bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Loss Modeling for Multi-Stage Obstacles in Pressurized Ducts
Authors: Bon Guillaume , Chatellier Ludovic , Le Guer Yves , Bellot Cécile , Casiot Xavier , David Laurent
Published: July 2024

Estimating singular pressure losses for multi-stage obstacles in pressurized hydraulic ducts is a challenging task. An experimental study was conducted in a closed-loop hydrodynamic tunnel to characterize the pressure losses of a system consisting of a porous fibrous foam placed in front of a bar rack. The pressure losses of different foam–rack configurations were measured over a range of inlet velocities in order to highlight the mutual influence of their characteristics on the flow. The interdependence between the two stages has been evidenced by both the experimental results and additional numerical simulations using RANS (Reynolds-Averaged Navier–Stokes Equations) simulations with a k-ω SST turbulent closure model. The pressure losses were first modeled using two approaches based on the assumption of either independence or full dependence between the stages. The respective advantages and limitations of these approaches led to an improved analytical formula that considers the transition of the flow from the porous foam to the bar rack. By taking into account an empirical transition factor, the proposed model improves the head loss prediction for all tested configurations, with an average relative error between the formula and experimental results less than that of the two simpler approaches. This study improves our understanding of global pressure losses in multi-stage systems that include a porous foam or other filtering or clogging media in front of bar racks.
CH4 Adsorption in Wet Metal-Organic Frameworks under Gas Hydrate Formation Conditions Using A Large Reactor
Authors: Pandey Jyoti Shanker , Öncü Nehir , von Solms Nicolas
Published: July 2024

Nanoporous materials, such as metal-organic frameworks (MOFs), are renowned for their high selectivity as gas adsorbents due to their specific surface area, nanoporosity, and active surface chemistry. A significant challenge for their widespread application is reduced gas uptake in wet conditions, attributed to competitive adsorption between gas and water. Recent studies of gas adsorption in wet materials have typically used small amounts of powdered porous materials (in the milligram range) within very small reactors (1–5 mL). This leaves a gap in knowledge about gas adsorption behaviors in larger reactors and with increased MOF sample sizes (to the gram scale). Additionally, there has been a notable absence of experimental research on MOFs heavily saturated with water. In this study, we aimed to fill the gaps in our understanding of gas adsorption in wet conditions by measuring CH4 adsorption in MOFs. To do this, we used larger MOF samples (in grams) and a large-volume reactor. Our selection of commercially available MOFs, including HKUST-1, ZIF-8, MOF-303, and activated carbon, was based on their widespread application, available previous research, and differences in hydrophobicity. Using a volumetric approach, we measured high-pressure isotherms (at T = 274.15 K) to compare the moles of gas adsorbed under both dry and wet conditions across different MOFs and weights. The experimental results indicate that water decreases total CH4 adsorption in MOFs, with a more pronounced decrease in hydrophilic MOFs compared to hydrophobic ones at lower pressures. However, hydrophilic MOFs exhibited stepped isotherms at higher pressures, suggesting water converts to hydrate, positively impacting total gas uptake. In contrast, the hydrophobic ZIF-8 did not promote hydrate formation due to particle aggregation in the presence of water, leading to a loss of surface area and surface charge. This study highlights the additional challenges associated with hydrate-MOF synergy when experiments are scaled up and larger sample sizes are used. Future studies should consider using monolith or pellet forms of MOFs to address the limitations of powdered MOFs in scale-up studies.
Fault Handling and Localization Strategy Based on Waveform Characteristics Recognition with Coordination of Peterson Coil and Resistance Grounding Method
Authors: Li Zhengyang , Cao Yijia , Chen Chun , Li Yansha , Li Jinglu
Published: July 2024

To address challenges in locating high-impedance grounding faults (HIGFs) and isolating fault areas in resonant grounding systems, this paper proposes a novel fault identification method based on coordinating a Peterson coil and a resistance grounding system. This method ensures power supply reliability by extinguishing the fault arc during transient faults with the Peterson coil. When a fault is determined to be permanent, the neutral point switches to a resistance grounding mode, ensuring regular distribution of zero-sequence currents in the network, thereby addressing the challenges of HIGF localization and fault area isolation. Fault calibration and nature determination rely on recognizing neutral point displacement voltage waveforms and dynamic characteristics, eliminating interference from asymmetric phase voltage variations. Fault area identification involves assessing the polarity of zero-sequence current waveforms attenuation during grounding mode switching, preventing misjudgments in grounding protection due to random initial fault angles and Peterson coil compensation states. Field experiments validate the feasibility of this fault location method and its control strategy.
A Systematic Review on the Path to Inclusive and Sustainable Energy Transitions
Authors: Awolesi Oluwafemi , Salter Corinne A. , Reams Margaret
Published: July 2024

This paper surveys the energy literature and systematically reviews the path to an inclusive and sustainable energy transition by exploring factors that drive the current energy transitions, countries with advanced energy transition programs, and the roles of energy literacy and justice in energy transition. Utilizing an exhaustive literature search from 2001 to 2023 via the Scopus database, the study identifies strong policy frameworks, technological advancements, economic incentives, and international collaborations as pivotal factors in successful energy transitions. Case studies from the Nordic countries, Germany, and Poland highlight diverse approaches and significant progress, revealing valuable lessons for global application. Although energy literacy emerges as crucial for public acceptance and participation, fostering informed decision-making and supportive behaviors toward renewable energy initiatives, energy justice ensures equitable access to the benefits of energy transitions, addressing socio-economic impacts on marginalized communities. The study identifies a scarcity of research that articulates and integrates energy literacy and justice concurrently within the purview of energy transition. The paper recommends the adoption, integration, and institutionalization of frameworks that concurrently propagate energy literacy and guide fair and equitable energy transitions. The frameworks should encourage active community involvement, promote community ownership of renewable energy projects, ensure transparency and inclusivity, implement measures for equitable economic benefits, protect livelihoods, address historical distrust, and leverage social media to promote energy literacy and justice. Finally, the continuous monitoring and evaluation of energy transition initiatives are crucial to ensure that they meet evolving societal needs and environmental goals.
Biochemical and Biorefinery Platform for Second-Generation Bioethanol: Fermentative Strategies and Microorganisms
Authors: González-Gloria Karla D. , Tomás-Pejó Elia , Amaya-Delgado Lorena , Rodríguez-Jasso Rosa M. , Loredo-Treviño Araceli , Singh Anusuiya , Hans Meenu , Martín Carlos , Kumar Sachin , Ruiz Héctor A.
Published: July 2024

Bioethanol is the most commonly used biofuel. It is an alternative to replace fossil fuels in renewable energy; it can be produced from lignocellulosic feedstock using a biotechnological process. Their participation of microorganisms is crucial in the bioconversion process of fermentation for ethanol production and can involve bacteria, fungi, and yeasts. However, when working within bioethanol processes from lignocellulose feedstock, microorganisms face some challenges, such as high temperature, high solids content, and the ability to ferment sugars for high ethanol concentration. Such challenges will depend on operative strategies, such as simultaneous saccharification and fermentation, separate hydrolysis and fermentation, semi-simultaneous saccharification and fermentation, and consolidated bioprocessing; these are the most common configurations. This review presents different trends of the microbial role, biochemical application, and fermentation operative strategies for bioethanol production of the second generation.
SD-GPSR: A Software-Defined Greedy Perimeter Stateless Routing Method Based on Geographic Location Information
Authors: Gao Shaopei , Liu Qiang , Zeng Junjie , Li Li
Published: July 2024

To mitigate the control overhead of Software-Defined Mobile Ad Hoc Networks (SD-MANETs), this paper proposes a novel approach, termed Software-Defined Greedy Perimeter Stateless Routing (SD-GPSR), which integrates geographical location information. SD-GPSR optimizes routing functions by decentralizing them within the data plane of SD-MANET, utilizing the geographic location information of nodes to enhance routing efficiency. The controller is primarily responsible for providing location services and facilitating partial centralized decision-making. Within the data plane, nodes employ an enhanced distance and angle-based greedy forwarding algorithm, denoted as GPSR_DA, to efficiently forward data. Additionally, to address the issue of routing voids in the data plane, we employ the A* algorithm to compute an optimal routing path that circumvents such voids. Finally, we conducted a comparative analysis with several state-of-the-art approaches. The evaluation experiments demonstrate that SD-GPSR significantly reduces the control overhead of the network. Simultaneously, there is a notable improvement in both end-to-end latency and packet loss rate across the network.
A Study on the Impact of Window Partition Walls on the Spread of Fire on Building Facades
Authors: Qin Rongshui , Dai Xuesong , Ding Chao , Zhang Zelong , Jiao Yan , Ren Xin
Published: July 2024

This paper investigates the impact of window partition walls on the spread of fire on building facades under the impact of environmental wind through Fire Dynamics Simulator simulation experiments. A four-story building model was constructed using a Fire Dynamics Simulator incorporating six different wind speed conditions and six different partition wall widths. The fire-blocking performance of window partition walls of varying widths was systematically compared and analyzed, and the data indicated: (1) Under calm wind conditions, the installation of window partition walls is observed to facilitate the vertical spread of facade fires. Moreover, as the width of these partition walls increases, this facilitative effect becomes increasingly prominent; (2) Under wind speeds of 0 to 5 m/s, the temperature on the leeward side is lower when window partition walls are present than when they are absent. This indicates that window partition walls inhibit the horizontal spread of building facade fires, and wider window partition walls have better horizontal fire resistance performance.
Anticancer Potential of Flavonoids: Their Role in Cancer Prevention and Health Benefits
Authors: Pyo Yeonhee , Kwon Ki Han , Jung Yeon Ja
Published: July 2024

The term “flavonoid” encompasses a group of plant compounds, predominantly flavonoids, present in fruits, vegetables, and other plant-based foods. These compounds deliver significant health benefits, including potent antioxidant properties that protect cells from free radicals, thereby mitigating aging and disease. We assessed study quality and bias using the Cochrane Risk of Bias tool and the Newcastle−Ottawa Scale. Inclusion criteria specified that the studies must examine a natural flavonoid from fruits, must involve animal or human trials, must be original studies, and must be English articles on the flavonoid’s health and cancer-prevention effects, excluding conference abstracts and single-case studies. We conducted a comprehensive search of major databases including PubMed, Web of Science, Embase, SCOPUS, and Google Scholar, reviewing six clinical trials with total sample sizes of over 50 to 1500 participants. The results indicate that consuming flavonoid-rich fruits can aid in cancer prevention by targeting angiogenic and cancer-protective pathways. We specifically selected tomatoes, mulberries, Amazon grapes, apples, and citrus fruits due to their well-documented high levels of flavonoids and the robust clinical evidence supporting their physiological effects. In particular, citrus fruits contain additional beneficial phytochemicals that complement the action of flavonoids, enhancing their overall health effects. The anti-cancer mechanisms of flavonoids are not well-defined in the scientific literature, suggesting a gap that this study aims to address. Our study provides novel contributions by demonstrating how flavonoid supplementation induces anti-cancer effects through angiogenesis, anti-inflammatory actions, antioxidant-induced apoptosis, and modulation of pathways like PI3K/Akt and MAPK. These effects were particularly notable in the prevention and progression of breast, colon, liver, and lung cancers, with statistical significance (p < 0.05). By elucidating specific mechanisms and pathways, this study contributes to the understanding of flavonoids’ role in cancer prevention and underscores the potential for developing natural anti-cancer therapeutics through the inclusion of flavonoid-rich fruits in the diet. Future research should focus on randomized controlled trials assessing long-term effects of flavonoid supplementation in diverse populations, exploring optimal dosages, and understanding interactions with conventional cancer therapies to provide comprehensive evidence for clinical applications.
Prehabilitation Consultation on Self-Care and Physical Exercise in Patients Diagnosed with Abdominopelvic Cancer: Protocol of the Study
Authors: Suárez-Alcázar María Pilar , Collado-Boira Eladio J. , Recacha-Ponce Paula , Salas-Medina Pablo , García-Roca M. Elena , Hernando Carlos , Muriach María , Baliño Pablo , Flores-Buils Raquel , Martínez Latorre María Luisa , Sales-Balaguer Nerea , Folch-Ayora A.
Published: July 2024

Background: Introduction: Prehabilitation in the field of oncology has been defined as “the process in the continuum of care that occurs between diagnosis and the start of treatment involving physical and psychological measures that determine the patient’s baseline functional status.” Aim: To determine the effectiveness of a Prehabilitation consultation on self-care and targeted physical exercise for patients diagnosed with abdominopelvic cancer. Design: An observational study that will evaluate the pre-post efficacy of an ad-hoc designed Prehabilitation intervention. The study population consists of patients diagnosed with colon or gynecological cancer with a surgical indication as part of their therapeutic plan from the General Surgery Services. It is configured around four key interventions: (a) health education and self-care, (b) specific nutritional counseling, (c) initial psychological assessment, and (d) directed physical exercise intervention. Health education, self-care interventions, and physical exercise will be carried out weekly from diagnosis to the scheduled surgery day. Results: Aspects such as self-care capacity or agency, perioperative anxiety, aerobic capacity, strength and flexibility, postoperative complications, and recovery time to adjuvant treatment will be measured using tools such as Appraisal of self-care agency scale (ASA), State Trait Anxiety Inventory (STAI), walking test, sit and Reach, Hand Grip or Squad Jump. Conclusion: Utilizing validated tools for analyzing selected variables will contribute to refining and expanding care guidelines, ultimately enhancing support for both patients and their caregivers.
Exploration of the Determinants of Subjective Health and Depression Using Korean Longitudinal Study of Aging Data
Authors: Sun Kyung-A , Moon Joonho
Published: July 2024

Aging is an imperative issue in Korean society, and a healthy life is important for a better quality of life for older adults. Therefore, the purpose of this research was to investigate the determinants of subjective health and depression in middle-aged and elderly Korean individuals. This study used three attributes as the determinants of subjective health and depression, including the curve linear effect of medical expenses and eating-out expenses and the linear impact of regular exercise. We utilized the Korean Longitudinal Study of Aging (KLOSA) to determine the associations between five attributes: subjective health, depression, medical expenses, eating-out expenses, and regular exercise. Research panel data were employed as the data source. The study period was between 2018 and 2020. This research implemented various multiple linear panel regression econometric analysis instruments: ordinary least squares, random effects, and fixed effects. The mean age of survey participants was 72.10 years, and 35 percent of participants were female. The number of observations for data analysis was 7197. The results revealed that medical and eating-out expenses had a curved linear effect on subjective health and depression. Moreover, regular exercise positively affected subjective health and resulted in less depression. These findings may inform policy decisions that promote regular exercise and manage medical and eating-out expenses, thereby enhancing subjective health and mitigating depression.
Safety and Preliminary Efficacy of Cervical Paraspinal Interfascial Plane Block for Postoperative Pain after Pediatric Chiari Decompression
Authors: Pisapia Jared M. , Doherty Tara M. , Grosinger Liana , Huang Audrey , Muh Carrie R. , Abramowicz Apolonia E. , Xu Jeff L.
Published: July 2024

Background: Surgery for lesions of the posterior fossa is associated with significant postoperative pain in pediatric patients related to extensive manipulation of the suboccipital musculature and bone. In this study, we assess the preliminary safety, effect on neuromonitoring, and analgesic efficacy of applying a cervical paraspinal interfascial plane block in pediatric patients undergoing posterior fossa surgery. Methods: In this prospective case series, we enrolled five patients aged 2–18 years undergoing surgery for symptomatic Chiari type I malformation. An ultrasound-guided cervical cervicis plane (CCeP) block was performed prior to the incision. A local anesthetic agent (bupivacaine) and a steroid adjuvant (dexamethasone) were injected into the fascial planes between the cervical semispinalis capitis and cervical semispinalis cervicis muscles at the level of the planned suboccipital decompression and C1 laminectomy. Motor-evoked and somatosensory-evoked potentials were monitored before and after the block. Patients were assessed for complications from the local injection in the intraoperative period and for pain in the postoperative period. Results: No adverse events were noted intraoperatively, and there were no changes in neuromonitoring signals. Pain scores were low in the immediate postoperative period, and rescue medications were minimal. No complaints of incisional pain or need for narcotics were noted at the time of the 3-month postsurgical follow-up. Conclusions: In this study, we demonstrate the preliminary safety and analgesic efficacy of a novel application of a CCeP block to pediatric patients undergoing suboccipital surgery. Larger studies are needed to further validate the use of this block in children.
Effect of a 12-Week Strength Training Program on Muscle Strength Measures of Institutionalized Older Adults—A Pilot Study
Authors: Pereira Bernardo , Monteiro Diogo , Matos Rui , Jacinto Miguel , Amaro Nuno , Antunes Raúl , Rodrigues Filipe
Published: July 2024

Institutionalized older adults are characterized by high levels of dependence and low levels of physical activity compared to those living in the community. This combination of factors leads to an increased risk of loss of muscle mass. Sarcopenia can be countered through strength training. The aim of the present study was to evaluate the effect of a strength training program on the physical fitness of institutionalized older adults. This study included a sample of 31 institutionalized older adults (20 females, 11 males) aged between 65 and 96 years (M = 81.64, SD = 8.67). Participants reported an average institutionalization duration of 2.43 years (SD = 2.20), ranging from half a year to ten years. A 12-week strength training program was implemented, with sessions held twice a week. Strength fitness was assessed through the following parameters: handgrip strength, upper limb muscular endurance, lower limb muscular endurance, agility and balance, body mass index, and waist circumference. The results demonstrated that a 12-week strength training program improved physical fitness in terms of lower limb muscular endurance, upper limb muscular endurance, agility, and dynamic balance (p < 0.05).
Correlation between the Oral and Mental Health of University Students in Serbia—A Cross-Sectional Study
Authors: Janicijevic Nikoleta , Dimovic Tamara , Stajic Dalibor , Djonovic Nela , Vasiljevic Dragan , Tepavcevic Melanija , Stepovic Milos , Delic Simonida , Petrovic Marko , Jovanovic Kristijan , Fetahovic Ermin , Manojlovic Katarina , Petrovic Ivica , Filipovic Milos , Sekulic Marija
Published: July 2024

Background: This cross-sectional study aimed to assess the correlation between subjective oral health status and mental health in a group of university students in Serbia. Methods: The study included 948 students, aged between 18 and 27, from the Faculty of Medical Sciences, University of Kragujevac, Serbia, and was conducted in 2020. The World Health Organization’s Oral Health Questionnaire for Adults was utilized to evaluate the respondents’ self-perceived oral health and oral hygiene practices. The existence of depressive symptoms was evaluated using the Beck Depression Inventory-II (BDI-II), and the Zung self-rating anxiety scale (SAS) was used for determining anxiety symptoms. Results: It is observed that 28.9% of respondents exhibit symptoms of depression and 42.3% showed symptoms of anxiety. Results show that students with severe depression and anxiety symptoms very often reported lower self-perceived oral health and oral health problems. Although the nature of this relationship has not been thoroughly evaluated, several studies have shown a mutually dependent connection between oral health and mental health. Conclusions: The results suggest that some aspects of oral health are associated with higher risks of developing symptoms of depression or anxiety, and vice versa.
Assessment of Multiple Trace Metal Fluxes in a Semi-Arid Watershed Containing Mine Tailing, Using a Multiple Tool Approach (Zaida Mine, Upper Moulouya Watershed, Morocco)
Authors: Mimouni Yassine , Chafi Abdelhafid , Bouabdli Abdelhak , Baghdad Bouamar , Deliege Jean-François
Published: July 2024

Few studies have quantified the complex flux of trace metals from mine tailings to rivers through water erosion, especially in the semi-arid region of North Morocco (Zaida mine) where soil erosion is a severe issue. This study applies (i) methods to understand and estimate the complex flux of trace metals from mine tailings to rivers, using the RUSLE model combined with the concentration of trace metals in the soil and additionally (ii) pollution indices and statistical analyses to assess the sediment contamination by Cd, Cu, Pb, and Zn. Our study revealed that the basin has a low erosion rate, with an average of 9.1 t/ha/yr. Moreover, the soil contamination is particularly high at the north of the mine tailings, as prevailing winds disperse particles across the basin. The assessment of the sediments indicated that Pb is the main contaminant, with concentrations exceeding 200 mg/kg specifically downstream of the tailings. This study also identified high a concentration of trace elements 14 km away from the tailings alongside the Moulouya river, due to the specific hydrological transport patterns in the area. This research contributes to a better understanding of the transport and fate of the trace metals in mining areas. It proposes a replicable method that can be applied in other regions to assess the contamination flows and thereby assist water resource management.
Enhancing Place Emotion Analysis with Multi-View Emotion Recognition from Geo-Tagged Photos: A Global Tourist Attraction Perspective
Authors: Wang Yu , Zhou Shunping , Guan Qingfeng , Fang Fang , Yang Ni , Li Kanglin , Liu Yuanyuan
Published: July 2024

User-generated geo-tagged photos (UGPs) have emerged as a valuable tool for analyzing large-scale tourist place emotions with unprecedented detail. This process involves extracting and analyzing human emotions associated with specific locations. However, previous studies have been limited to analyzing individual faces in the UGPs. This approach falls short of representing the contextual scene characteristics, such as environmental elements and overall scene context, which may contain implicit emotional knowledge. To address this issue, we propose an innovative computational framework for global tourist place emotion analysis leveraging UGPs. Specifically, we first introduce a Multi-view Graph Fusion Network (M-GFN) to effectively recognize multi-view emotions from UGPs, considering crowd emotions and scene implicit sentiment. After that, we designed an attraction-specific emotion index (AEI) to quantitatively measure place emotions based on the identified multi-view emotions at various tourist attractions with place types. Complementing the AEI, we employ the emotion intensity index (EII) and Pearson correlation coefficient (PCC) to deepen the exploration of the association between attraction types and place emotions. The synergy of AEI, EII, and PCC allows comprehensive attraction-specific place emotion extraction, enhancing the overall quality of tourist place emotion analysis. Extensive experiments demonstrate that our framework enhances existing place emotion analysis methods, and the M-GFN outperforms state-of-the-art emotion recognition methods. Our framework can be adapted for various geo-emotion analysis tasks, like recognizing and regulating workplace emotions, underscoring the intrinsic link between emotions and geographic contexts.
Sensing the Environmental Inequality of PM2.5 Exposure Using Fine-Scale Measurements of Social Strata and Citizenship Identity
Authors: He Li , He Lingfeng , Lin Zezheng , Lu Yao , Chen Chen , Wang Zhongmin , An Ping , Liu Min , Xu Jie , Gao Shurui
Published: July 2024

Exposure to PM2.5 pollution poses substantial health risks, with the precise quantification of exposure being fundamental to understanding the environmental inequalities therein. However, the absence of high-resolution spatiotemporal ambient population data, coupled with an insufficiency of attribute data, impedes a comprehension of the environmental inequality of exposure risks at a fine scale. Within the purview of a conceptual framework that interlinks social strata and citizenship identity with environmental inequality, this study examines the environmental inequality of PM2.5 exposure with a focus on the city of Xi’an. Quantitative metrics of the social strata and citizenship identities of the ambient population are derived from housing price data and mobile phone big data. The fine-scale estimation of PM2.5 concentrations is predicated on the kriging interpolation method and refined by leveraging an advanced dataset. Employing geographically weighted regression models, we examine the environmental inequality pattern at a fine spatial scale. The key findings are threefold: (1) the manifestation of environmental inequality in PM2.5 exposure is pronounced among individuals of varying social strata and citizenship identities within our study area, Xi’an; (2) nonlocal residents situated in the northwestern precincts of Xi’an are subject to the most pronounced PM2.5 exposure; and (3) an elevated socioeconomic status is identified as an attenuating factor, capable of averting the deleterious impacts of PM2.5 exposure among nonlocal residents. These findings proffer substantial practical implications for the orchestration of air pollution mitigation strategies and urban planning initiatives. They suggest that addressing the wellbeing of the marginalized underprivileged cohorts, who are environmentally and politically segregated under the extant urban planning policies in China, is of critical importance.
The GLP-1 Receptor Agonist Liraglutide Decreases Primary Bile Acids and Serotonin in the Colon Independently of Feeding in Mice
Authors: Nonogaki Katsunori , Kaji Takao
Published: July 2024

Liraglutide, a glucagon-like peptide 1 analog used to treat type 2 diabetes and obesity, is a potential new treatment modality for bile acid (BA) diarrhea. Here, we show that administration of liraglutide significantly decreased total BAs, especially the primary BAs, including cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, and β-muricholic acid, in the liver and feces. In addition, liraglutide significantly decreased tryptophan metabolites, including L-tryptophan, serotonin, 5-hydroxy indole-3-acetic acid, L-kynurenine, and xanthurenic acid, in the colon, whereas it significantly increased indole-3-propionic acid. Moreover, the administration of liraglutide remarkably decreased the expression of apical sodium-dependent bile acid transporter, which mediates BA uptake across the apical brush border member in the ileum, ileal BA binding protein, and fibroblast growth factor 15 in association with decreased expression of the BA-activated nuclear receptor farnesoid X receptor and the heteromeric organic solute transporter Ostα/β, which induces BA excretion, in the ileum. Liraglutide acutely decreased body weight and blood glucose levels in association with decreases in plasma insulin and serotonin levels in food-deprived mice. These findings suggest the potential of liraglutide as a novel inhibitor of primary BAs and serotonin in the colon.
Uncovering the Molecular Pathways Implicated in the Anti-Cancer Activity of the Imidazoquinoxaline Derivative EAPB02303 Using a Caenorhabditis elegans Model
Authors: Makhoul Perla , Galas Simon , Paniagua-Gayraud Stéphanie , Deleuze-Masquefa Carine , Hajj Hiba El , Bonnet Pierre-Antoine , Richaud Myriam
Published: July 2024

Imiqualines are analogues of the immunomodulatory drug imiquimod. EAPB02303, the lead of the second-generation imiqualines, is characterized by significant anti-tumor effects with IC50s in the nanomolar range. We used Caenorhabditis elegans transgenic and mutant strains of two key signaling pathways (PI3K-Akt and Ras-MAPK) disrupted in human cancers to investigate the mode of action of EAPB02303. The ability of this imiqualine to inhibit the insulin/IGF1 signaling (IIS) pathway via the PI3K-Akt kinase cascade was explored through assessing the lifespan of wild-type worms. Micromolar doses of EAPB02303 significantly enhanced longevity of N2 strain and led to the nuclear translocation and subsequent activation of transcription factor DAF-16, the only forkhead box transcription factor class O (Fox O) homolog in C. elegans. Moreover, EAPB02303 significantly reduced the multivulva phenotype in let-60/Ras mutant strains MT2124 and MT4698, indicative of its mode of action through the Ras pathway. In summary, we showed that EAPB02303 potently reduced the activity of IIS and Ras-MAPK signaling in C. elegans. Our results revealed the mechanism of action of EAPB02303 against human cancers associated with hyperactivated IIS pathway and oncogenic Ras mutations.
Medicinal Plant Root Exudate Metabolites Shape the Rhizosphere Microbiota
Authors: Qu Peng , Wang Butian , Qi Meijun , Lin Rong , Chen Hongmei , Xie Chun , Zhang Zhenwei , Qiu Junchao , Du Huabo , Ge Yu
Published: July 2024

The interactions between plants and rhizosphere microbes mediated by plant root exudates are increasingly being investigated. The root-derived metabolites of medicinal plants are relatively diverse and have unique characteristics. However, whether medicinal plants influence their rhizosphere microbial community remains unknown. How medicinal plant species drive rhizosphere microbial community changes should be clarified. In this study involving high-throughput sequencing of rhizosphere microbes and an analysis of root exudates using a gas chromatograph coupled with a time-of-flight mass spectrometer, we revealed that the root exudate metabolites and microorganisms differed among the rhizosphere soils of five medicinal plants. Moreover, the results of a correlation analysis indicated that bacterial and fungal profiles in the rhizosphere soils of the five medicinal plants were extremely significantly or significantly affected by 10 root-associated metabolites. Furthermore, among the 10 root exudate metabolites, two (carvone and zymosterol) had opposite effects on rhizosphere bacteria and fungi. Our study findings suggest that plant-derived exudates modulate changes to rhizosphere microbial communities.
Variations of VEGFR2 Chemical Space: Stimulator and Inhibitory Peptides
Authors: Lungu Claudiu N. , Mangalagiu Ionel I. , Gurau Gabriela , Mehedinti Mihaela Cezarina
Published: July 2024

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR type 2 angiogenesis and vascular morphogenesis as the tyrosine kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between Vascular Endothelial Growth Factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.
Guardians under Siege: Exploring Pollution’s Effects on Human Immunity
Authors: Drago Gaspare , Aloi Noemi , Ruggieri Silvia , Longo Alessandra , Contrino Maria Lia , Contarino Fabio Massimo , Cibella Fabio , Colombo Paolo , Longo Valeria
Published: July 2024

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body’s defense systems going beyond the well-established associations with defense systems and delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.
Mechanistic Insights of Neuroprotective Efficacy of Verapamil-Loaded Carbon Quantum Dots against LPS-Induced Neurotoxicity in Rats
Authors: Mosalam Esraa M. , Elberri Aya Ibrahim , Abdallah Mahmoud S. , Abdel-Bar Hend Mohamed , Zidan Abdel-Aziz A. , Batakoushy Hany A. , Abo Mansour Hend E.
Published: July 2024

Alzheimer’s disease (AD) is a neurodegenerative disease that badly impacts patients and their caregivers. AD is characterized by deposition of amyloid beta (Aβ) and phosphorylated tau protein (pTau) in the brain with underlying neuroinflammation. We aimed to develop a neuroprotective paradigm by loading verapamil (VRH) into hyaluronic acid-modified carbon quantum dots (CQDs) and comparing its effectiveness with the free form in an AD-like model in rats induced by lipopolysaccharide (LPS). The experimental rats were divided into seven groups: control, LPS, CQDs, early free VRH (FVRH), late FVRH, early verapamil carbon quantum dots (VCQDs), and late VCQDs. Characterizations of VCQDs, the behavioral performance of the rats, histopathological and immunohistochemical changes, some AD hallmarks, oxidative stress biomarkers, neuro-affecting genes, and DNA fragmentation were determined. VRH was successfully loaded into CQDs, which was confirmed by the measured parameters. VRH showed enhancement in cognitive functions, disruption to the architecture of the brain, decreased Aβ and pTau, increased antioxidant capacity, modifiable expression of genes, and a decline in DNA fragmentation. The loaded therapy was superior to the free drug. Moreover, the early intervention was better than the late, confirming the implication of the detected molecular targets in the development of AD. VRH showed multifaceted mechanisms in combating LPS-induced neurotoxicity through its anti-inflammatory and antioxidant properties, thereby mitigating the hallmarks of AD. Additionally, the synthesized nanosystem approach exhibited superior neuroprotection owing to the advantages offered by CQDs. However, finding new actionable biomarkers and molecular targets is of decisive importance to improve the outcomes for patients with AD.
An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy
Authors: Segarra-Casas Alba , Yépez Vicente A. , Demidov German , Laurie Steven , Esteve-Codina Anna , Gagneur Julien , Parkhurst Yolande , Muni-Lofra Robert , Harris Elizabeth , Marini-Bettolo Chiara , Straub Volker , Töpf Ana
Published: July 2024

Duchenne and Becker muscular dystrophies, caused by pathogenic variants in DMD, are the most common inherited neuromuscular conditions in childhood. These diseases follow an X-linked recessive inheritance pattern, and mainly males are affected. The most prevalent pathogenic variants in the DMD gene are copy number variants (CNVs), and most patients achieve their genetic diagnosis through Multiplex Ligation-dependent Probe Amplification (MLPA) or exome sequencing. Here, we investigated a female patient presenting with muscular dystrophy who remained genetically undiagnosed after MLPA and exome sequencing. RNA sequencing (RNAseq) from the patient’s muscle biopsy identified an 85% reduction in DMD expression compared to 116 muscle samples included in the cohort. A de novo balanced translocation between chromosome 17 and the X chromosome (t(X;17)(p21.1;q23.2)) disrupting the DMD and BCAS3 genes was identified through trio whole genome sequencing (WGS). The combined analysis of RNAseq and WGS played a crucial role in the detection and characterisation of the disease-causing variant in this patient, who had been undiagnosed for over two decades. This case illustrates the diagnostic odyssey of female DMD patients with complex structural variants that are not detected by current panel or exome sequencing analysis.
Autonomous Oscillatory Mitochondrial Respiratory Activity: Results of a Systematic Analysis Show Heterogeneity in Different In Vitro-Synchronized Cancer Cells
Authors: Cela Olga , Scrima Rosella , Pacelli Consiglia , Rosiello Michela , Piccoli Claudia , Capitanio Nazzareno
Published: July 2024

Circadian oscillations of several physiological and behavioral processes are an established process in all the organisms anticipating the geophysical changes recurring during the day. The time-keeping mechanism is controlled by a transcription translation feedback loop involving a set of well-characterized transcription factors. The synchronization of cells, controlled at the organismal level by a brain central clock, can be mimicked in vitro, pointing to the notion that all the cells are endowed with an autonomous time-keeping system. Metabolism undergoes circadian control, including the mitochondrial terminal catabolic pathways, culminating under aerobic conditions in the electron transfer to oxygen through the respiratory chain coupled to the ATP synthesis according to the oxidative phosphorylation chemiosmotic mechanism. In this study, we expanded upon previous isolated observations by utilizing multiple cell types, employing various synchronization protocols and different methodologies to measure mitochondrial oxygen consumption rates under conditions simulating various metabolic stressors. The results obtained clearly demonstrate that mitochondrial respiratory activity undergoes rhythmic oscillations in all tested cell types, regardless of their individual respiratory proficiency, indicating a phenomenon that can be generalized. However, notably, while primary cell types exhibited similar rhythmic respiratory profiles, cancer-derived cell lines displayed highly heterogeneous rhythmic changes. This observation confirms on the one hand the dysregulation of the circadian control of the oxidative metabolism observed in cancer, likely contributing to its development, and on the other hand underscores the necessity of personalized chronotherapy, which necessitates a detailed characterization of the cancer chronotype.
Auto/Paracrine C-Type Natriuretic Peptide/Cyclic GMP Signaling Prevents Endothelial Dysfunction
Authors: Werner Franziska , Naruke Takashi , Sülzenbrück Lydia , Schäfer Sarah , Rösch Melanie , Völker Katharina , Krebes Lisa , Abeßer Marco , Möllmann Dorothe , Baba Hideo A. , Schweda Frank , Zernecke Alma , Kuhn Michaela
Published: July 2024

Endothelial dysfunction is cause and consequence of cardiovascular diseases. The endothelial hormone C-type natriuretic peptide (CNP) regulates vascular tone and the vascular barrier. Its cGMP-synthesizing guanylyl cyclase-B (GC-B) receptor is expressed in endothelial cells themselves. To characterize the role of endothelial CNP/cGMP signaling, we studied mice with endothelial-selective GC-B deletion. Endothelial EC GC-B KO mice had thicker, stiffer aortae and isolated systolic hypertension. This was associated with increased proinflammatory E-selectin and VCAM-1 expression and impaired nitric oxide bioavailability. Atherosclerosis susceptibility was evaluated in such KO and control littermates on Ldlr (low-density lipoprotein receptor)-deficient background fed a Western diet for 10 weeks. Notably, the plaque areas and heights within the aortic roots were markedly increased in the double EC GC-B/Ldlr KO mice. This was accompanied by enhanced macrophage infiltration and greater necrotic cores, indicating unstable plaques. Finally, we found that EC GC-B KO mice had diminished vascular regeneration after critical hind-limb ischemia. Remarkably, all these genotype-dependent changes were only observed in female and not in male mice. Auto/paracrine endothelial CNP/GC-B/cGMP signaling protects from arterial stiffness, systolic hypertension, and atherosclerosis and improves reparative angiogenesis. Interestingly, our data indicate a sex disparity in the connection of diminished CNP/GC-B activity to endothelial dysfunction.
Skin Malignant Melanoma and Matrix Metalloproteinases: Promising Links to Efficient Therapies
Authors: Lazar Angela Madalina , Costea Daniel Ovidiu , Popp Cristiana Gabriela , Mastalier Bogdan
Published: July 2024

Skin malignant melanoma (MM) is one of the most frequent and aggressive neoplasia worldwide. Its associated high mortality rates are mostly due to its metastases, while diagnosis and treatment of MM in its early stages is of favorable prognostic. Even skin superficial MMs at incipient local stages can already present with lymph node invasion and distant metastases. Therefore, knowledge of the controllable risk factors and pathogenic mechanisms of MM development, spreading, and metastatic pattern, as well as early diagnosis, are essential to decrease the high mortality rates associated with cutaneous malignant melanoma. Genetic factors are incriminated, although lifetime-acquired genetic mutations appear to be even more frequently involved in the development of MM. Skin melanocytes divide only twice per year and have time to accumulate genetic mutations as a consequence of environmental aggressive factors, such as UV exposure. In the search for more promising therapies, matrix metalloproteinases have become of significant interest, such as MMP-1, MMP-2, MMP-9, and MMP-13, which have been linked to more aggressive forms of cancer and earlier metastases. Therefore, the development of specific synthetic inhibitors of MMP secretion or activity could represent a more promising and effective approach to the personalized treatment of MM patients.
In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent
Authors: Taoussi Omayema , Bambagiotti Giulia , Gameli Prince Sellase , Daziani Gloria , Tavoletta Francesco , Tini Anastasio , Basile Giuseppe , Lo Faro Alfredo Fabrizio , Carlier Jeremy
Published: July 2024

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused “other anabolic agent” (subclass S1.2. of the “anabolic agents” class S1) from the World Anti-Doping Agency’s (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.