bluuebunny/crossref_metadata_2025 huggingface dataset:
A Data Reconciliation-Based Method for Performance Estimation of Entrained-Flow Pulverized Coal Gasification
Authors: Zhang Yan , Yue Kai , Yuan Chang , Xiang Jiahao
Published: February 2025

Accurate performance estimation of the entrained-flow pulverized coal gasification unit is essential for production scheduling and process optimization, but these are often hindered by inaccurate or insufficient measurements in the industrial system. This paper proposes a data reconciliation-based method to address this challenge. The thermodynamic equilibrium model is employed as constraints of the gasification and quench processes, and the Particle Swarm Optimization (PSO) algorithm is applied for parameter estimation. Measured data under stable and variable operating conditions are reconciled, detecting and eliminating a 12% error in syngas flow rate at the scrubber outlet, thereby improving gasification performance accuracy. Two characteristic models concerning carbon conversion rate and the flow rate of reacted quench water are derived from the reconciled results. By combining these models with thermodynamic equilibrium models, the modified R2 of offline predicted syngas flow rate exceeds 0.92, and those of syngas compositions reach 0.72–0.85. Additionally, an Artificial Neural Network (ANN) model, trained on reconciled and predicted data, is proposed for real-time performance estimation. The ANN model calculates performance metrics within 10 s and achieves R2 values above 0.95 for most parameters. This method can be integrated into control systems and serves as a valuable tool for gasification process monitoring and optimization.
Numerical Analysis of Diesel Engine Combustion and Performance with Single-Component Surrogate Fuel
Authors: Pranta Mehedi Hassan , Cho Haeng Muk
Published: February 2025

Compression ignition engines are widely recognized for their reliability and efficiency, remaining essential for transportation and power generation despite the transition toward sustainable energy solutions. This study employs ANSYS Forte to analyze the combustion and performance characteristics of a direct-injection, single-cylinder, four-stroke engine fueled with an n-heptane-based diesel surrogate. The investigation considers varying SOI timings (−32.5°, −27.5°, −22.5°, and −17.5° BTDC) and EGR rates (0%, 15%, 30%, 45%, and 60%). The simulation incorporates the RNG k-ε turbulence model, the power-law combustion model, and the KH-RT spray breakup model. The results indicate that the optimal peak pressure and temperature occur at an SOI of −22.5° BTDC with 0% EGR. Advancing SOI enhances oxidation, reducing NOx and CO emissions but increasing UHC due to delayed fuel–air mixing. Higher EGR rates lower in-cylinder pressure, temperature, HRR, and NOx emissions while elevating CO and UHC levels due to oxygen depletion and incomplete combustion. These findings highlight the trade-offs between combustion efficiency and emissions, emphasizing the need for optimized SOI and EGR strategies to achieve balanced engine performance.
Design and Performance Study of Large-Angle Inlet Guide Vane with Contraction Channels
Authors: Sai Qingyi , Qin Bo , Zhao Jin , Meng Lingshu
Published: February 2025

Negative inlet pre-swirl has been identified as a potentially effective method to improve the theoretical work that has been performed. However, it should be noted that a large negative inlet swirl may adversely affect the pressure ratio of the compressor due to the different centrifugal forces generated by the movement of the airflow within the large-angle pre-swirl guide vane flow channel. In order to achieve a large inlet negative pre-swirl, a new guide vane with a contraction channel is proposed for a 40° pre-swirl angle fan. This contraction guide vane is of the tandem type, and it includes a first-stage enlarged guide vane and a second-stage contraction guide vane channel. Comprehensive CFD numerical simulations and experimental studies have been conducted to analyze the key design parameters, and the total pressure loss and efficiency of the new guide vanes were analyzed and compared under various operating conditions. It was found that this new guide vane can significantly reduce the total pressure loss coefficients. Compared with the conventional guide vanes, the inlet velocity distribution is more uniform development of inlet velocities, and a significant reduction in flow separation is found for this new guide vane. The guide vane with a ring width ratio of 1.5 reduced 53.11% of the total pressure loss coefficient. In addition, the efficiency of the fan has been shown to increase by more than 2.29% under various operating conditions, due to the improved internal flow of the fan under large flow conditions, under all operating conditions, with an overall improvement in the total pressure ratio of about 5%.
Operation Control Design of Grid-Connected Photovoltaic and Fuel Cell/Supercapacitor Hybrid Energy Storage System
Authors: Zhou Ke , Wen Xiankui , He Mingjun , Tang Qian , Tan Junfeng
Published: February 2025

In order to smooth the fluctuation of photovoltaic (PV) power affected by irradiation conditions, weaken the frequent disturbance to the distribution network, and, thus, enhance its acceptance to PV, a fuel cell/supercapacitor hybrid energy storage device (FSHESS) is configured on the DC side of a grid-connected PV system, which is combined with the PV unit to form a hybrid PV power generation system, i.e., the PV-FSHESS. Based on the analysis of the electrical characteristics of the FC and the SC, an improved low-pass filtering method based on rules and considering the state of charge constraint of the SC is proposed for the power allocation of the FSHESS. With respect to the problem of DC-bus voltage stabilization, a modified variable speed integral nonlinear PI controller is presented for the purpose of overcoming the following disadvantages: (i) the ordinary PI controller cannot adaptively adjust the cumulative speed of the integral term in line with the deviation, which may cause large overshoot and oscillation; and (ii) the conventional variable speed integral controller has more parameters, which increases the difficulty of parameter tuning. The simulation verification is carried out under different operating conditions of PV output power and load demands, and the results prove the effectiveness of the proposed control scheme.
Experimental Analysis of Vacuum Solar Collectors as an Auxiliary Heating Source for Residential Buildings
Authors: Urbaniak Rafał , Ciupek Bartosz , Grobelny Paweł
Published: February 2025

This study presents an experimental analysis of two vacuum solar air collectors designed for residential heating applications. The research was conducted from November 2022 to April 2024 in real operating conditions. This study focused on assessing the thermal performance, energy efficiency, and feasibility of integrating these systems into hybrid heating solutions. The first collector (Solar Dragon 2022) utilized five vacuum tubes and achieved a total thermal energy output of 397.67 kWh over five months, with a peak thermal power of 0.55 kW. The second system (Solar Dragon 2023), equipped with 24 vacuum tubes, demonstrated a significantly higher performance, generating 911.69 kWh over the same period, with a peak thermal power of 1.8 kW. The study also identified challenges related to airflow distribution and excessive outlet air temperatures, reaching up to 84 °C in the modified system, which could negatively impact indoor comfort. The findings highlight the potential of vacuum solar collectors as an auxiliary heating source, particularly in transitional seasons, while emphasizing the need for optimized airflow control and thermal regulation strategies to enhance their practical application.
Transient Frequency Modeling and Characteristic Analysis of Virtual Synchronous Generator
Authors: Su Zhou , Yang Guoqing , Yao Lixiao
Published: February 2025

The large-scale integration of renewable energy into power systems significantly alters their operational characteristics, reducing system inertia and posing challenges to transient frequency stability. Virtual synchronous generator (VSG) technology offers a solution by enhancing system inertia and improving transient frequency stability. To quantitatively analyze the transient characteristics of VSGs and optimize their control strategies, it is crucial to develop a comprehensive transient frequency model. This paper establishes a transient frequency model for VSGs, incorporating their inertial response, primary frequency regulation, and secondary frequency regulation. A MATLAB/Simulink-based (version R2021b) simulation model is constructed to validate the analytical model. Additionally, the impact of various control parameters on VSG transient frequency is examined, providing valuable insights and guidance for maintaining system frequency stability.
The Role and Impact of Sporting Mega-Events in the Context of Soft Power
Authors: Alshikhy Tariq , O’Sullivan Helen , Polkinghorne Martyn , Gennings Ellie
Published: February 2025

“Mega-events” are characterized as expansive cultural gatherings. They include both sporting and commercial elements, and they collectively exert significant global influence and appeal. “Sporting mega-events”, in particular, represent a central component of such gatherings and serve as key expressions of national soft power on the world stage. “Soft power” encompasses practices and behaviors aimed at cultivating relational capital, and according to Nye, effective soft power strategies rely on streamlined processes and a blend of tangible and intangible resources to communicate influence, negotiate power, and achieve desired outcomes. In the context of sporting mega-events, soft power operates through cooperation and the alignment of shared interests rather than coercion, thereby appealing to international audiences, and governments therefore strategically host these events to enhance their global standing and secure diplomatic and economic benefits.
Where is the Eastern Larch Beetle? An Exploration of Different Detection Methods in Northern Wisconsin
Authors: Francart Holly , McGraw Amanda M. , Knight Joseph , Windmuller-Campione Marcella A.
Published: February 2025

Foresters and natural resource managers are increasingly exploring opportunities for the early detection of emerging forest health concerns. One of these emerging concerns is the eastern larch beetle (ELB, Dendroctonus simplex LeConte), a native insect of tamarack (Larix laricina (Du Roi) K., Koch). Historically, the ELB attacked only dead or dying trees, but with climate change, it is now becoming a damaging disturbance agent that affects healthy trees as well. This shift creates a need to evaluate the methods used to detect and quantify the impacted areas. In northern Wisconsin, USA, 50 tamarack stands or aerial detection polygons were surveyed in the field during the 2023 growing season to explore different detection tools for ELBs. We visited 20 polygons identified by aerial sketch map surveys as having ELB mortality, 20 tamarack stands identified by the Astrape satellite imagery algorithm as disturbed, and 10 randomly selected stands from the Wisconsin forest inventory database (WisFIRs) for landscape-level context. For each of the detection methods and the Random stands, information on species composition, mortality, signs of ELB, invasive species, and water presence was quantified. ELBs were common across the landscape, but were not always associated with high levels of mortality. While overstory tree mortality was frequently observed in both aerial sketch map surveys and Astrape, it was not always linked to tamarack mortality. Current methods of detection may need to be re-evaluated in this environment. Tamarack stands in northern Wisconsin were highly heterogeneous in species, which is likely contributing to the difficulties in identifying both tamarack mortality and tamarack mortality specifically caused by ELBs across the two detection methods. Given the evolving impacts of climate change and the shifting dynamics between forests and insects, it is essential to evaluate and innovate detection methods to manage these ecosystems effectively.
Gamitest: A Game-like Online Student Assessment System
Authors: Swacha Jakub , Kulpa Artur
Published: February 2025

The widespread availability of mobile devices has led to the emergence of multiple gamified web and mobile applications for online assessment of students during classes. Their common weak side is that they focus mostly on positive reinforcement, without exploiting the pedagogical potential of loss and failure experience; thus, they are far from an actual game-like experience. In this paper, we present Gamitest, a course-subject-agnostic web application for student assessment that features an original game-like scheme to improve students’ perception of engagement and fun, as well as to reduce their examination stress. The results of the survey-based evaluation of the tool indicate that its design goals have been met and allow us to recommend it for consideration in various forms of student assessment, as well as provide grounds for future work on analyzing the tool’s effects on learning.
Neutral Delayed Fractional Models in Financial Time Series: Insights into Borsa Istanbul Sectors Affected by the Kahramanmaraş Earthquake
Authors: Akgüller Ömer , Balcı Mehmet Ali , Batrancea Larissa Margareta , Altan Koç Dilara , Nichita Anca
Published: February 2025

This study examines the impact of the Kahramanmaraş Earthquake on four key sectors of Borsa Istanbul: Basic Metal, Insurance, Non-Metallic Mineral Products, and Wholesale and Retail Trade using neutral delayed fractional differential equations. Employing the Chebyshev collocation method, we numerically solved the neutral delayed fractional differential equations with initial conditions scaled by each sector’s log difference standard deviation to accurately reflect market volatility. Fractional orders were derived from the Hurst exponent, and time delays were identified using average mutual information, autocorrelation function, and partial autocorrelation function methods. The results reveal significant changes post-earthquake, including reduced market persistence and increased volatility in the Basic Metal and Insurance sectors, contrasted by enhanced stability in the Non-Metallic Mineral Products sector. Neutral delayed fractional differential equations demonstrated superior performance over traditional models by effectively capturing memory and delay effects. This work underscores the efficacy of neutral delayed fractional differential equations in modeling financial resilience amid external shocks.
Ultrasound-Enhanced Gelation of Stimuli-Responsive and Biocompatible Phenylalanine-Derived Hydrogels
Authors: Buxaderas Eduardo , Moglie Yanina , Figueroa Aarón Baz , Alegre-Requena Juan V. , Grijalvo Santiago , Saldías César , Herrera Raquel P. , Marqués-López Eugenia , Díaz Díaz David
Published: February 2025

Stimuli-responsive materials, particularly supramolecular hydrogels, exhibit a dynamic adaptability to external factors such as pH and ultrasound. Among these, phenylalanine (Phe)-derived hydrogels are promising due to their biocompatibility, biodegradability, and tunable properties, making them ideal for biomedical applications. This study explores the effects of pH and ultrasound on the gelation properties of N-substituted Phe derivatives, with a primary focus on the role of ultrasound in optimizing the gelation process. A series of N-substituted Phe derivatives were synthesized via reductive amination and hydrolysis. Hydrogel formation was possible with two of these compounds, namely G1 and G2, using the following two methods: heating–cooling (H–C) and heating–ultrasound–cooling (H–US–C). The critical gelation concentration (CGC), gelation kinetics, thermal stability (Tgel), and viscoelastic properties were assessed. Morphological and cytotoxicity analyses were performed to confirm the suitability of these gels for biomedical applications. Both G1 and G2 derivatives demonstrated enhanced gelation under the H–US–C protocol compared to H–C, with notable reductions in CGC (up to 47%) and gelation time (by over 90%). Ultrasound-induced gels led to an improved network density and stability, while maintaining thermal reversibility and mechanical properties comparable to those of hydrogels formed without ultrasound. Cytotoxicity studies confirmed a high biocompatibility, with cell viability rates above 95% across the tested concentrations. Given the similar rheological and morphological properties of the hydrogels regardless of the preparation method, drug release experiments were performed with representative gel samples and demonstrated the efficient encapsulation and controlled release of 5-fluorouracil and methotrexate from the hydrogels, supporting their potential as pH-responsive drug delivery platforms. This study highlights the role of ultrasound as a powerful tool for accelerating and optimizing the gelation process of supramolecular hydrogels, which is particularly relevant for applications requiring rapid gel formation. The developed Phe-based hydrogels also demonstrate promising characteristics as drug delivery systems.
Metabolomic and Transcriptomic Analyses of Flavonoid Biosynthesis in Dendrobium devonianum Flowers
Authors: Li Yue , Wu Yawen , Pu Ran , Li Xuejiao , Bai Tian , Li Nengbo , Zhou Ying , Zhang Jingli
Published: February 2025

Background: Dendrobium devonianum is a traditional Chinese medicinal herb with notable ornamental and medicinal value. Methods: In this study, transcriptomic and metabolomic approaches were employed to investigate gene expression and secondary metabolite changes during four developmental stages of D. devonianum flowers. Results: Metabolomic analysis identified 1186 distinct metabolites, with flavonoid compounds being the most abundant category (213 types). Transcriptomic analysis revealed 31 differentially expressed genes associated with flavonoid biosynthesis and flavonoid and flavonol biosynthesis pathways. Among these, key genes regulating flavonol synthesis, including F3H (Unigene0077194) and FLS (Unigene0062137), exhibited high expression levels in the early developmental stage (S1). Conclusions: Flavonoids serve as the major active components in D. devonianum flowers, exhibiting a wide range of pharmacological properties. This study provides valuable insights into the molecular mechanisms driving flavonoid accumulation in D. devonianum, offering a foundation for further functional studies and applications in ornamental and medicinal plant research.
Exploring Ecological and Conventional Farming Practice on Plum Orchards: Its Impact on Fruit Quality
Authors: Cara Irina Gabriela , Rusu Mariana , Filip Manuela , Țopa Denis , Jităreanu Gerard
Published: February 2025

Fruit quality is crucial for nutrition and human health and requires emergent cautions in contemporary agricultural techniques. Ecological farming might not be as successful as conventional management systems; however, it may yield superior quality fruits due to reduced protection treatments. This research aimed to investigate the influence of ecological and conventional farming practices on the physicochemical properties (fruit color, weight, firmness, titratable acidity, total sugar, vitamin C), antioxidant activities, bioactive compounds (total polyphenols, anthocyanin and flavonoids), macroelements composition (N, P, K), and heavy metal concentration (Zn, Cd, Pb and Cu) of the Centenar plum variety soil system under the environmental conditions of Romania. The analysis revealed that ecological farming practice increased the total polyphenol content (3.26–4.52 mg GAE/g of dw) and antioxidant activity (19.53–21.70 µm Trolox/g of dw); however, ecological farming practice supported healthy soils and maintained or built soil organic carbon more substantially (56.68 Mg C ha−1). Moreover, more consistent and vigorous fruit colors were provided by ecological farming practices where small fruits (41 g) were obtained compared to conventional farming (44 g). Among the metal content in plum fruit, Cu had the highest level (0.74–1.07 mg kg−1), while Cd had the lowest (0.003–0.007 mg kg−1). The potential health risk of heavy metals accumulation in orchard soils and their transfer in fruit (MTF) was also analyzed. Total carcinogenic risk (TCR) values for all metals were less than 1 (≤1), which is considered to be a safe level with no concern for human health. These results show that plum fruits under ecological farming received improved nutritional values and correspond to sustainable food production through limiting resource competition.
Deep-Learning-Based Evaluation of Rooftop Photovoltaic Deployment in Tianjin, China
Authors: Shan Mei , Xu Yue , Sun Yun , Wang Yuan , Li Lei , Qiao Zhi , Zuo Jian
Published: February 2025

Rooftop photovoltaics (RPVs) are crucial in addressing energy shortages and environmental concerns caused by fossil fuel combustion. To promote the optimal deployment of RPVs in Tianjin, a region with abundant solar resources and dense buildings, this study proposes a framework that integrates building vector data with a deep learning model to extract currently installed RPVs from remote sensing images, and further estimate the development potential of RPVs. A total of 86,363 RPV polygons were extracted, covering an area of 10.34 km2. More than 70% of these RPVs are concentrated on large and low-rise buildings, and a similar proportion is found in industrial buildings, as these buildings offer favorable installation conditions. Combining solar radiation and construction land development planning, we further determined the potential deployment zone of RPVs covering about 13% of the Tianjin’s land area, which represents 31.31 TWh per year of power generation potential. In the future, it is recommended to prioritize RPV installation on large and low-rise buildings or industrial buildings in the potential deployment zone, which could provide higher power generation and contribute significantly to environmental emission reduction goals. The proposed research framework can also be applied to other cities.
Evaluation Methods for the Human–Land Coupling Coordination Relationship in a Metro Station Area: A Case Study of Chengdu Metro Line 1
Authors: Qiu Zhiyue , Wen Shirui , Yuan Hong , Liu Ziyi , Wei Yao , Yanling Siqi , Dai Runlong , Li Xiang , Gu Yuxin
Published: February 2025

At present, more than 200 cities in the world have developed metro systems. Under the agglomeration effect of traffic nodes, rapid population agglomeration and land development and utilization have formed around metro stations in cities. However, there is still the problem of uncoordinated development in each station area along the metro, so it is urgent to build an evaluation method of the coupling and coordination relationship between people and land to study the laws of population activities, industrial agglomeration, traffic resources, and other aspects in the metro station area and analyze its rationality and matching. In this study, Chengdu, the central city in the west of China, is selected as an example, and Metro Line 1, which has the longest history and is the most mature development in the city, is taken as an example. Starting from the coupling and coordination relationship between the human activity demand and metro resource supply, the evaluation indicator system of the coupling and coordination relationship between people and land in the station area of Chengdu Metro Line 1 is constructed. By collecting multi-source data, the coupling coordination degree model (CCDM) is used to quantitatively evaluate the human–land coupling coordination relationship in the station area. Then, the gray relational analysis (GRA) combined with the spatial distribution characteristics are used to analyze the characteristics and influencing factors of the coupling and coordination relationship, and it is concluded that the station area of Chengdu Metro Line 1 presents a circular and multi-center coupling and horizontal coordination spatial structure. Among them, the degrees of the population concentration and activity intensity, the levels of economic and industrial development, the level of service support, and the degree of contact with surrounding areas have great influences on the coupling and coordination levels of the station area. Finally, some improvement strategies are put forward, such as optimizing the network layout, building multi-level centers, strengthening functional connections, and enhancing the development intensity. This study provides a new method for the study of the coordinated development of metro station areas and has practical significance for evaluating the construction and development statuses of metro station areas, guiding the planning of metro stations, and formulating regional development strategies of metro stations.
Novel Circulating Biomarkers in Aortic Valve Stenosis
Authors: Ong Joy Yi-Shan , Tan Sarah Ming Li , Koh Angela S. , Kong William , Sia Ching Hui , Yeo Tiong Cheng , Quek Swee Chye , Poh Kian Keong
Published: February 2025

The underlying pathophysiology of aortic stenosis and factors affecting its clinical progression remain poorly understood. Apart from B-type natriuretic peptide (BNP), novel and emerging biomarkers have been described in association with aortic stenosis, emphasising the potential for these biomarkers to illuminate on yet unknown mechanisms of its pathogenesis. In this review, we aimed to summarise what is known about aortic stenosis biomarkers, highlight the emerging ones, and provide a roadmap for translating these insights into clinical applications. Among the biomarkers studied, lipoprotein(a) [Lp(a)] has emerged as the most promising for risk stratification. Elevated Lp(a) levels are often associated with more rapid aortic stenosis progression. This detrimental effect is attributed to its role in promoting valve calcification. While other emerging biomarkers such as matrix metalloproteinases, monocytes, and metabolites show promises, their specific roles in aortic stenosis pathophysiology remain less clear. This may be due to their relatively recent discovery. Ongoing research aims to elucidate their mechanisms of action.
MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137
Authors: Wang Hefeng , Wu Jianhua , Fang Ying , Li Quhuan
Published: February 2025

CD137 is a prominent costimulatory molecule of the tumor necrosis factor (TNF) receptor superfamily that activates T cells through a complex bidirectional signaling process involving CD137L. The clinical value of immunotherapies underscores the potential of CD137L/CD137 as an effective target for boosting antitumor immune responses; however, the intricate mechanisms governing these interactions have not been fully elucidated. Herein, we constructed various oligomeric states of CD137L (monomeric, dimeric, and trimeric CD137L) and explored their interactions with CD137 using molecular dynamics simulations. Our findings revealed that trimeric CD137L exhibits higher thermal stability but reduced binding affinity for CD137 compared with the dimer form, with the A’B’ loop of CD137L playing a critical role in both structural stability and promoting CD137 interactions. Notably, the formation of hexameric structures enhanced the binding affinity and stability. This study provides valuable insights into the CD137L/CD137 bidirectional signaling mechanisms, which may inform the design of next-generation CD137 agonists. Ultimately, these advancements may improve cancer immunotherapy strategies, aiming to enhance therapeutic outcomes for patients through more effective and targeted therapies.
A Two-Hour Fetal Glucagon Infusion Stimulates Hepatic Catabolism of Amino Acids in Fetal Sheep
Authors: Tanner Amelia R. , Cilvik Sarah N. , Nguyen Marjorie A. , Dobrinskikh Evgenia , Anthony Russell V. , Wesolowski Stephanie R. , Rozance Paul J.
Published: February 2025

Postnatally, glucagon acutely lowers plasma amino acid (AA) concentrations by stimulating hepatic AA catabolism, but its fetal actions remain unclear. This study tested whether a 2 h fetal glucagon infusion would stimulate hepatic AA catabolism and inhibit placental AA transfer. Late-gestation pregnant sheep (0.9 gestation) underwent surgical, vascular catheterization and received fetal glucagon (n = 8) or vehicle infusions (n = 8) in a crossover design with a 48 h washout period. Nutrient uptake and utilization were assessed during each infusion, and fetal liver and placental tissue were collected post-infusion under hyperglucagonemic (n = 4) or vehicle (n = 4) conditions. Glucagon receptor was identified in fetal hepatocyte and trophoblast cells. Glucagon reduced fetal plasma AA concentrations by 20% (p = 0.0103) and increased plasma glucose by 47% (p = 0.0152), leading to a three-fold rise in fetal plasma insulin (p = 0.0459). Hepatic gene expression associated with AA catabolism and gluconeogenesis increased (p < 0.0500) following glucagon infusion, and hepatic metabolomic analysis showed enrichment in AA metabolism pathways. However, placental AA transfer was unaffected by 2 h fetal glucagon infusions. In conclusion, a 2 h glucagon infusion stimulates hepatic glucose production and enhances AA catabolism in the fetal liver, lowering plasma AA concentrations. The primary acute effects of fetal glucagon are hepatic, as placental AA transfer is unchanged.
The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer
Authors: Mladenov Mitko , Sazdova Iliyana , Hadzi-Petrushev Nikola , Konakchieva Rossitza , Gagov Hristo
Published: February 2025

Reductive stress (RS), characterized by excessive accumulation of reducing equivalents such as NADH and NADPH, is emerging as a key factor in metabolic disorders and cancer. While oxidative stress (OS) has been widely studied, RS and its complex interplay with endocrine regulation remain less understood. This review explores molecular circuits of bidirectional crosstalk between metabolic hormones and RS, focusing on their role in diabetes, obesity, cardiovascular diseases, and cancer. RS disrupts insulin secretion and signaling, exacerbates metabolic inflammation, and contributes to adipose tissue dysfunction, ultimately promoting insulin resistance. In cardiovascular diseases, RS alters vascular smooth muscle cell function and myocardial metabolism, influencing ischemia-reperfusion injury outcomes. In cancer, RS plays a dual role: it enhances tumor survival by buffering OS and promoting metabolic reprogramming, yet excessive RS can trigger proteotoxicity and mitochondrial dysfunction, leading to apoptosis. Recent studies have identified RS-targeting strategies, including redox-modulating therapies, nanomedicine, and drug repurposing, offering potential for novel treatments. However, challenges remain, particularly in distinguishing physiological RS from pathological conditions and in overcoming therapy-induced resistance. Future research should focus on developing selective RS biomarkers, optimizing therapeutic interventions, and exploring the role of RS in immune and endocrine regulation.
Mitochondrial Dysfunction in Cardiovascular Diseases
Authors: Yang Han-Mo
Published: February 2025

Mitochondrial dysfunction is increasingly recognized as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Mitochondria, known as the powerhouses of the cell, play a vital role in maintaining cardiac energy homeostasis, regulating reactive oxygen species (ROS) production and controlling cell death pathways. Dysregulated mitochondrial function results in impaired adenosine triphosphate (ATP) production, excessive ROS generation, and activation of apoptotic and necrotic pathways, collectively driving the progression of CVDs. This review provides a detailed examination of the molecular mechanisms underlying mitochondrial dysfunction in CVDs, including mutations in mitochondrial DNA (mtDNA), defects in oxidative phosphorylation (OXPHOS), and alterations in mitochondrial dynamics (fusion, fission, and mitophagy). Additionally, the role of mitochondrial dysfunction in specific cardiovascular conditions is explored, highlighting its impact on endothelial dysfunction, myocardial remodeling, and arrhythmias. Emerging therapeutic strategies targeting mitochondrial dysfunction, such as mitochondrial antioxidants, metabolic modulators, and gene therapy, are also discussed. By synthesizing recent advances in mitochondrial biology and cardiovascular research, this review aims to enhance understanding of the role of mitochondria in CVDs and identify potential therapeutic targets to improve cardiovascular outcomes.
Hypoxia Modulates Transmembrane Prostatic Acid Phosphatase (TM-PAP) in MCF-7 Breast Cancer Cells
Authors: Lacerda-Abreu Marco Antonio , Carvalho-Kelly Luiz Fernando , Meyer-Fernandes José Roberto
Published: February 2025

In MCF-7 breast cancer cells, transmembrane prostatic acid phosphatase (TM-PAP) plays a critical role in tumor progression, particularly under hypoxic conditions. In this study, the impact of hypoxia on ectophosphatase activity in MCF-7 cells was examined, and the underlying biological mechanisms that influence the breast cancer microenvironment were explored. Compared with normoxic cells, hypoxic cells presented significant reductions in ectophosphatase activity, indicating that hypoxia altered dephosphorylation processes critical for tumor growth and metastasis. Specific decreases in the hydrolysis of substrates, such as p-nitrophenylphosphate (pNPP) and adenosine monophosphate (AMP), were observed under hypoxic conditions, suggesting that hypoxia impaired TM-PAP activity. Further investigation revealed that hypoxia induced an increase in the concentration of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), which inhibited ectophosphatase activity. This effect was reversed by the introduction of ROS scavengers. Additionally, hypoxia activated protein kinase C (PKC), further modulating ectophosphatase activity in MCF-7 cells. Collectively, these findings enhanced the understanding of the mechanisms through which hypoxia could influence enzyme activity associated with cancer progression and provide valuable insights into the development of targeted therapeutic strategies.
PCSK9 Enhances Cardiac Fibrogenesis via the Activation of Toll-like Receptor and NLRP3 Inflammasome Signaling
Authors: Chung Cheng-Chih , Kao Yu-Hsun , Chen Yao-Chang , Lin Yung-Kuo , Higa Satoshi , Hsu Kai-Cheng , Chen Yi-Jen
Published: February 2025

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel target for reducing low-density lipoprotein cholesterol. PCSK9 activates the atherosclerosis process through pro-inflammation signaling. Furthermore, the serum level of PCSK9 is positively correlated with mortality in patients with heart failure (HF). Cardiac fibrosis plays a crucial role in the pathophysiology of HF. In this study, we intended to examine whether PCSK9 can increase fibroblast activities and explore what its underlying mechanisms are. Migration, proliferation analyses, and Western blotting were used on human cardiac fibroblasts with and without PCSK9. Alirocumab (a PCSK9 inhibitor, 10 mg/kg/week intra-peritoneally for 28 consecutive days) was treated in isoproterenol (100 mg/kg, subcutaneous injection)-induced HF rats. PCSK9 (50, 100 ng/mL) increased proliferation, myofibroblast differentiation capability, and collagen type I production. Compared with control cells, PCSK9 (100 ng/mL)-treated cardiac fibroblasts showed higher nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), interleukin (IL)-1, myofibroblast differentiation, and collagen production capabilities, which were attenuated by MCC950 (an NLRP3 inhibitor, 100 μmol/L). PCSK9 upregulated Myd88 and NF-κB signaling, which were reduced by TAK242 (a toll-like receptor (TLR) 4 inhibitor, 10 μmol/L). Moreover, alirocumab significantly improved left ventricular systolic function and attenuated fibrosis in HF rats. In conclusion, PCSK9 upregulates NLRP3 signaling and the profibrotic activities of cardiac fibroblasts through the activation of TLR4/Myd88/NF-κB signaling.
Unraveling the Mechanism of the Endophytic Bacterial Strain Pseudomonas oryzihabitans GDW1 in Enhancing Tomato Plant Growth Through Modulation of the Host Transcriptome and Bacteriome
Authors: Ahmed Waqar , Wang Yan , Ji Wenxia , Liu Songsong , Zhou Shun , Pan Jidong , Li Zhiguang , Wang Fusheng , Wang Xinrong
Published: February 2025

Endophytic Pseudomonas species from agricultural crops have been extensively studied for their plant-growth-promoting (PGP) potential, but little is known about their PGP potential when isolated from perennial trees. This study investigated the plant-growth-promoting (PGP) potential of an endophyte, Pseudomonas oryzihabitans GDW1, isolated from a healthy pine tree by taking tomato as a host plant. We employed multiomics approaches (transcriptome and bacteriome analyses) to elucidate the underlying PGP mechanisms of GDW1. The results of greenhouse experiments revealed that the application of GDW1 significantly improved tomato plant growth, increasing shoot length, root length, fresh weight, and biomass accumulation by up to 44%, 38%, 54%, and 59%, respectively, compared with control. Transcriptomic analysis revealed 1158 differentially expressed genes significantly enriched in the plant hormone signaling (auxin, gibberellin, and cytokinin) and stress response (plant–pathogen interaction, MAPK signaling pathway-plant, and phenylpropanoid biosynthesis) pathways. Protein–protein interaction network analysis revealed nine hub genes (MAPK10, ARF19-1, SlCKX1, GA2ox2, PAL5, SlWRKY37, GH3.6, XTH3, and NML1) related to stress tolerance, hormone control, and plant defense. Analysis of the tomato root bacteriome through 16S rRNA gene amplicon sequencing revealed that GDW1 inoculation dramatically altered the root bacterial community structure, enhancing the diversity and abundance of beneficial taxa (Proteobacteria and Bacteroidota). Co-occurrence network analysis showed a complex bacterial network in treated plants, suggesting increasingly intricate microbial relationships and improved nutrient absorption. Additionally, FAPROTAX and PICRUSt2 functional prediction analyses suggested the role of GDW1 in nitrogen cycling, organic matter degradation, plant growth promotion, and stress resistance. In conclusion, this study provides novel insights into the symbiotic relationship between P. oryzihabitans GDW1 and tomato plants, highlighting its potential as a biofertilizer for sustainable agriculture and a means of reducing the reliance on agrochemicals.
Genome-Wide Exploration and Characterization of the TCP Gene Family’s Expression Patterns in Response to Abiotic Stresses in Siberian Wildrye (Elymus sibiricus L.)
Authors: Liu Tianqi , Peng Jinghan , Dong Zhixiao , Liu Yingjie , Wu Jiqiang , Xiong Yanli , Zhang Changbing , Yan Lijun , Yu Qingqing , You Minghong , Ma Xiao , Lei Xiong
Published: February 2025

Siberian wildrye (Elymus sibiricus L.), a model Elymus Gramineae plant, has high eco-economic value but limited seed and forage yield. TCP transcription factors are widely regarded as influencing yield and quality and being crucial for growth and development; still, this gene family in Siberian wildrye remains unexplored. Therefore, this study looked at the Siberian wildrye TCP gene family’s reaction to several abiotic stresses, its expression pattern, and its potential evolutionary path. Fifty-four members of the EsTCP gene family were discovered. There are two major subfamilies based on the phylogenetic tree: 27 of Class I (PCF) and 27 of Class II (12 CIN-type and 15 TB1/CYC-type). Gene structure, conserved motif, and sequence alignment analyses further validated this classification. Cis-elements found in the promoter region of EsTCPs are associated with lots of plant hormones and stress-related reactions, covering drought induction and cold tolerance. EsCYC5, EsCYC6, and EsCYC7 may regulate tillering and lateral branch development. EsPCF10’s relative expression was significant under five stresses. Additionally, eight EsTCP genes are potential miR319 targets. These findings highlight the critical significance of the TCP gene family in Siberian wildrye, laying the groundwork for understanding the function of the EsTCP protein in abiotic stress studies and high-yield breeding.
Correction: Peretz, E.; Musa, S. Design, Synthesis, and Characterization of Novel Cannabidiol-Based Derivatives with Potent Antioxidant Activities. Int. J. Mol. Sci. 2024, 25, 9579
Authors: Peretz Eliav , Musa Sanaa
Published: February 2025

In the original publication, there was a mistake in Figure 5D as published [...]
Thaumatin-like Gene TLP1b Confers to Seed Oil Content and Resistance to Sclerotinia sclerotiorum in Arabidopsis
Authors: Liao Jinghang , Qi Shucheng , Huang Hong , Liao Hongmei , Cui Yixin , Liu Zhi , Qian Wei , Dong Hongli
Published: February 2025

The synergistic optimization of yield and abiotic/biotic resistance is of great significance in plant breeding. However, the genomic mechanisms underlying the selection for environmental adaptation and yield-related traits remain poorly understood. In this study, we identified a thaumatin-like protein (TLP), AtTLP1b, which was shown to pleiotropically regulate seed oil content and resistance to Sclerotinia sclerotiorum by gene knockout and overexpressing experiments in Arabidopsis. The oil composition oleic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3) and eicosenoic acid (C20:1) were altered significantly in overexpressing and knockout lines. RNA-seq analysis revealed that overexpression of AtTLP1b significantly downregulated the expression levels of genes involved in wax, suberin synthesis, oxylipin metabolism and plant–pathogen interaction. Furthermore, more than half of the genes involved in the circadian rhythm–plant pathway were differentially expressed in the overexpressing lines. We propose that AtTLP1b primarily inhibits fatty acid synthesis and plant immune responses via the circadian rhythm–plant pathway. Our findings suggest that AtTLP1b plays a vital role in simultaneous improvement of seed oil content and resistance to S. sclerotiorum and provides a valuable resource for molecular breeding.
Molecular Pathways, Neural Circuits and Emerging Therapies for Self-Injurious Behaviour
Authors: Zhang Kristina , Ibrahim George M. , Venetucci Gouveia Flavia
Published: February 2025

Nonsuicidal self-injurious behaviour (SIB) is a debilitating manifestation of physical aggression commonly observed across neurodevelopmental, psychiatric, and genetic disorders. This behaviour arises from a multifactorial aetiology involving genetic predispositions, epigenetic modifications, neurotransmitter dysregulation, and environmental stressors. Dysregulation in dopaminergic, serotonergic, glutamatergic, and GABAergic systems has been implicated in the pathophysiology of SIB, alongside structural and functional abnormalities within fronto-limbic-striatal circuits. These disruptions impair key processes, such as emotional regulation, reward processing, and behavioural inhibition, contributing to the emergence and reinforcement of SIB. Advances in preclinical research using genetic, lesion-based, pharmacological, and environmental animal models have been instrumental in elucidating the molecular and neurocircuitry underpinnings of SIB. Emerging neuromodulation therapies targeting critical nodes within the fronto-limbic-striatal network, particularly deep brain stimulation, have shown promise in treating severe, refractory SIB and improving quality of life. This review integrates current evidence from clinical studies, molecular research, and preclinical models to provide a comprehensive overview of the pathophysiology of SIB and therapeutic approaches. By focusing on the molecular mechanisms and neural circuits underlying SIB, we highlight the translational potential of emerging pharmacological and neuromodulatory therapies. A deeper understanding of these pathways will pave the way for precision-based interventions, bridging the gap between molecular research and clinical applications in SIB and related conditions.
TANK-Binding Kinase 1 in the Pathogenesis and Treatment of Inflammation-Related Diseases
Authors: Hui Lu , Chen Xiaolin , Huang Mengke , Jiang Yongmei , Liu Ting
Published: February 2025

TANK-binding kinase 1 (TBK1) is a key signaling kinase involved in innate immune and inflammatory responses. TBK1 drives immune cells to participate in the inflammatory response by activating the NF-κB and interferon regulatory factor signaling pathways in immune cells, promoting the expression of pro-inflammatory genes, and regulating immune cell function. Thus, it plays a crucial role in initiating a signaling cascade that establishes an inflammatory environment. In inflammation-related diseases, TBK1 acts as a bridge linking inflammation to immunity, metabolism, or tumorigenesis, playing an important role in the pathogenesis of immune-mediated inflammatory diseases, metabolic, inflammatory syndromes, and inflammation-associated cancers by regulating the activation of inflammatory pathways and the production of inflammatory cytokines in cells. In this review, we focused on the mechanisms of TBK1 in immune cells and inflammatory-related diseases, providing new insights for further studies targeting TBK1 as a potential treatment for inflammation-related diseases. Thus, optimizing and investigating highly selective cell-specific TBK1 inhibitors is important for their application in these diseases.
The Zebrafish Model in Animal and Human Health Research
Authors: Szychlinska Marta Anna , Marino Gammazza Antonella
Published: February 2025

The present Special Issue aims to highlight several advantages of the zebrafish model in various fields of biomedical and ecotoxicological research [...]
Biomarkers in Hereditary Spastic Paraplegias
Authors: Panza Emanuele , Orlacchio Antonio
Published: February 2025

Hereditary spastic paraplegias (HSPs) represent a group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs, with no specific treatment available for patients. At the same time, the molecular diagnosis is complicated by the high genetic heterogeneity of this group of diseases, and it can be challenging due to overlapping clinical features with other conditions. Reliable biomarkers could play a fundamental role in diagnosis, prognosis, and therapeutic interventions for HSPs. For this reason, it is necessary to increase the search for biomarkers that can be used to rapidly classify HSPs, follow the natural history of the conditions, and monitor disease correction therapies. This article provides an overview of the current understanding of biomarkers in HSPs, including genetic, biochemical, and clinical biomarkers and new cell imaging-based approaches. In this manuscript, we aim to provide an overview of the current situation in HSP biomarkers, emphasizing the limitations and the necessity of conducting more studies in this field.