bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Carbon-Reduction-Oriented Demand Response Technology Based on Generalized Nodal Carbon Emission Flow Theory
Authors: Zhang Shixu , Li Yaowang , Du Ershun , Wang Wei , Wang Min , Feng Haoran , Xie Yi , Chen Qiuyu
Published: September 2024

The decarbonization of power systems plays a great part in the carbon neutrality goal. Currently, researchers have explored reducing carbon in power systems in terms of the optimization of energy supply structure and operation strategies, but ignored the carbon reduction potential of users. To investigate the carbon reduction capability of users and further promote power system decarbonization through the active response of electricity loads, this paper proposes a carbon-reduction-oriented demand response (CRODR) technology based on generalized nodal carbon emission flow theory. First, the framework of the CRODR mechanism is established to provide an interaction baseline for users facing carbon reduction guiding signals. Secondly, the generalized nodal carbon emission flow theory is introduced to provide a calculation method for the guiding signals, considering dynamic electricity carbon emission factors with various spatiotemporal resolutions. Then, a matrix-based method is proposed to efficiently solve the carbon emission flow and obtain the guiding signals. On this basis, an optimal load-regulating model to help users meet their carbon reduction goals is built, and a carbon reduction benefit-evaluation method is proposed. Case studies on China’s national power system and a textile company verify that CRODR technology can realize efficient carbon reduction through load shifting while maintaining the total power consumption of users. The proposed CRODR technology is expected to provide a theoretical basis and guiding mechanism for promoting carbon reduction throughout the entire power system.
Dynamic Failure Mode Analysis for a Transmission Tower-Line System Induced by Strong Winds
Authors: Liu Shizeng , Zhang Wentong , Li Qiang , Yan Shicheng , Zhang Shihong , Li Chao , Li Lixiao
Published: September 2024

The prevailing approach to the wind resistance design of transmission towers is rooted in the quasi-static method. However, this methodology faces criticism for neglecting tower-line coupling dynamics. Despite efforts to boost structural wind resilience, the research on tower failure mechanisms, especially under extreme winds considering tower-line coupling, is limited. To address this gap, the wind-induced dynamic failure modes of the transmission tower-line system are investigated in this paper. The consistent discrete random flow generation method is employed to simulate the fluctuating wind field for transmission lines. Incorporating the compressive buckling mode of angle steel, the plastic hinge model of the frame element is employed to simulate mechanical nonlinearity. A typical transmission tower-line system is concerned, with a finite element model established for a three-tower, four-line coupled configuration. The findings reveal that the wind-induced collapse of the transmission tower is directly triggered by the buckling failure of the compressed main members, with the vulnerable section located beneath the lower cross-arm. The transmission tower experiences bidirectional bending and compression instability under an unfavorable wind direction. In contrast, the traditional pushover collapse modes of the transmission tower cannot fully capture the characteristics of the collapse failure, mainly due to the ignorance of the transverse wind force action induced by the coupling effect. This research underscores the importance of incorporating lateral dynamic considerations into transmission tower designs and advocates for optimizing strategies to mitigate wind-induced collapse modes.
Analysis of Demand Response in Electric Systems with Strong Presence of Intermittent Generation Using Conditional Value-at-Risk
Authors: Souza Rafael V. X. de , Sousa Thales
Published: September 2024

The integration of renewable sources, such as hydro, wind, and solar power, into electrical systems has profoundly transformed the sector’s dynamics. The inherent intermittency of these energy sources, due to the uncertainty associated with inflows, winds, and solar irradiation, introduces considerable challenges in the operation and planning of the electrical system. In this context, demand response emerges as a promising solution to handle the fluctuations in renewable generation and maintain system stability and reliability. Therefore, this study presents a new approach to the demand response program through the modeling of an optimal power flow problem to minimize operational costs, considering the uncertainties in hydro, wind, and solar generation by applying the Conditional Value-at-Risk (CVaR) risk metric. The mathematical modeling of the problem was conducted, and the problem was solved using the MINOS solver. To validate the model, simulations were carried out using modified IEEE systems of 14, 30, 57, and 118 buses, considering operation planning for the next 24 h. Furthermore, sensitivity analyses were performed by altering the CVaR parameters. As a result of the simulations, the total operational cost, electrical losses, and hourly generation at each bus by source type were determined, highlighting how CVaR impacts the operation of this type of system.
Numerical Analysis of Leakage and Diffusion Characteristics of In-Situ Coal Gas with Complex Components
Authors: Liu Enbin , Zhou Lianle , Tang Ping , Kou Bo , Li Xi , Lu Xudong
Published: September 2024

To alleviate the shortage of natural gas supply, the in-situ conversion of coal to natural gas is more beneficial for advancing the clean and efficient use of energy. Since in-situ coal gas contains complex components, such as H2, CH4, and CO, their leakage poses a serious risk to human life and property. Currently, the area of consequence of the harm caused by a leak in a gathering pipeline transporting in-situ coal gas has not been clarified. Therefore, this paper adopted the method of numerical simulation to pre-study the concentration distribution of each component and determined that the main components of concern are CO and H2 components. Afterward, the diffusion law of in-situ coal gas is analyzed and studied under different working conditions, such as wind speed, temperature, pipe diameter, leakage direction, and leakage aperture ratio. The results indicate that when a pipeline leak occurs, the CO component has the largest influence range. With increasing wind speed, the warning boundary of CO rapidly expands downwind, then gradually diminishes, reaching a peak value of 231.62 m at 7 m/s. The range of influence of the leaked gas is inversely proportional to temperature and directly proportional to pipe diameter and leakage aperture ratio. When the gas leaks laterally, the diffusion early warning boundary value of each component is maximal. Among them, the leakage aperture ratio has a significant impact on the concentration distribution of in-situ coal gas, whereas the effect of temperature is relatively minor. This study contributes to an understanding of the leakage and diffusion characteristics of in-situ coal gas-gathering pipelines.
Determinants to Adopt Industrial Internet of Things in Small and Medium-Sized Enterprises
Authors: Khanfor Abdullah
Published: September 2024

The Industrial Internet of Things (IIoT) enhances and optimizes operations and product quality by reducing expenses and preserving critical factory components. The IIoT can also be integrated into the processes of small and medium-sized enterprises (SMEs). However, several factors and risks have discouraged SMEs from adopting the IIoT. This study aims to identify the factors influencing IIoT adoption and address the challenges by conducting semi-structured interviews with experienced stakeholders in SME factories. Group quotations and thematic analysis indicate essential themes from these interviews, suggesting two primary categories, human- and machine-related factors, that affect implementation. The main human-related factor is the decision making of high-level management and owners to implement the IIoT in their plants, which requires skilled individuals to achieve IIoT solutions. Machine-related factors present several challenges, including device compatibility-, device management-, and data storage-associated issues. Comprehending and addressing these factors when deploying the IIoT can ensure successful implementation in SMEs, maximizing the potential benefits of this technology.
Decentralized Mechanism for Edge Node Allocation in Access Network: An Experimental Evaluation
Authors: Calle-Cancho Jesus , Cañada Carlos , Pastor-Vargas Rafael , Paoletti Mercedes E. , Haut Juan M.
Published: September 2024

With the rapid advancement of the Internet of Things and the emergence of 6G networks in smart city environments, a growth in the generation of data, commonly known as big data, is expected to consequently lead to higher latency. To mitigate this latency, mobile edge computing has been proposed to alleviate a portion of the workload from mobile devices by offloading it to nearby edge servers equipped with appropriate computational resources. However, existing solutions often exhibit poor performance when confronted with complex network topologies. Thus, this paper introduces a decentralized mechanism aimed at determining the locations of network edge nodes in such complex network topologies, characterized by lengthy execution times. Our proposal provides performance improvements and offers scalability and flexibility as networks become more complex. Experimental evaluations are conducted using the Shanghai Telecom dataset to validate our proposed approach.
Artificial Intelligence to Reshape the Healthcare Ecosystem
Authors: Reali Gianluca , Femminella Mauro
Published: September 2024

This paper intends to provide the reader with an overview of the main processes that are introducing artificial intelligence (AI) into healthcare services. The first part is organized according to an evolutionary perspective. We first describe the role that digital technologies have had in shaping the current healthcare methodologies and the relevant foundations for new evolutionary scenarios. Subsequently, the various evolutionary paths are illustrated with reference to AI techniques and their research activities, specifying their degree of readiness for actual clinical use. The organization of this paper is based on the interplay three pillars, namely, algorithms, enabling technologies and regulations, and healthcare methodologies. Through this organization we introduce the reader to the main evolutionary aspects of the healthcare ecosystem, to associate clinical needs with appropriate methodologies. We also explore the different aspects related to the Internet of the future that are not typically presented in papers that focus on AI, but that are equally crucial to determine the success of current research and development activities in healthcare.
Fundamentals of Edible Coatings and Combination with Biocontrol Agents: A Strategy to Improve Postharvest Fruit Preservation
Authors: Miranda Marcela , Bai Jinhe , Pilon Lucimeire , Torres Rosario , Casals Carla , Solsona Cristina , Teixidó Neus
Published: September 2024

Challenges in global food supply chains include preserving postharvest quality and extending the shelf life of fruits and vegetables. The utilization of edible coatings (ECs) combined with biocontrol agents (BCAs) represents a promising strategy to enhance the postharvest quality and shelf life of these commodities. This review analyzes the most recent developments in EC technologies and their combination with BCAs, highlighting their synergistic effects on postharvest pathogen control and quality maintenance. Various types of ECs, including polysaccharides, proteins, and lipids, are discussed alongside coating fundamentals and the mechanisms through which BCAs contribute to pathogen suppression. The review also highlights the efficacy of these combined approaches in maintaining the physicochemical properties, sensory attributes, and nutritional value of fruits. Key challenges such as regulatory requirements, consumer acceptance, and the scalability of these technologies are addressed. Future research directions are proposed to optimize formulations, improve application techniques, and enhance the overall efficacy of these biocomposite coatings and multifunctional coatings. By synthesizing current knowledge and identifying gaps, this review provides a comprehensive understanding of the potential and limitations of using ECs and BCAs for sustainable postharvest management.
Antioxidant and Biological Activity of Mexican Madroño Fruit (Arbutus arizonica)
Authors: Monroy-García Imelda N. , Carranza-Rosales Pilar , Carranza-Torres Irma Edith , Castro-Ochoa Lelie Denisse , González-Villasana Vianey , Islas-Rubio Alma Rosa , Viveros-Valdez Ezequiel
Published: September 2024

The fruit of the Mexican madroño (Arbutus arizonica) has been consumed since pre-Columbian times by North American tribes and native groups in Mexico. Despite this, reports on its chemical composition and biological activity are limited. This work aims to determine the antioxidant, antiproliferative, and digestive enzyme inhibition activities of the methanol amberlite-retained extract of Mexican madroño. Results showed that madroño fruit is rich in antioxidants: DPPH (EC50 = 0.89 ± 0.03 mg/mL), TEAC (1078 ± 4.9 μM/g), and hemolysis inhibition (IC50 = 358.07 μg/mL), with high phenolic and flavonoid content at 15.92 ± 3.2 mg GAE/g and 4.33 ± 0.3 mg CA/g, respectively. Using analytical chromatography, gallic acid, vanillic acid, chlorogenic acid, ferulic acid, quercetin, and rutin were quantified. The extract also showed α-glucosidase inhibition (IC50 = 3.1 ± 0.17 mg/mL), but no inhibition against α-amylase and lipase (>5 mg/mL), while showing antiproliferative activity against HeLa, HT-29, and MCF-7 cancer cell lines. These results point towards an interesting potential for the fruit of the A. arizonica as chemopreventive and hold potential for elaborating functional foods.
Dellaglioa Algida Cell-Free Supernatant Inhibits Pseudomonas Fluorescence and Pseudomonas Fragi by Destroying Cell Membranes
Authors: Sun Yao , Wei Tianhui , Ma Tongqing , Fan Zhiying , Song Jinzhu
Published: September 2024

The aim of this study was to examine the components of the cell-free supernatant (CFS) derived from a novel strain of psychrophilic Lactobacillus, Dellaglioa algida, and to further elucidate the impact of this CFS on various cellular processes. Specifically, we sought to understand its effects on the cell membrane, protein and DNA release, protease activity, and metabolites of Pseudomonas fluorescens and Pseudomonas fragi, thereby clarifying the antibacterial mechanism involved. The CFS components were analyzed using Gas Chromatography–Mass Spectrometry (GC-MS), the Coomassie Brilliant Blue method, and the phenol–sulfuric acid method. The inhibitory effect of the CFS on Pseudomonas fluorescens and Pseudomonas fragi was assessed using the ethidium bromide (EB) assay, Oxford cup assay, and ultramicroassay. Additionally, we analyzed the metabolites produced by Pseudomonas fluorescens and Pseudomonas fragi when treated with the CFS. The findings reveal that the CFS of Dellaglioa algida contains 94 volatile components, with protein and sugar concentrations of 32.857 ± 0.9705 mg/mL and 98.250 ± 4.210 mg/L, respectively. The CFS induces varying degrees of damage to the cell membranes of both Pseudomonas fluorescens and Pseudomonas fragi, leading to the release of intracellular proteins and DNA. Furthermore, the CFS reduced the protease activity and metabolic capacity of Pseudomonas fluorescens and Pseudomonas fragi. These results enhance our understanding of the mechanism by which psychrophilic Dellaglioa algida inhibits Pseudomonas fluorescens and Pseudomonas fragi, confirming that its inhibitory effect predominantly occurs through damage to the biological cell membranes of Pseudomonas. Dellaglioa algida is a newly identified cold-adapted inhibitor of Pseudomonas, indicating that its CFS is an effective microbial inhibitor in cold environments. This discovery suggests potential applications in inhibiting the growth and reproduction of Pseudomonas fluorescens and Pseudomonas fragi in food, pharmaceuticals, perfumes, and other chemicals, providing a valuable new reference for industrial preservation.
The Influence of Different Hydrothermal Processes Used in the Preparation of Brussels Sprouts on the Availability of Glucosinolates to Humans
Authors: Sadowska-Rociek Anna , Doniec Joanna , Kusznierewicz Barbara , Dera Tomasz , Filipiak-Florkiewicz Agnieszka , Florkiewicz Adam
Published: September 2024

Cruciferous vegetables represent a valuable source of bioactive compounds. However, there is currently a deficiency of information regarding the extent to which these compounds remain bioaccessible to the body following thermal treatment and digestion processes within the digestive tract. Accordingly, the aim of this study was to evaluate the impact of heat treatment and in vitro digestion on the level of selected bioactive compounds in Brussels sprouts. The Brussels sprouts samples were subjected to a range of thermal processing techniques, which were then followed by a simulated in vitro digestion. The investigated compounds were analyzed using UV-Vis spectrometry and liquid chromatography coupled with mass spectrometry (LC-MS). The findings revealed that the sous-vide method of cooking Brussels sprouts resulted in significantly higher losses of glucosinolates (GLS) in comparison to conventional cooking methods. No significant differences were observed with regard to isothiocyanates and indoles. The analysis of GLS following digestion revealed that the process was more effective after sous vide and traditional cooking, and slightly less effective after steam cooking. With regard to individual compounds, glucoraphanin (GRA), glucoraphenin (GIV), and gluconasturtiin (GNS) were found to be completely degraded, whereas methoxyglucobrassicin (metGBS) was the most resistant to digestion in both the sous vide and steamed Brussels sprouts. The results indicated that the process of simulating digestion had no significant impact on isothiocyanates and indoles. This suggests that, if present in the heat-treated samples, these compounds remained stable during the in vitro digestion procedure.
The Role of Single Nucleotide Polymorphisms in MicroRNA Genes in Head and Neck Squamous Cell Carcinomas: Susceptibility and Prognosis
Authors: Szmida Elżbieta , Butkiewicz Dorota , Karpiński Paweł , Rutkowski Tomasz , Oczko-Wojciechowska Małgorzata , Sąsiadek Maria Małgorzata
Published: September 2024

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. MicroRNAs (miRNAs), which belong to the group of important post-transcriptional regulators of human gene expression, seem to be valuable options for consideration as key modifiers of individual cancer risk, and therefore may be helpful in predicting inter-individual differences in cancer risk, response to treatment and prognosis. Methods: There have not been many studies focused on the relationship between miRNA variants and HNSCC published in PubMed within the last 15 years. We found and analyzed 30 reviews, meta-analyses and research papers and revealed 14 SNPs which have been reported as significant in the context of HNSCC susceptibility and/or prognosis. Results: These 14 SNPs were located in 13 separate miRNAs. Among them, four were the most frequently studied (miRNA-146, -196, -149 and -499) and have been shown to have the greatest impact on the course of HNSCC. However, the presented results have been conflicting. Conclusions: It must be concluded that, despite the years of studies, there are no conclusive reports demonstrating a significant role of SNPs in miRNAs in the context of the susceptibility to HNSCC or its prognosis.
Hepatic Transcriptome Reveals Potential Key Genes Contributing to Differential Milk Production
Authors: Du Chao , Zhu La A La Teng , Gao Shengtao , Gao Wenshuo , Ma Lu , Bu Dengpan , Zhang Wenju
Published: September 2024

Background: Despite the widespread adoption of TMR or PMR and the formulas designed to sufficiently cover the cows’ requirements, individual dairy cows’ milk production varies significantly. The liver is one of the most important organs in cow lactation metabolism and plays an essential role in the initiation of lactation. Objectives: This study aimed to investigate the potential key genes in the liver contributing to the different milk production. Methods: We enrolled 64 cows and assigned them to high or low milk yield (MY) groups according to their first 3 weeks of milk production. We performed RNAseq for 35 liver samples with 18 from prepartum and 17 from postpartum cows. Results: The continuous milk yield observation showed a persistently higher milk yield in high MY cows than low MY cows in the first 3 weeks. High MY cows showed better feed conversion efficiency. We identified 795 differentially expressed genes (DGEs) in the liver of high MY cows compared with low MY cows, with up-regulated genes linked to morphogenesis and development pathways. Weighted gene co-expression network analysis (WGCNA) revealed four gene modules positively correlating with milk yield, and protein and lactose yield (p < 0.05). Using the intersected genes between the four gene modules and DEGs, we constructed the linear mixed-effects models and identified six hub genes positively associated and two hub genes negatively associated with milk yield (Coefficients > 0.25, p < 0.05). Random forest machine learning model training based on these eight hub genes could efficiently predict the milk yield (p < 0.001, R2 = 0.946). Interestingly, the expression patterns of these eight hub genes remained remarkably similar before and after parturition. Conclusions: The present study indicated the critical role of liver in milk production. Activated processes involved in morphogenesis and development in liver may contribute to the higher milk production. Eight hub genes identified in this study may provide genetic research materials for dairy cow breeding.
The Mediating Roles of Lung Function Traits and Inflammatory Factors on the Associations between Measures of Obesity and Risk of Lower Respiratory Tract Infections: A Mendelian Randomization Study
Authors: Ma Xiaofeng , Zhu Pan-Pan , Yang Qian , Sun Yangbo , Ou Chun-Quan , Li Li
Published: September 2024

Background: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. Methods: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. Results: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. Conclusions: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs.
Effective Nature-Based Outdoor Play and Learning Environments for below-3 Children: A Literature-Based Summary
Authors: Craig Danielle , Trina Nazia Afrin , Monsur Muntazar , Haque Umme Tasnima , Farrow Garrett , Hasan Md Zahid , Tasnim Fariha , Akinbobola Moyin Sabainah
Published: September 2024

Early childhood (0–8 years) is a time of rapid brain development supported by spontaneous and informal learning from the surrounding environment. Meaningful contact with nature (a dynamic and varied source of informal learning) during the early years of life sets up rich scopes for such spontaneous learning—especially in the first three years, a period in life that determines all future learning, behavior, and health. Besides its learning affordances, nature-based environments provide numerous health and developmental benefits. Considering that more than 13 million children under 5 years of age in the US spend most of their waking hours in care facilities, the potential benefits of having a nature-based outdoor area in their primary care environments are immense. However, guidelines and assessment standards for designing nature-based outdoor environments for below-three children (infants and toddlers) are almost non-existent. This three-phase research holds the promise of addressing this issue. Phase 1 reviews the available limited literature on below-three children’s outdoor play and learning environments and summarizes their design implications. Phase 2 extracts effective design guidelines and identifies assessment indicators from the Phase 1 studies. In Phase 3, empirical data (environmental assessment data) are collected to compare the existing and proposed design environment conditions of below-3 outdoor play and learning environments in a selected childcare facility. This phase highlights evidence-based assumptions of new criteria, guidelines, and indicators to assess any below-3 nature-based childcare outdoor environments. This research provides new information and insights for designing nature-based outdoor play and learning environments for below-3 children to increase their meaningful connections with natural elements while attending a care facility.
Application of Exogenous Ascorbic Acid Enhances Cold Tolerance in Tomato Seedlings through Molecular and Physiological Responses
Authors: Wang Xinman , Ran Chunxia , Fu Yuandi , Han Liyuan , Yang Xuedong , Zhu Weimin , Zhang Hui , Zhang Yingying
Published: September 2024

Ascorbic acid (AsA), an essential non-enzymatic antioxidant in plants, regulates development growth and responses to abiotic and biotic stresses. However, research on AsA’s role in cold tolerance remains largely unknown. Here, our study uncovered the positive role of AsA in improving cold stress tolerance in tomato seedlings. Physiological analysis showed that AsA significantly enhanced the enzyme activity of the antioxidant defense system in tomato seedling leaves and increased the contents of proline, sugar, abscisic acid (ABA), and endogenous AsA. In addition, we found that AsA is able to protect the photosynthetic system of tomato seedlings, thereby relieving the declining rate of chlorophyll fluorescence parameters. qRT-PCR analysis indicated that AsA significantly increased the expression of genes encoding antioxidant enzymes and involved in AsA synthesis, ABA biosynthesis/signal transduction, and low-temperature responses in tomato. In conclusion, the application of exogenous AsA enhances cold stress tolerance in tomato seedlings through various molecular and physiological responses. This provides a theoretical foundation for exploring the regulatory mechanisms underlying cold tolerance in tomato and offers practical guidance for enhancing cold tolerance in tomato cultivation.
Influence of Anticoagulants and Heparin Contaminants on the Suitability of MMP-9 as a Blood-Derived Biomarker
Authors: Küper Daniela , Klos Josefin , Kühl Friederike , Attili Rozan , Brand Korbinian , Weissenborn Karin , Lichtinghagen Ralf , Huber René
Published: September 2024

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9.
RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages
Authors: Yamashita Atsushi , Ito Yoshiya , Osada Mayuko , Matsuda Hiromi , Hosono Kanako , Tsujikawa Kazutake , Okamoto Hirotsugu , Amano Hideki
Published: September 2024

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that induces cytokine hypersecretion. Receptor activity-modifying protein (RAMP) 1, a subunit of the calcitonin gene-related peptide (CGRP) receptor, regulates the production of cytokines. This study examined the role of RAMP1 signaling during lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS administration to wild-type (WT) mice depleted alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) and neutrophils. RAMP1-deficient (RAMP1−/−) mice exhibited higher lung injury scores, cytokine levels, and cytokine-producing neutrophil infiltration. RAMP1-deficient AMs produced more cytokines in response to LPS than WT AMs. Adoptive transfer of RAMP1-deficient AMs to RAMP1−/− mice increased cytokine levels and neutrophil accumulation compared to the transfer of WT AMs. RAMP1−/− mice had reduced MDM recruitment and lower pro-inflammatory and reparative macrophage profiles. Cultured bone marrow (BM)-derived RAMP1-deficient macrophages stimulated with LPS showed decreased expression of pro-inflammatory and pro-repairing genes. CGRP administration to WT mice reduced cytokine production and neutrophil accumulation. These findings indicate that RAMP1 signaling mitigates LPS-induced ALI by inactivating AMs and promoting inflammatory and repair activities of MDMs. Targeting RAMP1 signaling presents a potential therapeutic approach for the treatment of ARDS.
NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor
Authors: Naamneh Elzenaty Rawda , Kouri Chrysanthi , Martinez de Lapiscina Idoia , Sauter Kay-Sara , Moreno Francisca , Camats-Tarruella Núria , Flück Christa E.
Published: September 2024

Steroidogenic factor 1 (SF-1) is a nuclear receptor that regulates steroidogenesis and reproductive development. NR5A1/SF-1 variants are associated with a broad spectrum of phenotypes across individuals with disorders of sex development (DSDs). Oligogenic inheritance has been suggested as an explanation. SF-1 interacts with numerous partners. Here, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual carrying an ACMG-categorized ‘pathogenic’ NR5A1/SF-1 variant in comparison to the healthy carrier father. Candidate genes were revealed by whole exome sequencing, and pathogenicity was predicted by different in silico tools. We found variants in NR1H2 and INHA associated with steroidogenesis, sex development, and reproduction. The identified variants were tested in cell models. Novel SF-1 and NR1H2 binding sites in the AR and INHA gene promoters were found. Transactivation studies showed that wild-type NR5A1/SF-1 regulates INHA and AR gene expression, while the NR5A1/SF-1 variant had decreased transcriptional activity. NR1H2 was found to regulate AR gene transcription; however, the NR1H2 variant showed normal activity. This study expands the NR5A1/SF-1 network of interacting partners, while not solving the exact interplay of different variants that might be involved in revealing the observed DSD phenotype. It also illustrates that understanding complex genetics in DSDs is challenging.
Nebulized Lipopolysaccharide Causes Delayed Cortical Neuroinflammation in a Murine Model of Acute Lung Injury
Authors: Ritter Katharina , Rissel René , Renz Miriam , Ziebart Alexander , Schäfer Michael K. E. , Kamuf Jens
Published: September 2024

Lung injury caused by respiratory infection is a major cause of hospitalization and mortality and a leading origin of sepsis. Sepsis-associated encephalopathy and delirium are frequent complications in patients with severe lung injury, yet the pathogenetic mechanisms remain unclear. Here, 70 female C57BL/6 mice were subjected to a single full-body-exposure with nebulized lipopolysaccharide (LPS). Neuromotor impairment was assessed repeatedly and brain, blood, and lung samples were analyzed at survival points of 24 h, 48 h, 72 h, and 96 h after exposure. qRT-PCR revealed increased mRNA-expression of TNFα and IL-1β 24 h and 48 h after LPS-exposure in the lung, concomitantly with increased amounts of proteins in bronchoalveolar lavage and interstitial lung edema. In the cerebral cortex, at 72 h and/or 96 h after LPS exposure, the inflammation- and activity-associated markers TLR4, GFAP, Gadd45b, c-Fos, and Arc were increased. Therefore, single exposure to nebulized LPS not only triggers an early inflammatory reaction in the lung but also induces a delayed neuroinflammatory response. The identified mechanisms provide new insights into the pathogenesis of sepsis-associated encephalopathy and might serve as targets for future therapeutic approaches.
Tuberculous Pleural Effusion-Derived Exosomal miR-130b-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1
Authors: Kang Hyun-Jung , Yun Sangho , Shin Seung-Ho , Youn Dong Hyuk , Son Ga-Hyun , Lee Jae Jun , Hong Ji Young
Published: September 2024

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.
Immune Checkpoint Inhibitor Therapy for Metastatic Melanoma: What Should We Focus on to Improve the Clinical Outcomes?
Authors: Hossain Sultana Mehbuba , Ly Kevin , Sung Yih Jian , Braithwaite Antony , Li Kunyu
Published: September 2024

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enhancing anti-tumour immune responses, demonstrating significant efficacy in various malignancies, including melanoma. However, over 50% of patients experience limited or no response to ICI therapy. Resistance to ICIs is influenced by a complex interplay of tumour intrinsic and extrinsic factors. This review summarizes current ICIs for melanoma and the factors involved in resistance to the treatment. We also discuss emerging evidence that the microbiota can impact ICI treatment outcomes by modulating tumour biology and anti-tumour immune function. Furthermore, microbiota profiles may offer a non-invasive method for predicting ICI response. Therefore, future research into microbiota manipulation could provide cost-effective strategies to enhance ICI efficacy and improve outcomes for melanoma patients.
Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
Authors: Ferre-Giraldo Adriana , Castells Manel , Sánchez-Herrero José Francisco , López-Rodrigo Olga , de Rocco-Ponce Maurizio , Bassas Lluís , Vigués Francesc , Sumoy Lauro , Larriba Sara
Published: September 2024

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5′tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5′-tRNA-Glu-TTC-9-1_L30 and 5′-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5′tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5′tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.
Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation
Authors: Peters Kirsten , Staehlke Susanne , Rebl Henrike , Jonitz-Heincke Anika , Hahn Olga
Published: September 2024

Metals play a crucial role in the human body, especially as ions in metalloproteins. Essential metals, such as calcium, iron, and zinc are crucial for various physiological functions, but their interactions within biological networks are complex and not fully understood. Mesenchymal stem/stromal cells (MSCs) are essential for tissue regeneration due to their ability to differentiate into various cell types. This review article addresses the effects of physiological and unphysiological, but not directly toxic, metal ion concentrations, particularly concerning MSCs. Overloading or unbalancing of metal ion concentrations can significantly impair the function and differentiation capacity of MSCs. In addition, excessive or unbalanced metal ion concentrations can lead to oxidative stress, which can affect viability or inflammation. Data on the effects of metal ions on MSC differentiation are limited and often contradictory. Future research should, therefore, aim to clarify the mechanisms by which metal ions affect MSC differentiation, focusing on aspects such as metal ion interactions, ion concentrations, exposure duration, and other environmental conditions. Understanding these interactions could ultimately improve the design of biomaterials and implants to promote MSC-mediated tissue regeneration. It could also lead to the development of innovative therapeutic strategies in regenerative medicine.
Influence of the Chemical Properties of Cereal Grains on the Structure and Metabolism of the Bacteriome of Rhyzopertha dominica (F.) and Its Development: A Cause–Effect Analysis
Authors: Kosewska Olga , Przemieniecki Sebastian Wojciech , Nietupski Mariusz
Published: September 2024

Rhyzopertha dominica causes significant economic losses in stored cereals. Insects’ digestive tract microbiome is crucial for their development, metabolism, resistance, and digestion. This work aimed to test whether the different chemical properties of different wheat and barley grain cultivars cause disturbances in insect foraging and rearrangements of the structure of the R. dominica microbiome. The results indicated that grain cultivars significantly influence the microbiome, metabolism, and insect foraging. Most observed traits and microbiome structures were not correlated at the species level, as confirmed by ANOSIM (p = 0.441). However, the PLS-PM analysis revealed significant patterns within barley cultivars. The study found associations between C18:2 fatty acids, entomopathogenic bacteria, an impaired nitrogen cycle, lysine production of bacterial origin, and insect feeding. The antioxidant effects also showed trends towards impacting the microbiome and insect development. The findings suggest that manipulating grain chemical properties (increasing C18:2 and antioxidant levels) can influence the R. dominica microbiome, disrupting their foraging behaviours and adaptation to storage environments. This research supports the potential for breeding resistant cereals, offering an effective pest control strategy and reducing pesticide use in food production.
Ladybird Beetle Diversity in Natural and Human-Modified Habitats in the San Cristóbal Island, Galapagos, Ecuador
Authors: Peñaherrera-Romero Emilia , Guerrero-Campoverde Ariel , Rueda-Rodríguez María P. , Dávila-Játiva Mateo , Die-Morejón Daniel , Domínguez-Trujillo Mariela , Guerrero-Molina Tomás , Vélez-Darquea Emilio , Cisneros-Heredia Diego F.
Published: September 2024

This study investigates the species richness and distribution of ladybird beetles (Coccinellidae) across various habitats on San Cristóbal Island in the Galápagos Archipelago, Ecuador. Through extensive field surveys, we catalogued nineteen species, including four previously known species (two endemics, Psyllobora bisigma and Scymnobius scalesius, and two natives, Cycloneda sanguinea and Tenuisvalvae bromelicola). We also identified nine possibly native species reported for the first time in the Galapagos islands in this study or correspond to the first voucher specimens for the island. We collected three previously reported non-native species: Cheilomenes sexmaculata, Novius cardinalis, and Paraneda guticollis. Three species belonging to the genera Stethorus, Calloeneis, and Delphastus remain undetermined, pending further taxonomic analyses. Our findings reveal a rich and complex community with notable differences in species abundance and habitat preference. Endemic species were found to be particularly scarce and restricted mainly to crops undergoing forest regeneration and deciduous forests, emphasising their vulnerability and specialised habitat requirements. The native Cycloneda sanguinea emerged as the most prevalent species, exhibiting broad ecological adaptability. Non-native species, like Cheilomenes sexmaculata, were predominantly found in disturbed habitats, with some showing early signs of spreading into more natural environments, raising concerns about their potential impact on local biodiversity. These findings contribute valuable knowledge to understanding Coccinellidae diversity on San Cristóbal Island and highlight the importance of continued monitoring, particularly in the face of ongoing environmental change and the introduction of non-native species. This study underscores the need for targeted conservation efforts to protect the unique and fragile ecosystems of the Galápagos Archipelago.
Development and Initial Testing of an Artificial Intelligence-Based Virtual Reality Companion for People Living with Dementia in Long-Term Care
Authors: Sheehy Lisa , Bouchard Stéphane , Kakkar Anupriya , El Hakim Rama , Lhoest Justine , Frank Andrew
Published: September 2024

Background/Objectives: Feelings of loneliness are common in people living with dementia (PLWD) in long-term care (LTC). The goals of this study were to describe the development of a novel virtual companion for PLWD living in LTC and assess its feasibility and acceptability. Methods: The computer-generated virtual companion, presented using a head-mounted virtual reality display, was developed in two stages. In Stage 1, the virtual companion asked questions designed to encourage conversation and reminiscence. In Stage 2, more powerful artificial intelligence tools allowed the virtual companion to engage users in nuanced discussions on any topic. PLWD in LTC tested the application at each stage to assess feasibility and acceptability. Results: Ten PLWD living in LTC participated in Stage 1 (4 men and 6 women; average 82 years old) and Stage 2 (2 men and 8 women; average 87 years old). Session lengths ranged from 0:00 to 5:30 min in Stage 1 and 0:00 to 53:50 min in Stage 2. Speech recognition issues and a limited repertoire of questions limited acceptance in Stage 1. Enhanced conversational ability in Stage 2 led to intimate and meaningful conversations with many participants. Many users found the head-mounted display heavy. There were no complaints of simulator sickness. The virtual companion was best suited to PLWD who could engage in reciprocal conversation. After Stage 2, response latency was identified as an opportunity for improvement in future versions. Conclusions: Virtual reality and artificial intelligence can be used to create a virtual companion that is acceptable and enjoyable to some PLWD living in LTC. Ongoing innovations in hardware and software will allow future iterations to provide more natural conversational interaction and an enhanced social experience.