bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth Dynamics and Nutrient Removal from Biogas Slurry Using Water Hyacinth
Authors: Koley Apurba , GhoshThakur Richik , Das Kaushik , Gupta Nitu , Banerjee Aishiki , Show Binoy Kumar , Ghosh Anudeb , Chaudhury Shibani , Hazra Amit Kumar , Nahar Gaurav , Ross Andrew B. , Balachandran Srinivasan
Published: May 2024

Aquatic macrophytes, notably the invasive water hyacinth, exhibit proficiency in nutrient removal from polluted water bodies, rendering them appealing for water remediation applications. This study investigates the potential of water hyacinth in phytoremediation, focusing on the effect of using nutrient-rich biogas slurry mixed with water in varying concentrations, i.e., 16.6, 33, 66.6, 100, and 133 mg/L for the investigation. The physiochemical properties of the liquid biogas slurry were evaluated before and after treatment with water hyacinth over eight weeks, with continuous monitoring of nutrient reduction rates. Results showcased substantial average reductions of nitrogen, phosphorus, and potassium, with a relative growth rate of 5.55%. The treatment also decreased pH, total dissolved solids, hardness, and chemical oxygen demand. The theoretical BMP of water hyacinth was determined using Buswell’s equation. Water hyacinth grown in the concentration of the biogas slurry exhibited the highest methane yield at 199 mL CH4/gm VS, along with the highest relative growth rate. This study used experimental data to create a mathematical model that describes how the relative growth of water hyacinth depends on the number of days and biogas slurry concentration (C). The model’s quality and effectiveness were evaluated using the goodness of fit (R2) and observable approaches. The polynomial model, referred to as Poly model 1, 2, is the best fit for describing the relationship between the growth percentage of water hyacinth, days, and nutrient solution concentration. In this model, C has a polynomial degree of one (normalized mean of 69.84 ± 43.54), while D has a degree of two (normalized mean of 30 ± 21.65).
Creative Learning for Sustainability in a World of AI: Action, Mindset, Values
Authors: Henriksen Danah , Mishra Punya , Stern Rachel
Published: May 2024

In an era marked by unprecedented global challenges, including environmental degradation, social inequalities, and the rapid evolution of technology, the need for innovative educational approaches is critical. This conceptual paper explores the intersection of sustainability, creativity, and technology for education, focusing on artificial intelligence (AI) as an example. We propose a framework that synthesizes sustainability principles and creative pedagogies, detailing its components to guide the integration of AI into sustainability education. The paper illustrates how blending creative pedagogies with the notion of sustainability as a frame of mind offers a framework that allows teachers to support creative learning and problem solving, with and through technology. Using the example of AI technology, we illustrate the potential benefits and inherent challenges of integrating new technologies into education. Generative AI is a cogent example, as it presents unique opportunities for personalizing learning and engaging students in creative problem solving around sustainability issues. However, it also introduces significant environmental and ethical concerns to navigate. Exploring the balance between technological innovation and sustainability imperatives, this paper outlines a framework for incorporating technology into education that promotes environmental care with creative exploration. Through a synthesis of sustainability principles and creative pedagogies, we highlight the benefits and challenges of using AI in education, offering strategic insights to leverage technology for a sustainable and just future.
The Impact of Rural–Urban Student Mobility on the Efficiency of Resource Allocation in China’s Rural Households: Optimization or Distortion?
Authors: Wang Ruonan , Li Xiaoyan , Wei Jinyang , Zheng Fengtian
Published: May 2024

The impact of rural-urban student mobility on the efficiency of resource allocation in China’s rural households is crucial for refining policies related to rural migrant settlement and the balanced allocation of urban and rural educational resources. Drawing on theoretical insights, this study employs a mixed methods approach—primarily qualitative, with quantitative support—to empirically test the impact of rural-urban student mobility on the resource allocation efficiency of rural households in China. Utilizing micro-survey data from China Family Panel Studies (CFPS), this study applies ordinary least squares (OLS) models, propensity score matching difference-in-differences (PSM-DID) models, and endogenous switching regression (ESR) models to ascertain the direction of this impact. Furthermore, this study incorporates in-depth interview data gathered from field research in D County to explore the dynamic mechanisms of resource allocation adjustments within these households. The results show that rural-urban student mobility significantly reduces the efficiency of labor resource allocation and agricultural production in China’s rural households. The impact is heterogeneous across different groups, most negatively affecting households with limited labor resources, lower educational levels, lower incomes, more productive fixed assets, and less self-owned land. Mobility leads to suboptimal occupational choices, resulting in decreased labor resource efficiency. Additionally, it distorts agricultural production by leading to labor loss, reduced investments in agricultural productivity, and misaligned land allocation decisions.
Investigating the Correlation between Air Pollution and Housing Prices in Seoul, South Korea: Application of Explainable Artificial Intelligence in Random Forest Machine Learning
Authors: Ko Dongwon , Park Seunghoon
Published: May 2024

South Korea’s Particulate Matter (PM) concentration is among the highest among Organization for Economic Cooperation and Development (OECD) member countries. However, many studies in South Korea primarily focus on housing characteristics and the physical built environment when estimating apartment prices, often neglecting environmental factors. This study investigated factors influencing apartment prices using transaction data for Seoul apartments provided by the Ministry of Land, Infrastructure, and Transport (MOLIT) in 2019. For this purpose, the study compared and analyzed a traditional hedonic price model with a machine learning-based random forest model. The main findings are as follows: First, the evaluation results of the traditional hedonic price model and the machine learning-based random forest model indicated that the random forest model was found to be more suitable for predicting apartment prices. Second, an importance analysis using Explainable Artificial Intelligence (XAI) showed that PM is more important in determining apartment prices than access to education and bus stops, which were considered in this study. Finally, the study found that areas with higher concentrations of PM tend to have higher apartment prices. Therefore, when proposing policies to stabilize apartment prices, it is essential to consider environmental factors. Furthermore, it is necessary to devise measures such as assigning PM labels to apartments during the home purchasing process, enabling buyers to consider PM and obtain relevant information accordingly.
Green Finance Advancement and Its Impact on Urban Haze Pollution in China: Evidence from 283 Cities
Authors: Qiang Yichen , Tang Yao , Wang Chen
Published: May 2024

This study selects the entropy method to measure the comprehensive index of green finance and 2011–2020 panel data covering 283 cities in China; describes spatial and temporal evolution, the migration of the centre of gravity, and discrete trends in green finance and urban haze pollution; and empirically examines the effect of green finance on urban haze pollution using static and dynamic spatial Durbin models. The study revealed that Chinese urban haze pollution significantly decreased during the sample period and that the hotspot emission area shifted to the northeast. Green finance experienced significant advancement, transitioning from a lower stage to a higher stage and becoming more geographically focused. Green finance mainly suppresses urban haze pollution through spatial spillover effects, and such spatial spillover effects change from positive to negative over time. Regarding regional heterogeneity, the effect on the western region is positive, the effects on the central and eastern regions are negative, and there is a spatial spillover effect “from promotion to inhibition” in the eastern region. Due to the heterogeneity in resource endowments, green finance in nonresource-based cities has a greater impact on haze pollution than does green finance in other cities, and in the long term, it has a significant inhibitory effect on haze pollution. This study reveals the effect of green finance on urban haze pollution from a dynamic perspective and, in doing so, it not only provides a new path for joint governance of haze pollution between cities but also provides more accurate guidance for the government to formulate policies for different regions and regions with different resource endowments.
Log-Linear Model and Delivery Load Analysis for Improvements in Water Quality through TMDL in the Gyeongan Stream Watershed, Republic of Korea
Authors: Im Jihyeok , Woo Donghyeon , Kong Dongsoo
Published: May 2024

The effectiveness of implementing the total maximum daily load (TMDL) in the Gyeongan stream watershed was evaluated to assess its impact on water quality. The relationships between water quality and flow rate and load and water quality were reinterpreted using a log-linear model and the delivery load, respectively. To estimate annual water quality trends and analyze the effects of water quality improvement in each parameter, an improved multivariable log-linear model addressing the limitations of the traditional L-Q equation was applied to analyze the relationship between water quality and flow rate, excluding the effects of flow rate and seasonality. The effect of total phosphorus (T-P) was particularly prominent. A new delivery load was developed and applied to address the limitations of the original unit-based delivery load. Evaluations showed that water quality continuously improved across all parameters, and all methods (excluding the influence of flow rate on water quality fluctuations) were highly effective in estimating water quality changes attributable to anthropogenic pollution sources. The analysis of pollutant contributions revealed that managing point sources is necessary for controlling the biochemical oxygen demand and total nitrogen, while point and non-point sources require T-P management. Future policy development should consider this when formulating management strategies.
Exploring the Landscape of Media Campaigns That Encourage or Discourage Sustainable Diet Transitions for Americans, 1917–2023: A Systematic Scoping Review
Authors: Consavage Stanley Katherine , Leary Nicole , Holz Adrienne , Hedrick Valisa E. , Serrano Elena L. , Kraak Vivica I.
Published: May 2024

United States (U.S.) and global experts recommend that populations reduce red and processed meat (RPM) intake and transition to plant-rich, sustainable diets to support human and planetary health. A systematic scoping review was conducted to identify the landscape of media campaigns that promote plant-rich dietary patterns, traditional plant proteins, and novel plant-based meat alternatives (PBMA) and that encourage or discourage RPM products to Americans. Of 8321 records screened from four electronic databases, 103 records were included, along with 62 records from gray literature sources. Across 84 media campaigns (1917–2023) identified, corporate marketing campaigns (58.6%) were most prevalent compared to public information (13.8%), corporate sustainability (12.6%), countermarketing (5.7%), social marketing (4.6%), and public policy (4.6%) campaigns. Findings indicate that long-running corporate RPM campaigns, many with U.S. government oversight, dominated the landscape for decades, running alongside traditional plant protein campaigns. Novel PBMA campaigns emerged in the past decade. Many civil society campaigns promoted plant-rich dietary patterns, but few utilized social norm or behavior change theory, and only the Meatless Monday campaign was evaluated. The U.S. government, academia, businesses, and civil society should commit more resources to and evaluate the impact of media campaigns that support a sustainable diet transition for Americans, restrict and regulate the use of misinformation in media campaigns, and prioritize support for plant-based proteins and plant-rich dietary patterns.
Spatiotemporal Evolution and Future of Carbon Storage in Resource-Based Chinese Province: A Case Study from Shanxi Using PLUS–InVEST Model Prediction
Authors: Jiao Yuhua , Wang Yuhui , Tu Chenghong , Hou Xuenan , Lyu Chunjuan , Fan Xiang , Xia Lu
Published: May 2024

Resource exploitation markedly alters land use and ecological carbon storage, posing risks to carbon sinks and food security. This study analyzes land-use change from 1990 to 2020 in the resource-based province of Shanxi, China. By introducing a mineral resource driver, the PLUS model was used to predict four scenarios: natural development (ND), cropland protection (CP), ecological protection (EP), and dual protection of ecology and cropland (DP). The spatial and temporal evolutions of carbon storage were then analyzed using the InVEST model. Forests were predominantly distributed in mountainous areas, with croplands in southerly and central flat areas, construction lands in and around cities, and mining lands sporadically distributed across Shanxi. From 1990 to 2020, croplands and grasslands decreased, while forest, construction, and mining lands increased. Carbon storage decreased continuously, with a total loss of 15.1 × 106 t. High-value carbon storage areas were in the Lüliang, Taihang, and Taiyue Mountains, and low-value areas were in the more populous central and southern regions. Carbon storage was predicted to decline by 2035 under the ND and CP scenarios and to exceed that of 2020 under the EP and DP scenarios. The DP scenario projected an increase of 4.93 × 106 t in carbon storage by 2035. The DP scenario realizes the protection of carbon sinks in resource-based areas and maintains food security, providing a theoretical reference for achieving carbon neutrality and high-quality sustainable development in Shanxi Province.
Research on the Public’s Intention to Use Shared Autonomous Vehicles: Based on Social Media Data Mining and Questionnaire Survey
Authors: Liao Yang , Guo Hanying , Shi Hongguo
Published: May 2024

While the emergence of shared autonomous vehicles can be an effective solution to improve transport issues and achieve sustainable development, the benefits associated with shared autonomous vehicles can only be realized when the public intends to use them. Therefore, it is necessary to conduct an in-depth study on the public’s intention to use shared autonomous vehicles and identify the key influencing factors. This study mined social media data to obtain real public perceptions. A qualitative exploratory analysis was used to identify thematic variables regarding social media data on shared autonomous vehicles, from which a research model of the public’s intention to use SAVs was proposed. Then, a questionnaire survey was conducted, and the structural equation model and Bayesian network were used to analyze the questionnaire data quantitatively. The findings reveal how perceived risk, social information, trust, perceived usefulness, and personality traits affect the public’s intention to use shared autonomous vehicles, and how to enhance the public’s intention to use them. This study will enrich the research on traveler psychology in the context of intelligent travel and provide theoretical basis and decision support for future policies to promote shared autonomous vehicles.
Summary of Research on Highway Bridge Vehicle Force Identification
Authors: Yang Bing-Chen , Zhao Yu , Yao Tian-Yun , Zhou Yong-Jun , Jia Meng-Yi , Hu Hai-Yang , Xiao Chang-Chun
Published: May 2024

Vehicle force identification is one of the core technical problems to be solved urgently in the management of transportation infrastructure, and it has also been a research hotspot in recent years. To promote the application of vehicle force identification technology on bridges and explore its development direction, the development status of indirect vehicle force identification methods based on bridge response is reviewed during this study. The basic theories of two major methods, including bridge weigh-in-motion (BWIM) and moving force identification (MFI), are described in detail in this study, and then, the key technical principles of bridge force identification are revealed. Secondly, the development status of BWIM in recent years is reviewed from three aspects, including test accuracy, applicability and test efficiency. Combined with a variety of theories, the current status of MFI is analyzed from the establishment of the solution to the equation. Finally, the development direction of an artificial neural network and machine vision technology are prospected in this study. The BP neural network has good self-learning ability and self-adaptive ability, but the algorithm needs to be improved. The identification method based on machine vision represents the current development direction in vehicle force identification, with great potential.
The Influencing Mechanism of Managerial Myopic Behavior on Enterprise Sustainable Development Performance: Evidence Based on Listed Companies in China
Authors: Cui Yuzhen , Zhu Shunlin
Published: May 2024

Corporate sustainability is a key concern in today’s world. This research examines the relationship between managerial myopic behavior and corporate sustainability performance in Chinese A-share listed companies from 2013 to 2022. Based on behavioral finance theory and time orientation theory, our research provides novel insights into how time preference in managerial decisions significantly affects corporate sustainable development. We also investigate how myopic behavior by managers can adversely affect a company’s sustainable development performance. Using a robust dataset, we describe the mechanisms by which managers’ myopic behavior affects sustainability performance, especially in two aspects: financialization of assets and green innovation capability. The results of our research show the following: (1) managers’ myopic behavior adversely affects corporate sustainability performance; (2) asset financialization and green innovation capability play mediating roles; and (3) unlike the findings of the existing research, this study found that the linear moderating effect of media attention plays a significant “inverted U-shaped” moderating role in the relationship between the two influences.
Household Food Waste in Morocco: An Exploratory Survey in the Province of Kenitra
Authors: Belfakira Chaimaa , Hindi Zakia , Lafram Amina , Bikri Samir , Benayad Asmaa , El Bilali Hamid , Gjedsted Bügel Susanne , Średnicka-Tober Dominika , Pugliese Patrizia , Strassner Carola , Rossi Laura , Stefanovic Lilliana , Aboussaleh Youssef
Published: May 2024

The data from the United Nations Food Waste Index 2021 suggest that food losses and waste represent a pressing challenge, even in developing countries. This study investigates food waste in Morocco, specifically focusing on Kenitra province (northwestern Morocco). It quantifies the food waste types and quantities in Kenitra households and explores the underlying causes. Conducted in 2022, the research involved 442 respondents aged 18 and above, utilizing both face-to-face and online surveys. The findings reveal bread as the most wasted item, with minimal waste of meat and cereals. On average, households discard 361 g of bread per week, 98 g of fresh produce, and 9 g of cheese. The primary causes of food waste are difficulties in reusing small leftovers (32%), followed by challenges in meal preparation with available ingredients (34%). This study underscores the urgent need for targeted interventions to address food waste effectively in Kenitra. By shedding light on waste dynamics and causes, it contributes to understanding this critical issue and offers valuable insights for policymakers and stakeholders working to implement strategies for reducing food waste and promoting sustainable consumption practices.
Thinking of Green, Low Carbon, and Energy-Saving Designs Based on the Variable Ventilation of Natatoriums: Taking the Jiading Natatorium of Tongji University as an Example
Authors: Qian Feng , Shi Zedao , Yang Li
Published: May 2024

With the increasing demand for sports activities, sports architecture is flourishing. Creating a comfortable and healthy fitness environment while reducing energy consumption has become a focus for architects. Taking the Jiading Natatorium at Tongji University in Shanghai as an example, this study researched green energy in the variable ventilation of sports venues. The Autodesk Ecotect Analysis 2011 was used to conduct computational fluid dynamics (CFD) simulation analyses on four scenarios of opening and closing the swimming pool’s roof, with ventilation velocity as the primary evaluation indicator to assess the ventilation environment of each scenario. The relationship between the opening ratio of the roof and the ventilation environment of sports buildings was explored. The results showed that when the opening ratio is 37.5%, it achieves good ventilation effectiveness and avoids excessive wind pressure. The study also summarized six common forms of opening and closing roof structures and compared the differences in wind environments of different roof forms. The results indicated that the shape and opening ratio of the roof has a decisive impact on the distribution of indoor wind speed in buildings. Six optimal opening ratios for different roof forms in summer and suitable site conditions were summarized, providing a reference for the design and selection of swimming pool roofs. Furthermore, the wind speed distribution of different roof types showed a trend of gradually becoming uniform with the increase in opening area. However, the position of the wind speed peak is related to the form and size of the roof opening. This research provides valuable references for the low carbon and energy-efficient design of future swimming pool sports buildings.
Effects of Rainfall Intensity and Slope on Infiltration Rate, Soil Losses, Runoff and Nitrogen Leaching from Different Nitrogen Sources with a Rainfall Simulator
Authors: Simelane Mzwakhile Petros Zakhe , Soundy Puffy , Maboko Martin Makgose
Published: May 2024

The combined effects of slope gradient, rainfall intensity, and nitrogen fertilizer source on infiltration, runoff, soil loss, and nitrogen (N) leaching in agricultural areas are not thoroughly understood, despite their critical importance in sustainable agriculture. Previous studies have focused on these factors individually, leaving a significant gap in knowledge regarding their synergistic impact. Investigating the interplay between slope gradients, rainfall intensities, and N fertilizer sources is vital to developing effective soil and water conservation strategies and implementing sustainable agricultural practices. This study is comprised of two experiments. Experiment 1 was designed as a 3 × 2 × 3 factorial arrangement, incorporating three levels of rainfall intensity (RI) (45, 70, and 100 mm/h), two slope gradients (5 and 8°), and three soil types (sandy loam, silt loam, and clay loam), aimed at assessing runoff, infiltration, and soil loss. Experiment 2, laid out as 3 × 2 × 3 × 3 factorial, expanded on this, adding N fertilizer source (urea, CaCN2, and limestone ammonium nitrate (LAN) at 130 kg/ha N) and assessing N leaching alongside the previous metrics. Both experiments used a rotating disc rainfall simulator and were replicated four times. Results revealed that steeper slopes (8°) led to increased runoff and soil loss, impeding infiltration, while gentler slopes (5°) facilitated greater infiltration and minimized soil loss. Rainfall intensity played a significant role, with 70 mm/h/5° combinations promoting higher infiltration rates (48.14 mm/h) and 100 mm/h/8° resulting in lower rates (37.07 mm/h for sandy loam and silt loam, 26.09 mm/h for clay loam). Nitrogen leaching varied based on N source; urea at 130 kg/ha N led to higher losses (7.2% in sandy loam, 6.9% in silt loam, 6.5% in clay loam), followed by LAN (6.9% in sandy loam, 6.7% in silt loam, 6.3% in clay loam) while CaCN2 at the same rate resulted in lower N losses (6.4% in sandy soil, 4.4% in silt loam, 4.2% in clay soil). This research highlights the critical need to consider both slope gradient and rainfall intensity in conjunction with appropriate nitrogen fertilizer sources when developing strategies to mitigate soil erosion and nutrient loss in agricultural settings.
Numerical Study on Aerodynamic Noise Reduction in Passenger Car with Fender Shape Optimization
Authors: Jiao Dongqi , Zhou Haichao , Huang Tinghui , Zhang Wei
Published: May 2024

Despite the rapid development of vehicle intelligent technology, the aerodynamic noise problem of internal combustion engine vehicles and pure electric vehicles at high speed has always been a growing problem. In this study, the effects of the car body fender shape on the aerodynamic noises of the rearview mirror and wheel region were investigated, and a noise reduction method was also proposed by optimizing the fender shape. To realize the parametric modeling of the fender, five positional variables were selected to define the fender configuration; the free-form deformation (FFD) method was used to establish the response fender model according the DOE schemes, and computational fluid dynamics (CFD) simulations are used to obtain the noise results. Then, with the help of the radial basis function (RBF) model and the adaptive simulated annealing (ASA) algorithm, the aerodynamic shape of the fender was optimized to reduce aerodynamic noise. Comparative analysis was then employed to assess flow field characteristics of the optimized model against the original model and elucidate the fender configuration’s contribution to aerodynamic noise reduction and its realization mechanism.
Non-Fasting Plasma Triglycerides Are Positively Associated with Diabetes Mortality in a Representative US Adult Population
Authors: Wang Yutang , Fang Yan , Zhang Xiulin , Wu Na-Qiong
Published: May 2024

This study aimed to investigate whether non-fasting plasma triglycerides were associated with diabetes mortality. It included 7312 US adult participants. Diabetes mortality data were obtained via the linkage to National Death Index (NDI) records. Hazard ratios of non-fasting plasma triglycerides for diabetes mortality were assessed using Cox proportional hazards models, adjusting for age, gender, ethnicity, obesity, poverty–income ratio, education levels, physical activity, alcohol consumption, cigarette smoking status, survey period, hypercholesterolemia, hypertension, diabetes, and family history of diabetes. Among these participants, 1180 had diabetes. A total of 420 diabetes-caused deaths were recorded during a mean follow-up of 16.8 years. A 1-natural-log-unit increase in non-fasting plasma triglycerides was associated with a 41% higher diabetes mortality risk (hazard ratio, 1.41; 95% confidence interval, 1.19–1.67). Participants with non-fasting plasma triglycerides in the highest quintile, versus those in the lowest quintile, had a 141% higher diabetes mortality risk (hazard ratio, 2.41; 95% confidence interval, 1.46–3.97). The positive association of non-fasting plasma triglycerides with diabetes mortality was independent of diabetes status at the baseline. In conclusion, this study demonstrated that non-fasting plasma triglycerides were positively associated with diabetes mortality, independent of diabetes status at baseline. Non-fasting triglycerides may be a therapeutic target for diabetes-related complications.
GC/MS-Based Metabolomic Analysis of A549 Cells Exposed to Emerging Organophosphate Flame Retardants
Authors: Sun Mengyao , Chang Xiao , Gao Ying , Zou Sisi , Wang Shaomin , Liu Hongmin
Published: May 2024

Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological studies of the above eOPFRs, especially their information on the perturbation of cellular metabolism, which is, thus far, marginally understood. Our research initially assessed the cytotoxicity of eOPFRs, which include compounds like cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), triallyl phosphate (TAP), and pentaerythritol phosphate alcohol (PEPA). This evaluation was conducted using the methyl thiazolyl tetrazolium (MTT) assay. Subsequently, we utilized a gas chromatography/mass spectrometry (GC/MS)-based metabolomic approach to investigate the metabolic disruptions induced by these four eOPFRs in A549 cells. The MTT results showed that, at high concentrations of 1 mM, their cytotoxicity was ranked as CDP > TAP > RDP > PEPA. In addition, metabolic studies at low concentrations of 10 μM showed that the metabolic interference of CDP, TAP, and PEPA focuses on oxidative stress, amino acid metabolism, and energy metabolism, while RDP mainly affects energy metabolism—galactose metabolism and gluconeogenesis. Therefore, from the perspective of cytotoxicity and metabolic analysis, RDP may be a more promising alternative. Our experiments provide important insights into the possible metabolic effects of potential toxic substances and complement the evidence on the human health risks of eOPFRs.
Machine Learning to Predict Drug-Induced Liver Injury and Its Validation on Failed Drug Candidates in Development
Authors: Mostafa Fahad , Howle Victoria , Chen Minjun
Published: May 2024

Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and procedures to enhance the accuracy of DILI risk prediction for drug candidates under development. In this study, we leveraged a large human dataset to develop machine learning models for assessing DILI risk. The performance of these prediction models was rigorously evaluated using a 10-fold cross-validation approach and an external test set. Notably, the random forest (RF) and multilayer perceptron (MLP) models emerged as the most effective in predicting DILI. During cross-validation, RF achieved an average prediction accuracy of 0.631, while MLP achieved the highest Matthews Correlation Coefficient (MCC) of 0.245. To validate the models externally, we applied them to a set of drug candidates that had failed in clinical development due to hepatotoxicity. Both RF and MLP accurately predicted the toxic drug candidates in this external validation. Our findings suggest that in silico machine learning approaches hold promise for identifying DILI liabilities associated with drug candidates during development.
The Effects of Aflatoxin B1 on Liver Cholestasis and Its Nutritional Regulation in Ducks
Authors: Yu Aimei , Wang Huanbin , Cheng Qianhui , Rajput Shahid Ali , Qi Desheng
Published: May 2024

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB1. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB1 group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB1 caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB1 upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB1 negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB1-induced cholestasis.
Clostridioides difficile Toxins: Host Cell Interactions and Their Role in Disease Pathogenesis
Authors: Alam Md Zahidul , Madan Rajat
Published: May 2024

Clostridioides difficile, a Gram-positive anaerobic bacterium, is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide. The severity of C. difficile infection (CDI) varies, ranging from mild diarrhea to life-threatening conditions such as pseudomembranous colitis and toxic megacolon. Central to the pathogenesis of the infection are toxins produced by C. difficile, with toxin A (TcdA) and toxin B (TcdB) as the main virulence factors. Additionally, some strains produce a third toxin known as C. difficile transferase (CDT). Toxins damage the colonic epithelium, initiating a cascade of cellular events that lead to inflammation, fluid secretion, and further tissue damage within the colon. Mechanistically, the toxins bind to cell surface receptors, internalize, and then inactivate GTPase proteins, disrupting the organization of the cytoskeleton and affecting various Rho-dependent cellular processes. This results in a loss of epithelial barrier functions and the induction of cell death. The third toxin, CDT, however, functions as a binary actin-ADP-ribosylating toxin, causing actin depolymerization and inducing the formation of microtubule-based protrusions. In this review, we summarize our current understanding of the interaction between C. difficile toxins and host cells, elucidating the functional consequences of their actions. Furthermore, we will outline how this knowledge forms the basis for developing innovative, toxin-based strategies for treating and preventing CDI.
The Equation of State of Novel Double-Field Pure K-Essence for Inflation, Dark Matter and Dark Energy
Authors: Gao Changjun
Published: May 2024

K-essence theories are usually studied in the framework of a single scalar field ϕ. Namely, the Lagrangian of K-essence is the function of the single scalar field ϕ and its covariant derivative. However, in this paper, we explore a double-field pure K-essence, i.e., the corresponding Lagrangian is the function of covariant derivatives of double scalar fields without a dependency on scalar fields themselves. This is why we call it double-field pure K-essence. The novelty of this K-essence is that its Lagrangian contains the quotient term of the kinetic energies from the two scalar fields. This results in the presence of many interesting features; for example, the equation of state can be arbitrarily small and arbitrarily large. In comparison, the range of the equation of state for quintessence is −1 to +1. Interestingly, this novel K-essence can play the role of an inflation field, dark matter, or dark energy by appropriately selecting the expressions of Lagrangian.
A Comprehensive Review of Our Understanding and Challenges of Viral Vaccines against Swine Pathogens
Authors: Kamboj Aman , Dumka Shaurya , Saxena Mumtesh Kumar , Singh Yashpal , Kaur Bani Preet , da Silva Severino Jefferson Ribeiro , Kumar Sachin
Published: May 2024

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines.
Efficient Production of Enterovirus 71 (EV71) Virus-like Particles by Controlling Promoter Strength in Insect Cells
Authors: Kim Hyun-Soo , Moon Hyuk-Jin , Choi Jae-Bang , Han Beom-Ku , Woo Soo
Published: May 2024

This study was conducted to efficiently produce virus-like particles (VLPs) of enterovirus 71 (EV71), a causative virus of hand, foot, and mouth disease (HFMD). The expression level of the P1 precursor, a structural protein of EV71, was modified to increase VLP production, and the optimal expression level and duration of the 3CD protein for P1 cleavage were determined. The expression level and duration of 3CD were controlled by the p10 promoter, which was weakened by repeated burst sequence (BS) applications, as well as the OpIE2 promoter, which was weakened by the insertion of random untranslated region sequences of various lengths. The cleavage and production efficiency of the P1 precursor were compared based on the expression time and level of 3CD, revealing that the p10-BS5 promoter with four repeated BSs was the most effective. When P1 and 3CD were expressed using the hyperexpression vector and the p10-BS5 promoter, high levels of structural protein production and normal HFMD-VLP formation were observed, respectively. This study suggests that the production efficiency of HFMD-VLPs can be significantly enhanced by increasing the expression of the P1 precursor and controlling the amount and duration of 3CD expression.
Intracellular “In Silico Microscopes”—Comprehensive 3D Spatio-Temporal Virus Replication Model Simulations
Authors: Knodel Markus M. , Nägel Arne , Herrmann Eva , Wittum Gabriel
Published: May 2024

Despite their small and simple structure compared with their hosts, virus particles can cause severe harm and even mortality in highly evolved species such as humans. A comprehensive quantitative biophysical understanding of intracellular virus replication mechanisms could aid in preparing for future virus pandemics. By elucidating the relationship between the form and function of intracellular structures from the host cell and viral components, it is possible to identify possible targets for direct antiviral agents and potent vaccines. Biophysical investigations into the spatio-temporal dynamics of intracellular virus replication have thus far been limited. This study introduces a framework to enable simulations of these dynamics using partial differential equation (PDE) models, which are evaluated using advanced numerical mathematical methods on leading supercomputers. In particular, this study presents a model of the replication cycle of a specific RNA virus, the hepatitis C virus. The diffusion–reaction model mimics the interplay of the major components of the viral replication cycle, including non structural viral proteins, viral genomic RNA, and a generic host factor. Technically, surface partial differential equations (sufPDEs) are coupled on the 3D embedded 2D endoplasmic reticulum manifold with partial differential equations (PDEs) in the 3D membranous web and cytosol volume. The membranous web serves as a viral replication factory and is formed on the endoplasmic reticulum after infection and in the presence of nonstructural proteins. The coupled sufPDE/PDE model was evaluated using realistic cell geometries based on experimental data. The simulations incorporate the effects of non structural viral proteins, which are restricted to the endoplasmic reticulum surface, with effects appearing in the volume, such as host factor supply from the cytosol and membranous web dynamics. Because the spatial diffusion properties of genomic viral RNA are not yet fully understood, the model allows for viral RNA movement on the endoplasmic reticulum as well as within the cytosol. Visualizing the simulated intracellular viral replication dynamics provides insights similar to those obtained by microscopy, complementing data from in vitro/in vivo viral replication experiments. The output data demonstrate quantitative consistence with the experimental findings, prompting further advanced experimental studies to validate the model and refine our quantitative biophysical understanding.
Safety and Immunogenicity of the Live Attenuated Varicella Vaccine in Vietnamese Children Aged 12 Months to 12 Years: An Open-Label, Single-Arm Bridging Study
Authors: Hung Pham Van , Giang Le Thi Huong , Toi Phung Lam , Thuc Vu Thi Minh , Anh Bui Dang The , Pho Dinh Cong , Hung Pham Ngoc
Published: May 2024

Objective: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. Methods: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). Results: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. Conclusion: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.
The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines
Authors: Primadharsini Putu Prathiwi , Takahashi Masaharu , Nishizawa Tsutomu , Sato Yukihiro , Nagashima Shigeo , Murata Kazumoto , Okamoto Hiroaki
Published: May 2024

Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3–80.9%). Conversely, it displayed lower similarity (73.3–78.1%) with the HEV-1–5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.
Intranasal Vaccination with a Respiratory-Syncytial-Virus-Based Virus-like Particle Displaying the G Protein Conserved Region Induces Severe Weight Loss and Pathology upon Challenge with Wildtype Respiratory Syncytial Virus
Authors: Terhüja Megolhubino , Siddappa Manjunath , Lamichhane Pramila , Meshram Chetan D. , Snider Timothy A. , Ritchey Jerry W. , Oomens Antonius G. P.
Published: May 2024

Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease worldwide, and a pediatric vaccine is not available. We generated a filamentous RSV-based virus-like particle (VLP) that presents the central conserved region of the attachment protein G. This was achieved by co-expressing the matrix protein, phosphoprotein, nucleoprotein, and a hybrid fusion protein in which the F ectodomain was replaced with the G central region (GCR). The latter is relatively conserved and contains a receptor binding site and hence is a logical vaccine target. The immunogenicity and efficacy of the resulting VLP, termed VLP-GCR, were examined in mice using intranasal application without adjuvant. VLP-GCR induced substantial anti-N antibody levels but very low anti-G antibody levels, even after three vaccinations. In contrast, a VLP presenting prefusion-stabilized fusion (preF) protein instead of GCR induced both high anti-F and anti-nucleoprotein antibody levels, suggesting that our GCR antigen was poorly immunogenic. Challenge of VLP-GCR-vaccinated mice caused increased weight loss and lung pathology, and both VLPs induced mucus in the lungs. Thus, neither VLP is suitable as a vaccine for RSV-naive individuals. However, VLP-preF enhanced the proportion of preF antibodies and could serve as a multi-antigen mucosal booster vaccine in the RSV-experienced population.