CV). With the ordinary least squares (OLS) regression analysis, our study’s results show a positive relationship between the CSR performance of these companies and corporate value. In addition, our findings indicate a lagged effect in the relationship between CSR and CV. The mechanism analysis suggests that corporate CSR performance helps to improve corporate reputation, reduce financing constraints, and thus increase corporate value. Moreover, high analyst attention and information transparency can enhance the positive effects of corporate CSR. This study contributes to the existing literature and empirical evidence by exploring the correlation between CSR performance and firm value in the context of emerging countries and the NEV industry.
Alkaline Mineral Complex Water Attenuates Transportation-Induced Hepatic Lipid Metabolism Dysregulation by AMPKα-SREBP-1c/PPARα Pathways
Authors: Gan Linli , Guo Hongrui , Yang Qiyuan , Zhou Xueke , Xie Yue , Ma Xiaoping , Gou Liping , Fang Jing , Zuo Zhicai
Published: October 2024

Transportation, an unavoidable process in livestock farming, causes metabolic disorders in the body, which then lead to endocrine disruption, being immunocompromised, and growth suppression. Lipid metabolism dysregulation is a critical phenotype induced by transportation. The liver is a vital organ in lipid metabolism, with a role in both lipid synthesis and lipolysis. However, the specific mechanisms by which transportation affects hepatic lipid metabolism remain unclear. This study employed rats as a model to investigate the effects of transportation on hepatic lipid metabolism. Rats subjected to transportation showed altered serum lipid profiles, including decreased serum triglyceride (TG), low-density lipoprotein cholesterol (VLDL-C), and non-esterified fatty acid (NEFA) immediately after transportation (IAT) and serum total cholesterol (TC) on day 3, and increasing serum TG, TC, and low-density lipoprotein cholesterol (LDL-C) on day 10. Meanwhile, fatty droplets in the liver were also reduced at IAT and increased on days 3 and 10. Notably, transportation also affected hepatic-lipid-metabolism-related enzyme activities and signaling pathways, such as increased AMP-activated protein kinase alpha (AMPKα) phosphorylation and modulations in key proteins and genes related to lipid metabolism, decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) activities at IAT, and increased carnitine palmitoyl transferase 1 alpha (CPT-1α) at IAT and ACC and CPT-1α activities on days 3 and 10. Supplementation with alkaline mineral complex water (AMC) before and after transportation mitigated the adverse effects on hepatic lipid metabolism by modulating the AMPKα-SREBP-1c/PPARα pathway, enhancing lipid synthesis, and reducing the oxidative catabolism of fatty acids. AMC inhibited the transportation-induced activation of AMPKα and restored the balance of lipid-metabolism-related enzymes and pathways. These findings highlight AMC’s potential as a therapeutic intervention to alleviate transportation-induced lipid metabolism disorders, offering significant implications for improving animal welfare and reducing economic losses in livestock farming.
Molecular, Histological, and Functional Changes in Acta1-MCM;FLExDUX4/+ Mice
Authors: Sohn Solene , Reid Sophie , Bowen Maximilien , Corbex Emilio , Le Gall Laura , Sidlauskaite Eva , Hourde Christophe , Morel Baptiste , Mariot Virginie , Dumonceaux Julie
Published: October 2024

DUX4 is the major gene responsible for facioscapulohumeral dystrophy (FSHD). Several mouse models expressing DUX4 have been developed, the most commonly used by academic laboratories being ACTA1-MCM/FLExDUX4. In this study, molecular and histological modifications in the tibialis anterior and quadriceps muscles were investigated in this model at different time points. We investigated several changes that could be used as markers of therapeutic efficacy. Our results confirm the progressive muscular dystrophy previously described but also highlight biases associated with tamoxifen injections and the complexity of choosing the genes used to calculate a DUX4-pathway gene composite score. We also developed a comprehensive force test that better reflects the movements made in everyday life. This functional force–velocity–endurance model, which describes the force production capacities at all velocity and fatigue levels, was applied on 12–13-week-old animals without tamoxifen. Our data highlight that previously unsuspected muscle properties are also affected by the expression of DUX4, leading to a weaker muscle with a lower initial muscle force but with preserved power and endurance capacity. Importantly, this force–velocity–endurance approach can be used in humans for clinical evaluations.
Recent Progress on Plant Apomixis for Genetic Improvement
Authors: Xue Lihua , Zhang Yingying , Wei Fang , Shi Gongyao , Tian Baoming , Yuan Yuxiang , Jiang Wenjing , Zhao Meiqi , Hu Lijiao , Xie Zhengqing , Gu Huihui
Published: October 2024

Apomixis is a reproductive process that produces clonal seeds while bypassing meiosis (or apomeiosis) without undergoing fertilization (or pseudo-fertilization). The progenies are genetically cloned from their parents, retaining the parental genotype, and have great potential for the preservation of genes of interest and the fixing of heterosis. The hallmark components of apomixis include the formation of female gametes without meiosis, the development of fertilization-independent embryos, and the formation of functional endosperm. Understanding and utilizing the molecular mechanism of apomixis has far-reaching implications for plant genetic breeding and agricultural development. Therefore, this study focuses on the classification, influencing factors, genetic regulation, and molecular mechanism of apomixis, as well as progress in the research and application of apomixis-related genes in plant breeding. This work will elucidate the molecular mechanisms of apomixis and its application for plant genetic improvement.
7-Ketocholesterol Effects on Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells
Authors: Oliveira Beatriz Araújo , Levy Débora , Paz Jessica Liliane , de Freitas Fabio Alessandro , Reichert Cadiele Oliana , Rodrigues Alessandro , Bydlowski Sérgio Paulo
Published: October 2024

Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic (ALPL, RUNX2, BGLAP) and adipogenic markers (PPARƔ, C/EBPα) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα, did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases.
A Computational Pipeline Observes the Flexibility and Dynamics of Plant Cytochrome P450 Binding Sites
Authors: Kuvek Tea , Marcher Claudia , Berteotti Anna , Lopez Carrillo Veronica , Schleifer Klaus-Jürgen , Oostenbrink Chris
Published: October 2024

Binding site flexibility and dynamics strongly affect the ability of proteins to accommodate substrates and inhibitors. The significance of these properties is particularly pronounced for proteins that are inherently flexible, such as cytochrome P450 enzymes (CYPs). While the research on human CYPs provides detailed knowledge on both structural and functional level, such analyses are still lacking for their plant counterparts. This study aims to bridge this gap. We developed a novel computational pipeline consisting of two steps. Firstly, we use molecular dynamics (MD) simulations to capture the full conformational ensemble for a certain plant CYP. Subsequently, we developed and applied a comprehensive methodology to analyze a number of binding site properties—size, flexibility, shape, hydrophobicity, and accessibility—using the fpocket and mdpocket packages on MD-generated trajectories. The workflow was validated on human CYPs 1A2, 2A6, and 3A4, as their binding site characteristics are well known. Not only could we confirm known binding site properties, but we also identified and named previously unseen binding site channels for CYPs 1A2 and 2A6. The pipeline was then applied to plant CYPs, leading to the first categorization of 15 chosen plant CYPs based on their binding site’s (dis)similarities. This study provides a foundation for the largely uncharted fields of plant CYP substrate specificity and facilitates a more precise understanding of their largely unknown specific biological functions. It offers new insights into the structural and functional dynamics of plant CYPs, which may facilitate a more accurate understanding of the fate of agrochemicals or the biotechnological design and exploitation of enzymes with specific functions. Additionally, it serves as a reference for future structural–functional analyses of CYP enzymes across various biological kingdoms.
Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review
Authors: Masnikosa Romana , Cvetković Zorica , Pirić David
Published: October 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody–drug conjugates, chimeric antigen receptors, bispecific antibodies and T-cell engagers, and immune checkpoint inhibitors. Candidate drugs explored in ongoing clinical trials are coupled with diverse toxicity issues and refractoriness to drugs. According to the literature on DLBCL, the promise for new therapeutic targets lies in epigenetic alterations, B-cell receptor and NF-κB pathways. Herein, we present putative targets hiding in lipid pathways, ferroptosis, and the gut microbiome that could be used in addition to immuno-chemotherapy to improve the general health status of DLBCL patients, thus increasing the chance of being cured. It may be time to devote more effort to exploring DLBCL metabolism to discover novel druggable targets. We also performed a bibliometric and knowledge-map analysis of the literature on DLBCL published from 2014–2023.
Oxidized Low-Density Lipoprotein and Its Role in Immunometabolism
Authors: Mosalmanzadeh Negin , Pence Brandt D.
Published: October 2024

Modified cholesterols such as oxidized low-density lipoprotein (OxLDL) contribute to atherosclerosis and other disorders through the promotion of foam cell formation and inflammation. In recent years, it has become evident that immune cell responses to inflammatory molecules such as OxLDLs depend on cellular metabolic functions. This review examines the known effects of OxLDL on immunometabolism and immune cell responses in atherosclerosis and several other diseases. We additionally provide context on the relationship between OxLDL and aging/senescence and identify gaps in the literature and our current understanding in these areas.
Mycelium-Doped Straw Biochars for Antibiotic Control
Authors: Zhang Bolun , Li Ruqi , Zhang Huiji , Han Ye , Jia Yunzhe , Chen Siji , Yu Xiaoxiao
Published: October 2024

Straw, a predominant agricultural residue, represents a significant waste product. Harnessing its potential is of paramount importance both in terms of research and economic value. In this study, chemically pretreated corn straw was infused with distinct microbial fungal mycelium variants and subsequently transformed into a series of biochars through a process involving carbonization and activation. The findings revealed enhancements in the specific surface area and total pore volume of mycelium-doped straw biochars compared to the original corn straw biochar (BCS). Additionally, discernible disparities were observed in their physical and chemical attributes, encompassing functional groups, surface chemistry, and micro-morphology. Notably, in water-based antibiotic removal experiments focusing on tetracycline hydrochloride (TH) and chloramphenicol (CP), the mycelium-doped straw biochars outperformed BCS. Their maximum adsorption capacities for TH and CP surpassed those of alternative adsorbents, including other biochars. Impressively, even after five cycles, the biochar exhibited a removal rate exceeding 80%, attesting to its robust stability. This study successfully emphasized the efficacy of incorporating fungal mycelium to enhance the adsorption properties of straw-based biochar, introducing a new theoretical basis for the development of lignocellulosic materials.
Exploring the Potential of Fungal Biomass for Bisphenol A Removal in Aquatic Environments
Authors: Wlizło Kamila , Siwulski Marek , Kowalska-Krochmal Beata , Wiater Adrian
Published: October 2024

Bisphenol A is a plastic component, which shows endocrine activity that is detrimental to humans and aquatic ecosystems. The elimination of BPA from the environment is one of the solutions for BPA contaminant management. Adsorption is a cost-effective, easy-to-use method generating low harmful byproducts; nevertheless, contaminant sorbent treatment is a challenge that still needs to be addressed. Fungal fruiting bodies biomass is rarely studied sorbent but is promising due to its high polysaccharide content and availability. Our preliminary studies showed BPA sorption (100 mg/L) by 50 cultivated and wild fungi. The cultivated species: Clitocybe maxima (82%), Pholiota nameko (77%), and Pleurotus columbinus (74%), and wild fungi Cantharellus cibarius (75%) and Lactarius deliciosus (72%) were the most efficient. The biomass was able to sorb BPA over a broad range of temperature and pH levels, with an optimum at 20 °C and pH 7. Although saturation of sorbents was rapid, the regeneration process using ethanol was effective and allowed to recover up to 75% of sorbents’ initial efficiency. A single use of 1 g of sorbent would allow the treatment of 8.86 to 10.1 m3 of wastewater effluent, 16.5 to 18.7 m3 of surface water, and 411 to 469 m3 of drinking water, assuming the concentrations of BPA reported in the literature.
Conformational Plasticity Enhances the Brain Penetration of a Metabolically Stable, Dual-Functional Opioid-Peptide CycloAnt
Authors: Li Yangmei , Cotham William E. , Eliasof Abbe , Bland Kathryn , Walla Michael , Pellechia Perry J. , Chen Chongguang , Fan Daping , McLaughlin Jay P. , Liu-Chen Lee-Yuan
Published: October 2024

CycloAnt is an opioid peptide that produces potent and efficacious antinociception with significantly reduced side effects upon systemic administration in mice. To verify its CNS-mediated antinociception, we determined its binding affinity at the opioid receptors, its proteolytic stability in mouse serum, metabolic stability in mouse liver microsomes, and pharmacokinetics in mice. CycloAnt exhibited stability toward proteolytic degradation in serum and resistance against metabolism mediated by cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyl transferases (UGTs) in mouse liver microsomes. A pharmacokinetic study of CycloAnt in mice confirmed that CycloAnt crossed the blood–brain barrier (BBB) with a brain-to-plasma ratio of 11.5%, a high extent of BBB transport for a peptide. To elucidate the structural basis underlying its BBB penetration, we investigated its conformation in water and DMSO using 1H NMR spectroscopy. The results show that CycloAnt displays an extended conformation in water with most amide NHs being exposed, while in less polar DMSO, it adopts a compact conformation with all amide NHs locked in intramolecular hydrogen bonds. The chameleonic property helps CycloAnt permeate the BBB.
Systematic Investigation on Acid-Catalyzed Truncation of N-Acylated Peptoids
Authors: Piao Ruiqi , Kwon Yong-Uk
Published: October 2024

Peptoids have emerged as a useful alternative to peptides. However, N-acylated peptoids have occasionally undergone truncation at the terminal peptoid unit under acidic conditions. We previously reported on the mechanistic and electronic aspects of the acid-catalyzed truncation of N-acylated peptoids. To gain further insight, we systematically investigated the conformational and electronic effects of the terminal side chains of peptoids. The n→π* interaction, based on cis/trans-amide bond conformation, is considered to be one of the determining factors. In this study, it was demonstrated that both conformational and electronic factors contribute to this unusual truncation.
Pharmacological Preconditioning with Fenofibrate in Cardiomyocyte Cultures of Neonatal Rats Subjected to Hypoxia/Reoxygenation, High Glucose, and Their Combination
Authors: Oidor-Chan Víctor Hugo , Sánchez-López Araceli , Cano-Martinez Agustina , García-Niño Willy Ramses , Soria-Castro Elizabeth , del Valle-Mondragón Leonardo , Zarco-Olvera Gabriela , Patlán Mariana , Guarner-Lans Veronica , Rodríguez-Maldonado Emma , Flores-Estrada Javier , Castrejón-Téllez Vicente , Ibarra-Lara Luz
Published: October 2024

Pharmacological preconditioning is an alternative to protect the heart against the consequences of damage from ischemia/reperfusion (I/R). It is based on the administration of specific drugs that imitate the effect of ischemic preconditioning (IPC). Peroxisomal proliferator-activated receptors (PPARs) can prevent apoptosis in pathologies such as I/R and heart failure. Therefore, our objective was to determine if the stimulation of PPARα with fenofibrate (feno) decreases the apoptotic process induced by hypoxia/reoxygenation (HR), high glucose (HG), and HR/HG. For that purpose, cardiomyocyte cultures were divided into the following groups: Group 1—control (Ctrl); Group 2—HR; Group 3—HR + 10 μM feno; Group 4—HG, (25 mM glucose); Group 5—HG + feno; Group 6—HR/HG, and Group 7—HR/HG + feno. Our results indicate that cell viability decreases in neonatal cardiomyocytes undergoing HR, HG, and their combination, while feno improved cell viability. Feno treatment decreased apoptosis compared with HG-, HR-, or HG/HR-vehicle-treated. Nuclear- and mitochondrial-apoptosis markers increased in neonatal cardiomyocytes from HR, HG, and HR/HG; while the cytotoxicity decreased in cells treated with feno. In addition, the expression of Bax, Bad, and caspase 9 decreased due to feno, while 14-3-3ɛ and Bcl2 were increased. Inner mitochondrial cytochrome C increased with feno in every condition, as well as mitochondrial activity. Feno treatment prevented injury in the ultrastructure and in the mitochondrial membranes. Thus, our results suggest that feno decreases apoptosis in neonatal cardiomyocytes, improving the ultrastructure of mitochondria in the pathological conditions studied.
IL-1 Blockade Mitigates Autism and Cerebral Palsy Traits in Offspring In-Utero Exposed to Group B Streptococcus Chorioamnionitis
Authors: Ayash Taghreed A. , Allard Marie-Julie , Chevin Mathilde , Sébire Guillaume
Published: October 2024

Group B Streptococcus (GBS) is one of the most common bacteria responsible for placental and neonatal infection and inflammation resulting in lifelong neurobehavioral impairments. In particular, GBS-induced chorioamnionitis is known in preclinical models to upregulate inflammatory pathways, primarily through the activation of the interleukin-1 (IL-1) pathway, leading to brain injury and subsequent neurodevelopmental issues. Previous studies from our laboratory using Lewis rat pups have shown that male offspring exposed in utero to GBS chorioamnionitis develop brain injuries leading to neurobehavioral impairments such as autistic traits. In the present study, we aimed to explore whether blocking the IL-1 pathway could prevent or mitigate these neurodevelopmental impairments in adulthood. Using our established preclinical model, we administered IL-1 receptor antagonist (IL-1Ra) to dams with GBS-induced chorioamnionitis. Here, we show that IL-1Ra administration to dams reversed autistic and cerebral palsy traits in male adult offspring exposed in utero to GBS. Hence, IL-1 blockade could serve as a therapeutic intervention against pathogen-induced neurodevelopmental disorders. This research supports the need for future human randomized controlled trials to assess IL-1 blockade administered during pregnancy or in newborns as a strategy to reduce the long-term neurobehavioral consequences of prenatal infections, such as autism, cerebral palsy, learning disabilities, and other neurodevelopmental disorders.
Interaction Between Peroxisome Proliferator-Activated Receptors and Cannabidiol in the Gut of Chickens Applied to Different Challenge Conditions
Authors: Szkopek Dominika , Mendel Marta , Kinsner Misza , Fotschki Bartosz , Juśkiewicz Jerzy , Kozłowski Krzysztof , Matusevičius Paulius , Konieczka Paweł
Published: October 2024

Peroxisome proliferator-activated receptors (PPARs) are important targets for cannabidiol (CBD), which mediate many of its biological actions. The hypothesis of the present research assumed that PPARs affect the gut response to different challenge factors in chickens (C. perfringens vs. lipopolysaccharides (LPS) from E. coli), and that CBD can mediate the pathways of this response. The study proved that CBD and the challenge factors significantly affect the expression level of PPARα (p = 0.001) and selected genes determining gut barrier function. A positive correlation was demonstrated between PPARs and genes involved in the formation of tight junctions, immune, and oxidative stress responses in chickens. Dietary supplementation with CBD actively mediated the expression rate of PPARs, but the mechanism of interaction between CBD and PPARs was different depending on the stress factor used. The addition of CBD to the birds’ diets did not contribute to reducing intestinal permeability under induced stress conditions nor cause stress, as indicated by the absence of elevated blood cortisol and endotoxin levels. CBD also supported the mechanisms of protecting intestinal cells from the cytotoxic effects in a C. perfringens challenge through the levels of genes involved in oxidative stress. This study indicates the importance of research toward understanding the mechanisms of PPARs as a target for enhancing intestinal barrier function, provides new results on the biological action of CBD in chickens, and shows a constant PPAR association with the jejunum mucosa of birds.
Noradrenaline Protects Human Microglial Cells (HMC3) Against Apoptosis and DNA Damage Induced by LPS and Aβ1-42 Aggregates In Vitro
Authors: Barczuk Julia , Galita Grzegorz , Siwecka Natalia , Golberg Michał , Saramowicz Kamil , Granek Zuzanna , Wiese Wojciech , Majsterek Ireneusz , Rozpędek-Kamińska Wioletta
Published: October 2024

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. This study investigates the protective effects of noradrenaline (NA) on human microglial cells exposed to lipopolysaccharides (LPS) and Aβ aggregates—major contributors to inflammation and cellular damage in AD. The reduced Aβ aggregation in the HMC3 human microglial cells co-treated with Aβ and NA was confirmed by thioflavin T (ThT) assay, fluorescent ThT staining, and immunocytochemistry (ICC). The significantly increased viability of HMC3 cells after 48 h of incubation with NA at 50 µM, 25 µM, and 10 µM, exposed to IC50 LPS and IC50 Aβ, was confirmed by XTT and LDH assays. Moreover, we found that NA treatment at 25 μM and 50 μM concentrations in HMC3 cells exposed to IC50 LPS or IC50 Aβ results in an increased proliferation of HMC3 cells, their return to normal morphology, decreased levels of DNA damage, reduced caspase-3 activity, decreased expression of pro-apoptotic DDIT3 and BAX, and increased expression of anti-apoptotic BCL-2 genes and proteins, leading to enhanced cell survival, when compared to that of the HMC3 cells treated only with IC50 LPS or IC50 Aβ. Furthermore, we showed that NA induces the degradation of both extracellular and intracellular Aβ deposits and downregulates hypoxia-inducible factor 1α (HIF-1α), which is linked to impaired Aβ clearance and AD progression. These findings indicate that NA holds promise as a therapeutic target to address microglial dysfunction and potentially slow the progression of AD. Its neuroprotective effects, particularly in reducing inflammation and regulating microglial activity, warrant further investigation into its broader role in mitigating neuroinflammation and preserving microglial function in AD.