bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Building Level of Detail Modelling Strategies: Insights into Building and Urban Energy Modelling
Authors: Bishop Daniel , Mohkam Mahdi , Williams Baxter L. M. , Wu Wentao , Bellamy Larry
Published: September 2024

Level of detail (LoD) is an important factor in urban building energy modelling (UBEM), affecting functionality and accuracy. This work assesses the impacts of the LoD of the roof, window, and zoning on a comprehensive range of outcomes (annual heating load, peak heating demand, overheating, and time-series heating error) in a representative New Zealand house. Lower-LoD roof scenarios produce mean absolute error results ranging from 1.5% for peak heating power to 99% for overheating. Windows and shading both affect solar gains, so lower-LoD windows and/or shading elements can considerably reduce model accuracy. The LoD of internal zoning has the greatest effect on time-series accuracy, producing mean absolute heating error of up to 66 W. These results indicate that low-LoD “shoebox” models, common in UBEM, can produce significant errors which aggregate at scale. Accurate internal zoning models and accurate window size and placement have the greatest potential for error reduction, but their implementation is limited at scale due to data availability and automation barriers. Conversely, modest error reductions can be obtained via simple model improvements, such as the inclusion of eaves and window border shading. Overall, modellers should select LoD elements according to specific accuracy requirements.
Fireground Recognition and Spatio-Temporal Scalability Research Based on ICESat-2/ATLAS Vertical Structure Parameters
Authors: Cao Guojun , Wei Xiaoyan , Ye Jiangxia
Published: September 2024

In the ecological context of global climate change, ensuring the stable carbon sequestration capacity of forest ecosystems, which is among the most important components of terrestrial ecosystems, is crucial. Forest fires are disasters that often burn vegetation and damage forest ecosystems. Accurate recognition of firegrounds is essential to analyze global carbon emissions and carbon flux, as well as to discover the contribution of climate change to the succession of forest ecosystems. The common recognition of firegrounds relies on remote sensing data, such as optical data, which have difficulty describing the characteristics of vertical structural damage to post-fire vegetation, whereas airborne LiDAR is incapable of large-scale observations and has high costs. The new generation of satellite-based photon counting radar ICESat-2/ATLAS (Advanced Topographic Laser Altimeter System, ATLAS) data has the advantages of large-scale observations and low cost. The ATLAS data were used in this study to extract three significant parameters, namely general, canopy, and topographical parameters, to construct a recognition index system for firegrounds based on vertical structure parameters, such as the essential canopy, based on machine learning of the random forest (RF) and extreme gradient boosting (XGBoost) classifiers. Furthermore, the spatio-temporal parameters are more accurate, and widespread use scalability was explored. The results show that the canopy type contributed 79% and 69% of the RF and XGBoost classifiers, respectively, which indicates the feasibility of using ICESat-2/ATLAS vertical structure parameters to identify firegrounds. The overall accuracy of the XGBoost classifier was slightly greater than that of the RF classifier according to 10-fold cross-validation, and all the evaluation metrics were greater than 0.8 after the independent sample test under different spatial and temporal conditions, implying the potential of ICESat-2/ATLAS for accurate fireground recognition. This study demonstrates the feasibility of ATLAS vertical structure parameters in identifying firegrounds and provides a novel and effective way to recognize firegrounds based on different spatial–temporal vertical structure information. This research reveals the feasibility of accurately identifying fireground based on parameters of ATLAS vertical structure by systematic analysis and comparison. It is also of practical significance for economical and effective precise recognition of large-scale firegrounds and contributes guidance for forest ecological restoration.
Effect of Near-Freezing Storage Combined with High-Voltage Electric Fields on the Freshness of Large Yellow Croaker
Authors: Zhang Hui , Yang Qizhang , Lin Songyi , Yan Zhaobin , Wu Xuancheng , Wei Wenqiang , Pang Guibing
Published: September 2024

Seafood is highly perishable after being caught, making effective preservation technology essential. A few studies have explored the mechanisms of near-freezing storage combined with high-voltage electric fields for seafood preservation. This study uses near-freezing storage at −1 °C in conjunction with three high-voltage electric fields (5 kV/m, 8 kV/m, and 16 kV/m) to store large yellow croakers for 21 days and assesses their quality through sensory evaluation, pH values, malondialdehyde, total volatile basic nitrogen, and total viable counts. The results indicate that high-voltage electric fields effectively inhibit endogenous enzyme activity and microbial growth while reducing lipid oxidation in large yellow croakers. The preservation effect is optimal at an electric field strength of 16 kV/m, extending their shelf life by 9 days. These findings offer valuable theoretical and data-driven insights for applying near-freezing storage and electric field preservation technology in cross-regional fish transportation.
Production of Long Fermentation Bread with Jabuticaba Peel Flour Added: Technological and Functional Aspects and Impact on Glycemic and Insulinemic Responses
Authors: Takemura Miriam Regina Canesin , da Graça Juliana Silva , Furtado Marianna Miranda , Marques Marcella Camargo , Sant’Ana Anderson S. , Maróstica Junior Mário Roberto , Mariutti Lilian Regina Barros , Geloneze Bruno , Cazarin Cinthia Baú Betim
Published: September 2024

The consumption of jabuticaba (Plinia cauliflora), a native Brazilian fruit, has shown promising results concerning some metabolic disorders. Therefore, studying it may aid in the development of products capable of preventing or delaying pathological conditions. The objective of the present study was to formulate a functional sourdough bread with the inclusion of jabuticaba peel flour (JPF) and to evaluate the effect on the postprandial response. The proximate composition of the JPF and bread, the stability of the antioxidant compounds after baking, and the functional activity in a clinical trial were carried out to develop the product and guarantee its quality. JPF increased the fiber content of the bread in comparison to the control from 1.0 g/100 g to 2.3–2.9 g/100 g. Also, the antioxidant capacity increased 1.35 to 3.53 times by adding JPF to the bread, as well as the total reducing capacity (1.56 to 2.67 times). The bread’s shelf life was guaranteed for seven days. In the clinical trial, the consumption of control bread resulted in a glycemia peak at 30 min, remaining high until 45 min; for the JPF bread, we noticed a less prominent peak at 45 min and a decrease with less inflection until 180 min. The serum antioxidant capacity of the individuals increased after the 3 h. Although no statistical difference was observed between the groups in the satiety profile, JPF bread presented higher scores after 60 min. Furthermore, a lessened desire to eat other foods and hunger was observed after consuming JPF bread. The inclusion of JPF in the bread manufacturing process promoted a longer shelf life and increased nutritional quality.
Effects of Temperature and Time on the Denaturation of Transforming Growth Factor Beta-1 and Cytokines from Bovine Platelet-Rich Gel Supernatants
Authors: Carmona Jorge U. , López Catalina
Published: September 2024

There is a lack of information about transforming growth factor beta-1 (TGF-β1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was activated with calcium gluconate. Thereafter, P-PRG and their supernatants (P-PRGS) were maintained at −80, −20, 4, 21, and 37 °C and collected at 3, 6, 12, 24, 48, 96, 144, 192, 240, and 280 h for subsequent determination of TGF-β1, tumor necrosis factor alfa (TNF-α), interleukin (IL)-2, and IL-6; TGF-β1 concentrations were significantly (p < 0.05) higher in PRGS maintained at 21 and 37 °C when compared to PRGS maintained at 4, −20, and −80 °C; PRGS TNF-α concentrations were not influenced by temperature and time factors. However, PRGS maintained at 4 °C showed significantly (p < 0.05) higher concentrations when compared to PRGS maintained at −20, and −80 °C at 144, and 192 h. IL-6 concentrations were significantly (p < 0.05) higher in PRGS stored at −20, and −80 over the first 48 h and at 10 days when compared to PRGS stored at 4, 21, and 37 °C. These results could suggest that P-PRP/P-PRGS could be maintained and well preserved for at least 12 days at room temperature for clinical use in bovine therapeutic massive protocols.
“And What If You Can’t Forget It? … What If It Stays in Your Head, Repeating Itself … ?”: Reading Chuck Palahniuk’s Horror Trilogy (Lullaby, Diary, and Haunted) for Obsessions and Compulsions
Authors: Van-Hagen Steve
Published: September 2024

This essay argues that one of the distinguishing characteristics of Chuck Palahniuk’s self-described “Horror Trilogy” of novels, Lullaby, Diary, and Haunted, is their representation of obsessions, compulsions, and obsessive–compulsive disorders. This essay analyses these representations from a variety of different perspectives, including medical and psychiatric approaches, clinical and self-help narratives, and biocultural readings emanating from cultural history and critical disability studies. It is demonstrated that the novels reflect a range of the debates that arise from these competing approaches, and the points of similarity and difference in the readings produced are identified. Palahniuk’s representations, it is suggested, must be seen in the contexts of a number of his recurrent thematic preoccupations, and of his engagement with existential comedy. Ultimately, this essay suggests that Palahniuk’s representations of obsessions, compulsions, and OCD must be seen as multi-faceted and protean, as befitting the awareness of the complicated current debates about their conceptualisation that the novels display.
“Still Cool as a Zombie”: Community, the Zombie Aesthetic, and the Politics of Belonging
Authors: Cox Colin A.
Published: September 2024

From Night of the Living Dead (1968) to The Walking Dead (2010–2022), zombie media offers a consistent refrain, namely to avoid becoming a zombie. This refrain makes intuitive sense. Why would anyone welcome becoming a member of a roaming, mindless, and often violent undead horde symbolizing humanity’s destruction? However, zombification has affirmative, emancipatory possibilities. In “Epidemiology,” from Season 2 of the NBC sitcom Community (2009–2015), we see the zombie’s affirmative and emancipatory potential. In this essay, I argue zombification enlivens Community by provoking the show to rethink its relationship to its nominal protagonist, Jeff Winger, and to itself as a piece of avant-garde comedy television produced during the “Golden Age of Television,” what media scholars also call, “Peak” or “Prestige TV.” In this episode, Community evolves its understanding of its central protagonist by shifting, in some respects, from a conventional and historically predictable character to a character far less conventional.
Colorectal Cancer and Asbestos Exposure: A Women’s Health Perspective
Authors: Porzio Antonietta , Feola Alessandro , Salzillo Cecilia , Corbi Graziamaria , Campobasso Carlo Pietro
Published: September 2024

Background: Colorectal cancer (CRC) is considered a “man’s disease”. However, emerging data show that females may have a higher prevalence of certain risk factors. A potential causal role of asbestos in CRC carcinogenesis has been suggested. This relationship is controversial, and only a few studies have focused on exposed female populations. The aim of this study was to review the scientific literature related to asbestos-related CRC incidence and mortality rates in female populations to address gender bias in the existing research. Methods: A systematic review was performed following PRISMA statement. Results: Fourteen studies reporting 92 cases in total were included. Most women were aged 50 years or older and were employed in occupational activities with high asbestos exposure (steel, textile, and asbestos-cement industry) for at least 10 years. In one single case, household asbestos exposure was reported. The colon was the primary location of the tumor in 47 out of 92 cases. Three women were also affected by synchronous or metachronous peritoneal mesotheliomas. Conclusions: This study revealed a general methodological “gender bias” in scientific research. A significantly higher representation of women in clinical studies is needed to clarify the link between asbestos exposure and the development of colorectal cancer.
Informed Consent in Clinical Training: Perspectives from Medical Students and Faculty in Portugal
Authors: Moreira Carolina Frade , Costa-Santos Cristina , Moreira Bárbara Frade , Nunes Rui , Duarte Ivone
Published: September 2024

The student–patient relationship represents the cornerstone of medical education, shaping future doctors’ knowledge, skills and attitudes. While most patients allow student involvement in their care, some may express discomfort. Thus, obtaining explicit consent is essential to respect patients’ right of autonomy. This study mainly aims to assess the practical application of informed consent by medical students and teachers regarding students’ presence and participation in patients’ care. An observational cross-sectional study was performed, and an online questionnaire was given to students and teachers at a single medical school, via institutional email. The study included 289 participants, namely 232 students and 57 teachers. While 81% of teachers reported always asking the patient’s consent for students’ presence, only 28% of students claimed this to be the case. Despite challenges like overcrowding and limited time, involving students in healthcare benefits both students and patients. Moreover, medical ethics education is crucial to foster compassionate care and promote ethical reasoning. The disparities found between teachers’ practices and students’ perspectives highlight the need to intervene and provide them with an adequate education on ethical values in clinical practice. Strategic interventions at institutional levels are required for a simultaneous high quality of patient care and clinical training.
Burnout and Coping Strategies in Integrative Psychotherapists: Findings from Qualitative Interviews
Authors: Tragantzopoulou Panagiota , Giannouli Vaitsa , Filippou Anna , Demirtzidou Margarita
Published: September 2024

Burnout among psychotherapists is a pervasive challenge affecting both professional well-being and client care. This study aims to explore the experience of burnout among integrative psychotherapists and examine the strategies they employ to cope with this phenomenon. Interviews were conducted with 17 integrative psychotherapists, and the data were analyzed using Braun and Clarke’s six-step thematic analysis. Through this analysis, two themes were identified: (1) work-related pressures and burnout manifestations and (2) strategies for maintaining optimal functioning. Fatigue, headaches, challenges in decision-making or session planning, numbness in the form of paralysis, and disconnection from clients emerged as primary symptoms, impacting therapeutic efficacy. Participants’ intense sense of responsibility toward clients and their self-worth validation through client progress intensified burnout risks, particularly among novices. Personal therapy and clinical supervision emerged as pivotal in mitigating burnout, offering support, and enhancing therapist resilience. Additionally, peer support and organizational interventions were deemed crucial during crises, emphasizing the need for structured support systems within professional bodies. These findings contribute to a deeper understanding of burnout in psychotherapy and highlight the need for targeted interventions to enhance professionals’ resilience and sustain effective client outcomes.
Potential Impact of Physical Activity on Measures of Well-Being and Quality of Life in People with Rare Diseases: A Nationwide Cross-Sectional Study in Italy
Authors: Aliberti Silvana Mirella , Sacco Anna Maria , Belviso Immacolata , Romano Veronica , Di Martino Aldo , Russo Ettore , Collet Stefania , Ciancaleoni Bartoli Ilaria , Tuzi Manuel , Capunzo Mario , Donato Antonio , Castaldo Clotilde , Di Meglio Franca , Nurzynska Daria
Published: September 2024

Background: Rare diseases constitute a heterogeneous group of approximately 7000–8000 conditions, distinguished by their low prevalence. Collectively, they present a significant global health challenge, affecting millions of people worldwide. It is estimated that rare diseases affect approximately 10% of the global population, which places a significant burden on individuals, families, and society. It is, therefore, important to consider strategies to improve the overall well-being and quality of life of individuals with rare diseases. One potential avenue for exploration is the incorporation of physical activity (PA). The scope of this study was to ascertain whether PA has a positive impact on measures of well-being and to determine its potential to enhance the quality of life of these individuals. Methods: The data were collected via an online survey. The one-way ANOVA test for multiple groups and multivariate Poisson models were employed to identify the significant predictors of the outcomes of interest. Results: The protective effects of PA become evident with a minimum of six hours of activity per week. Our data confirm that the weekly hours devoted to PA can serve as a significant protective factor for QoL. The study also provided some insights into the motivations behind patients’ engagement in PA. These included improving QoL and physical well-being, as well as the desire to interact socially, with the goal of meeting friends or making new acquaintances. Finally, for adults and older adults, engaging in PA can also be a way to control weight. Conclusions: It is becoming increasingly clear that individuals with rare diseases stand to benefit greatly from PA, so it is only sensible to educate them on the advantages of an active lifestyle.
Physiological Responses and Quality Alterations of Pea Sprouts under Salt Stress: Implications for Salt-Tolerant Mechanism
Authors: Guo Juxian , Zhan Liqing , Su Xiuxiu , Wang Tingqin
Published: September 2024

Pea sprouts, considered a nutritious and environmentally sustainable vegetable with significant cultivation prospects and market potential, face growth challenges due to salt stress. However, the underlying mechanisms associated with this stress have not been fully elucidated. To address this knowledge gap, we conducted a hydroponic study applying various concentrations of NaCl salt stress to pea sprouts. Systematic analysis was performed on key parameters including germination, plant height, biomass, and enzyme activity of pea sprouts under salt treatment. Our aim was to unravel the underlying mechanisms associated with the impact of salt stress on the growth of pea sprouts. Results revealed that salt treatment significantly inhibited the germination process of pea sprouts’ seeds, leading to a notable decrease in plant height and sprout yield. Salt stress induced an increase in MDA content, a decrease in chlorophyll content, and elevated relative conductivity. However, a low concentration of salt treatment enhanced SOD activity, suggesting the activation of oxidative stress resistance mechanisms in pea sprouts. Moreover, salt treatment exhibited an inhibitory effect on soluble protein content while promoting soluble sugar content in pea sprouts. Additionally, low-concentration salt treatment increased the crude fiber content of pea sprouts, while high-concentration salt treatment inhibited it. In summary, this study indicates that salt stress could cause physiological damage to pea sprouts, but pea sprouts may employ metabolic strategies to adapt to the low concentration of salt stress. These findings contribute to a deeper understanding of the physiological responses of pea sprouts to salt stress and provide valuable insights for its implementation of salt-tolerant cultivation.
Dormancy-Related Bioactive Compounds and Antioxidant Activity during Optimization of Germination Conditions for Onopordum nervosum subsp. platylepis Murb. Using Response Surface Methodology
Authors: Dhen Najla , Kouki Rania , Bziouech Samra Akef , Essaidi Ismahen , Naffati Lamia , Haouala Faouzi , Alhudhaibi Abdulrahman M. , Alrudayni Hassan A. , Kammoun Mariem , Al Mohandes Dridi Bouthaina
Published: September 2024

Onopordum nervosum subsp. platylepis Murb. is an Asteraceae species found in Tunisia, Algeria, and Libya. It has been studied for its potential use as a vegetable rennet alternative to animal-derived rennet, making it important to understand its germination characteristics. This species often shows low germinability due to dormancy, which limits its large-scale cultivation. In preliminary experiments, many factors were analyzed to evaluate the seed germination of this thistle including physical stratification with abrasive paper and high-temperature water, chemical treatments with hydrogen peroxide (H2O2) or sulfuric acid (H2SO4), and the exogenous use of the growth regulator gibberellic acid (GA3). Based on the obtained results and subsequent analysis, GA3 and cold stratification durations were selected for the second experiment, which used a full factorial RSM design with three levels for each factor. Additionally, the total polyphenol content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), and DPPH assay were analyzed during the optimization process and for ungerminated seeds. The findings revealed that 14 days of cold stratification followed by 750 ppm GA3 was the most efficient method for breaking the dormancy of these thistle seeds. The highest TPC was recorded in ungerminated seeds. However, germinated Onopordum nervosum ssp. platylepis seeds showed higher levels of TFC and CTC (14.83 mg QE/g DW and 6.49 mg EC/g DW, respectively) compared to the non-germinated ones and demonstrated the greatest potency in inhibiting free radicals (DPPH EC50 = 0.018 mg/mL) at the identified optimal germination conditions. Ungerminated seeds indicated significant phenolic content (TPC) and a limited ability to reduce oxidants, which could explain their low germination percentage. Our findings on the seed germination and dormancy characteristics of this endemic thistle will aid in the protection and development of its germplasm.
The Implementation of Multimodal Large Language Models for Hydrological Applications: A Comparative Study of GPT-4 Vision, Gemini, LLaVa, and Multimodal-GPT
Authors: Kadiyala Likith Anoop , Mermer Omer , Samuel Dinesh Jackson , Sermet Yusuf , Demir Ibrahim
Published: September 2024

Large Language Models (LLMs) combined with visual foundation models have demonstrated significant advancements, achieving intelligence levels comparable to human capabilities. This study analyzes the latest Multimodal LLMs (MLLMs), including Multimodal-GPT, GPT-4 Vision, Gemini, and LLaVa, with a focus on hydrological applications such as flood management, water level monitoring, agricultural water discharge, and water pollution management. We evaluated these MLLMs on hydrology-specific tasks, testing their response generation and real-time suitability in complex real-world scenarios. Prompts were designed to enhance the models’ visual inference capabilities and contextual comprehension from images. Our findings reveal that GPT-4 Vision demonstrated exceptional proficiency in interpreting visual data, providing accurate assessments of flood severity and water quality. Additionally, MLLMs showed potential in various hydrological applications, including drought prediction, streamflow forecasting, groundwater management, and wetland conservation. These models can optimize water resource management by predicting rainfall, evaporation rates, and soil moisture levels, thereby promoting sustainable agricultural practices. This research provides valuable insights into the potential applications of advanced AI models in addressing complex hydrological challenges and improving real-time decision-making in water resource management
Turbine-Based Generation in Greenhouse Irrigation Systems
Authors: Rodríguez-Pérez Ángel M. , García-Chica Antonio , Caparros-Mancera Julio J. , Rodríguez César A.
Published: September 2024

This study addresses the need for sustainable and energy-efficient agricultural practices by integrating turbine systems into greenhouse irrigation setups that utilize water from storage basins or ponds. The purpose is to harness excess pressure to generate electricity, enhancing overall system efficiency. This study involves designing a scalable turbine system that adapts to different greenhouse sizes and water pressure conditions. Key methods include a novel 3D design and implementation of a turbine outlet, using CAD modeling and high-precision 3D printing, and the experimental characterization of the system’s power–pressure relationship and pressure losses. Results demonstrate that a single Banki-type turbine generates nearly 12 W at a maximum pressure of 1.4 bar, 0.98 m3/h of flow, pressure 92% loss performance, and 32% efficiency. Scalability tests in the study case reveal that up to eight turbines can be installed in series without dropping below the critical pressure threshold, that is, above 0.6–0.7 bar, the minimum pressure expected for adequate irrigation, and the turbines collectively produce around 60 W, considering the pressure losses with respect to production. These findings confirm the system’s potential to enhance sustainability and energy efficiency in greenhouse operations. This study lays a foundation for future research to optimize 3D-printed components, integrate renewable energy sources, and conduct long-term performance studies, aiming to further improve the system’s applicability and performance in agricultural settings.
Modeling the Impact of Urban and Industrial Pollution on the Quality of Surface Water in Intermittent Rivers in a Semi-Arid Mediterranean Climate
Authors: Bouriqi Abdelillah , Ouazzani Naaila , Deliege Jean-François
Published: September 2024

Ensuring the protection of the aquatic environment and addressing the water scarcity and degradation of water quality in the Mediterranean region pose significant challenges. This study specifically aims to assess the impact of urban and industrial pollution on the ZAT River water quality. The study exploits a combination of field measurements and mathematical simulations using the PEGASE model. The objective is to evaluate how water quality changes throughout the different seasons and to determine whether olive oil factories discharge industrial wastewater into the river. The study reveals that the river water quality remains relatively stable along its course, up to km 64 in winter and km 71.77 in summer, where poor water quality is recorded. This degradation can be attributed to multiple factors. One of these factors is the discharge of industrial wastewater, which accounts for 47% of the COD pollution load. This industrial wastewater is released into the river without treatment during the production period (January–February) and inactivity period (March–May). The combined impact of urban and industrial wastewater is also associated with the decrease in water flow resulting from water withdrawals due to irrigation canals and groundwater recharge, which both contribute to the observed changes in river water quality. Importantly, field measurements combined with results obtained from the calibrated model provide compelling evidence of unauthorized wastewater discharges from the olive oil factories into the river. These results emphasize the need for stricter regulation, such as developing water quality monitoring strategies based on the use of modeling methodologies. They also emphasize the importance of improving wastewater management practices, such as setting up treatment plants for different sources of pollution or developing a co-treatment plant to mitigate the adverse impact of industrial pollution on river water quality.
The Role of the CX3CR1-CX3CL1 Axis in Respiratory Syncytial Virus Infection and the Triggered Immune Response
Authors: Rivas-Fuentes Selma , Salgado-Aguayo Alfonso , Santos-Mendoza Teresa , Sevilla-Reyes Edgar
Published: September 2024

Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and older adults. This virus is responsible for one-third of pneumonia deaths in the pediatric population; however, there are currently only a few effective vaccines. A better understanding of the RSV–host relationship at the molecular level may lead to a more effective management of RSV-related symptoms. The fractalkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and diverse immune cells. RSV G protein binds to the CX3CR1 receptor via a highly conserved amino acid motif (CX3C motif), which is also present in CX3CL1. The CX3CL1-CX3CR1 axis is involved in the activation and infiltration of immune cells into the infected lung. The presence of the RSV G protein alters the natural functions of the CX3CR1-CX3CL1 axis and modifies the host’s immune response, an aspects that need to be considered in the development of an efficient vaccine and specific pharmacological treatment.
Functional Divergence in the Affinity and Stability of Non-Canonical Cysteines and Non-Canonical Disulfide Bonds: Insights from a VHH and VNAR Study
Authors: Xu Mingce , Zhao Zheng , Deng Penghui , Sun Mengsi , Chiu Cookson K. C. , Wu Yujie , Wang Hao , Bi Yunchen
Published: September 2024

Single-domain antibodies, including variable domains of the heavy chains of heavy chain-only antibodies (VHHs) from camelids and variable domains of immunoglobulin new antigen receptors (VNARs) from cartilaginous fish, show the therapeutic potential of targeting antigens in a cytosol reducing environment. A large proportion of single-domain antibodies contain non-canonical cysteines and corresponding non-canonical disulfide bonds situated on the protein surface, rendering them vulnerable to environmental factors. Research on non-canonical disulfide bonds has been limited, with a focus solely on VHHs and utilizing only cysteine mutations rather than the reducing agent treatment. In this study, we examined an anti-lysozyme VNAR and an anti-BC2-tag VHH, including their non-canonical disulfide bond reduced counterparts and non-canonical cysteine mutants. Both the affinity and stability of the VNARs and VHHs decreased in the non-canonical cysteine mutants, whereas the reduced-state samples exhibited decreased thermal stability, with their affinity remaining almost unchanged regardless of the presence of reducing agents. Molecular dynamics simulations suggested that the decrease in affinity of the mutants resulted from increased flexibility of the CDRs, the disappearance of non-canonical cysteine–antigen interactions, and the perturbation of other antigen-interacting residues caused by mutations. These findings highlight the significance of non-canonical cysteines for the affinity of single-domain antibodies and demonstrate that the mutation of non-canonical cysteines is not equivalent to the disruption of non-canonical disulfide bonds with a reducing agent when assessing the function of non-canonical disulfide bonds.
Composite Polycaprolactone/Gelatin Nanofiber Membrane Scaffolds for Mesothelial Cell Culture and Delivery in Mesothelium Repair
Authors: Govindaraju Darshan Tagadur , Kao Hao-Hsi , Chien Yen-Miao , Chen Jyh-Ping
Published: September 2024

To repair damaged mesothelium tissue, which lines internal organs and cavities, a tissue engineering approach with mesothelial cells seeded to a functional nanostructured scaffold is a promising approach. Therefore, this study explored the uses of electrospun nanofiber membrane scaffolds (NMSs) as scaffolds for mesothelial cell culture and transplantation. We fabricated a composite NMS through electrospinning by blending polycaprolactone (PCL) with gelatin. The addition of gelatin enhanced the membrane’s hydrophilicity while maintaining its mechanical strength and promoted cell attachment. The in vitro study demonstrated enhanced adhesion of mesothelial cells to the scaffold with improved morphology and increased phenotypic expression of key marker proteins calretinin and E-cadherin in PCL/gelatin compared to pure PCL NMSs. In vivo studies in rats revealed that only cell-seeded PCL/gelatin NMS constructs fostered mesothelial healing. Implantation of these constructs leads to the regeneration of new mesothelium tissue. The neo-mesothelium is similar to native mesothelium from hematoxylin and eosin (H&E) and immunohistochemical staining. Taken together, the PCL/gelatin NMSs can be a promising scaffold for mesothelial cell attachment, proliferation, and differentiation, and the cell/scaffold construct can be used in therapeutic applications to reconstruct a mesothelium layer.
Fat Mass- and Obesity-Associated Protein (FTO) Promotes the Proliferation of Goat Skeletal Muscle Satellite Cells by Stabilizing DAG1 mRNA in an IGF2BP1-Related m6A Manner
Authors: Yao Jiangzhen , Xu Liang , Zhao Zihao , Dai Dinghui , Zhan Siyuan , Cao Jiaxue , Guo Jiazhong , Zhong Tao , Wang Linjie , Li Li , Zhang Hongping
Published: September 2024

Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats’ longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.
Pathogenic Mechanisms That May Link Periodontal Disease and Type 2 Diabetes Mellitus—The Role of Oxidative Stress
Authors: Mirnic Jelena , Djuric Milanko , Brkic Snezana , Gusic Ivana , Stojilkovic Marija , Tadic Ana , Veljovic Tanja
Published: September 2024

Given the posited role of oxidative stress in the pathogenesis of both periodontitis and type 2 diabetes mellitus (T2DM), it may also serve as a link between these highly prevalent chronic inflammatory diseases. This view is supported by an ample body of evidence indicating that the severity and progression of periodontitis is in part driven by diabetes, while periodontal infection may hinder the attainment of adequate glycemic control in diabetic patients. Thus, this review focuses on the potential synergistic interactions along the oxidative stress–inflammation pathway characterizing both conditions. Because periodontitis and T2DM share the same risk factors and compromise patients’ quality of life, to develop effective strategies for combatting both conditions, their mutual influence needs to be explored.
Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens
Authors: Yao David , Patel Raj S. , Lam Adrien , Glover Quarshie , Srinivasan Cindy , Herchen Alex , Ritchie Bruce , Agrawal Babita
Published: September 2024

There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine. Our study provides evidence for cross-reactive IgG antibodies specific to eight different spike (S) variants. Furthermore, the specificities of these cross-variant IgG antibody titers were associated to some extent with spike S1- and S2-subunit-derived epitopes P1 and P2, respectively. In addition, nucleocapsid (N)- and membrane (M)-specific IgG antibody titers correlated with N- and M-derived epitopes conserved across beta-CoVs, P3–7. This study reveals conserved epitopes of viral antigens, targeted by natural and/or vaccine-induced human immunity, for future designs of next-generation COVID-19 vaccines.
Comparative Transcriptome Analysis of Salt-Tolerant and -Sensitive Soybean Cultivars under Salt Stress
Authors: Cheng Ye , Cheng Xiangqiang , Wei Kai , Wang Yan
Published: September 2024

Soil salinity is a major limiting factor in soybean (Glycine max (L.) Merr.) yield in Xinjiang, China. Therefore, breeding soybean to tolerate highly saline soils is crucial to improve its yield. To explore the molecular mechanisms underlying the response of soybean to salt stress, we performed a comparative transcriptome analysis of root and leaf samples collected from two local soybean cultivars. The salt-tolerant cultivar ‘Xin No. 9’ (X9) showed higher photosynthetic activity than the salt-sensitive cultivar ‘Xinzhen No. 9’ (Z9) under salt stress. In total, we identified 13,180 and 13,758 differential expression genes (DEGs) in X9 and Z9, respectively, of which the number of DEGs identified in roots was much higher than that in leaves. We constructed the co-expression gene modules and conducted Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggested there were distinct differences in the mechanisms of response to salt stress between the two soybean cultivars; i.e., the salt-tolerant cultivar X9 exhibited alterations in fundamental metabolism, whereas the salt-sensitive cultivar Z9 responded to salt stress mainly through the cell cycle. The possible crosstalk among phytohormone signaling, MAPK signaling, phenylpropanoid biosynthesis, starch and sucrose metabolism, and ribosome metabolism may play crucial roles in the response to salt stress in soybean. Our results offered a comprehensive understanding of the genes and pathways involved in the response to salt stress in soybean and provided valuable molecular resources for future functional studies and the breeding of soybean varieties with enhanced tolerance to salinity.
Bisphenol S Promotes the Transfer of Antibiotic Resistance Genes via Transformation
Authors: Zhang Jiayi , Zhu Shuyao , Sun Jingyi , Liu Yuan
Published: September 2024

The antibiotic resistance crisis has seriously jeopardized public health and human safety. As one of the ways of horizontal transfer, transformation enables bacteria to acquire exogenous genes naturally. Bisphenol compounds are now widely used in plastics, food, and beverage packaging, and have become a new environmental pollutant. However, their potential relationship with the spread of antibiotic resistance genes (ARGs) in the environment remains largely unexplored. In this study, we aimed to assess whether the ubiquitous bisphenol S (BPS) could promote the transformation of plasmid-borne ARGs. Using plasmid pUC19 carrying the ampicillin resistance gene as an extracellular ARG and model microorganism E. coli DH5α as the recipient, we established a transformation system. Transformation assays revealed that environmentally relevant concentrations of BPS (0.1–10 μg/mL) markedly enhanced the transformation frequency of plasmid-borne ARGs into E. coli DH5α up to 2.02-fold. Fluorescent probes and transcript-level analyses suggest that BPS stimulated increased reactive oxygen species (ROS) production, activated the SOS response, induced membrane damage, and increased membrane fluidity, which weakened the barrier for plasmid transfer, allowing foreign DNA to be more easily absorbed. Moreover, BPS stimulates ATP supply by activating the tricarboxylic acid (TCA) cycle, which promotes flagellar motility and expands the search for foreign DNA. Overall, these findings provide important insight into the role of bisphenol compounds in facilitating the horizontal spread of ARGs and emphasize the need to monitor the residues of these environmental contaminants.
Risk Assessment of Fenpropathrin: Cause Hepatotoxicity and Nephrotoxicity in Common Carp (Cyprinus carpio L.)
Authors: Zhu Gongming , Liu Zhihui , Wang Hao , Mou Shaoyu , Li Yuanyuan , Ma Junguo , Li Xiaoyu
Published: September 2024

The synthetic pyrethroid pesticide fenpropathrin (FEN) is extensively used worldwide and has frequently been detected in biota and the environment, whilst the negative effects and toxicological mechanisms of FEN on non-target organisms are still unknown. In the present study, healthy immature common carp were treated with FEN (0.45 and 1.35 μg/L) for a duration of 14 days, and the negative impacts and possible mechanisms of FEN on fish were investigated. Biochemical analyses results showed that FEN exposure altered the levels of glucose (GLU), total cholesterol (T-CHO), triglyceride (TG), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) in carp serum, and caused histological injury of the liver and kidney, indicating that FEN may cause hepatotoxicity and nephrotoxicity in carp. In addition, FEN also altered the activities of superoxide dismutase (SOD) and catalase (CAT) in carp serum, upregulated the levels of reactive oxygen species (ROS), and elevated the levels of malondialdehyde (MDA) in the liver and kidney. Meanwhile, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were also upregulated, indicating that oxidative stress and inflammatory reaction may be involved in the hepatotoxicity and nephrotoxicity caused by FEN. Furthermore, RNA-seq analysis results revealed that FEN treatment induced a diverse array of transcriptional changes in the liver and kidney and downregulated differentially expressed genes (DEGs) were concentrated in multiple pathways, especially cell cycle and DNA replication, suggesting that FEN may induce cell cycle arrest of hepatocytes and renal cells, subsequently inducing hepatotoxicity and nephrotoxicity. Overall, the present study enhances our comprehension of the toxic effects of FEN and provides empirical evidence to support the risk assessment of FEN for non-target organisms.
The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism—An Unconventional Ally in Cancer Treatment
Authors: Ung Johnson , Kassai Miki , Tan Su-Fern , Loughran Thomas P. , Feith David J. , Cabot Myles C.
Published: September 2024

The tumor-suppressor sphingolipid ceramide is recognized as a key participant in the cytotoxic mechanism of action of many types of chemotherapy drugs, including anthracyclines, Vinca alkaloids, the podophyllotoxin etoposide, taxanes, and the platinum drug oxaliplatin. These drugs can activate de novo synthesis of ceramide or stimulate the production of ceramide via sphingomyelinases to limit cancer cell survival. On the contrary, dysfunctional sphingolipid metabolism, a prominent factor in cancer survival and therapy resistance, blunts the anticancer properties of ceramide-orchestrated cell death pathways, especially apoptosis. Although P-glycoprotein (P-gp) is famous for its role in chemotherapy resistance, herein, we propose alternate interpretations and discuss the capacity of this multidrug transporter as a “ceramide neutralizer”, an unwelcome event, highlighting yet another facet of P-gp’s versatility in drug resistance. We introduce sphingolipid metabolism and its dysfunctional regulation in cancer, present a summary of factors that contribute to chemotherapy resistance, explain how P-gp “neutralizes” ceramide by hastening its glycosylation, and consider therapeutic applications of the P-gp-ceramide connection in the treatment of cancer.
Renal Cell Carcinoma Discrimination through Attenuated Total Reflection Fourier Transform Infrared Spectroscopy of Dried Human Urine and Machine Learning Techniques
Authors: Buhas Bogdan Adrian , Muntean Lucia Ana-Maria , Ploussard Guillaume , Feciche Bogdan Ovidiu , Andras Iulia , Toma Valentin , Maghiar Teodor Andrei , Crișan Nicolae , Știufiuc Rareș-Ionuț , Lucaciu Constantin Mihai
Published: September 2024

Renal cell carcinoma (RCC) is the sixth most common cancer in men and is often asymptomatic, leading to incidental detection in advanced disease stages that are associated with aggressive histology and poorer outcomes. Various cancer biomarkers are found in urine samples from patients with RCC. In this study, we propose to investigate the use of Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) on dried urine samples for distinguishing RCC. We analyzed dried urine samples from 49 patients with RCC, confirmed by histopathology, and 39 healthy donors using ATR-FTIR spectroscopy. The vibrational bands of the dried urine were identified by comparing them with spectra from dried artificial urine, individual urine components, and dried artificial urine spiked with urine components. Urea dominated all spectra, but smaller intensity peaks, corresponding to creatinine, phosphate, and uric acid, were also identified. Statistically significant differences between the FTIR spectra of the two groups were obtained only for creatinine, with lower intensities for RCC cases. The discrimination of RCC was performed through Principal Component Analysis combined with Linear Discriminant Analysis (PCA–LDA) and Support Vector Machine (SVM). Using PCA–LDA, we achieved a higher discrimination accuracy (82%) (using only six Principal Components to avoid overfitting), as compared to SVM (76%). Our results demonstrate the potential of urine ATR-FTIR combined with machine learning techniques for RCC discrimination. However, further studies, especially of other urological diseases, must validate this approach.