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21 pages, 1559 KiB  
Article
Assessing Hydropower Impacts on Flood and Drought Hazards in the Lancang–Mekong River Using CNN-LSTM Machine Learning
by Muzi Zhang, Boying Chi, Hongbin Gu, Jian Zhou, Honggang Chen, Weiwei Wang, Yicheng Wang, Juanjuan Chen, Xueqian Yang and Xuan Zhang
Water 2025, 17(15), 2352; https://doi.org/10.3390/w17152352 (registering DOI) - 7 Aug 2025
Abstract
The efficient and rational development of hydropower in the Lancang–Mekong River Basin can promote green energy transition, reduce carbon emissions, prevent and mitigate flood and drought disasters, and ensure the sustainable development of the entire basin. In this study, based on publicly available [...] Read more.
The efficient and rational development of hydropower in the Lancang–Mekong River Basin can promote green energy transition, reduce carbon emissions, prevent and mitigate flood and drought disasters, and ensure the sustainable development of the entire basin. In this study, based on publicly available hydrometeorological observation data and satellite remote sensing monitoring data from 2001 to 2020, a machine learning model of the Lancang–Mekong Basin was developed to reconstruct the basin’s hydrological processes, and identify the occurrence patterns and influencing mechanisms of water-related hazards. The results show that, against the background of climate change, the Lancang–Mekong Basin is affected by the increasing frequency and intensity of extreme precipitation events. In particular, Rx1day, Rx5day, R10mm, and R95p (extreme precipitation indicators determined by the World Meteorological Organization’s Expert Group on Climate Change Monitoring and Extreme Climate Events) in the northwestern part of the Mekong River Basin show upward trends, with the average maximum daily rainfall increasing by 1.8 mm/year and the total extreme precipitation increasing by 18 mm/year on average. The risks of flood and drought disasters will continue to rise. The flood peak period is mainly concentrated in August and September, with the annual maximum flood peak ranging from 5600 to 8500 m3/s. The Stung Treng Station exhibits longer drought duration, greater severity, and higher peak intensity than the Chiang Saen and Pakse Stations. At the Pakse Station, climate change and hydropower development have altered the non-drought proportion by −12.50% and +15.90%, respectively. For the Chiang Saen Station, the fragmentation degree of the drought index time series under the baseline, naturalized, and hydropower development scenarios is 0.901, 1.16, and 0.775, respectively. These results indicate that hydropower development has effectively reduced the frequency of rapid drought–flood transitions within the basin, thereby alleviating pressure on drought management efforts. The regulatory role of the cascade reservoirs in the Lancang River can mitigate risks posed by climate change, weaken adverse effects, reduce flood peak flows, alleviate hydrological droughts in the dry season, and decrease flash drought–flood transitions in the basin. The research findings can enable basin managers to proactively address climate change, develop science-based technical pathways for hydropower dispatch, and formulate adaptive disaster prevention and mitigation strategies. Full article
(This article belongs to the Section Water and Climate Change)
15 pages, 3574 KiB  
Article
Optimizing Sunflower Husk Pellet Combustion for B2B Bioenergy Commercialization
by Penka Zlateva, Nevena Mileva, Mariana Murzova, Kalin Krumov and Angel Terziev
Energies 2025, 18(15), 4189; https://doi.org/10.3390/en18154189 - 7 Aug 2025
Abstract
This study analyses the potential of using sunflower husks as an energy source by producing bio-pellets and evaluating their combustion process in residential settings. As one of the leading sunflower producers in the European Union, Bulgaria generates significant agricultural residues with high, yet [...] Read more.
This study analyses the potential of using sunflower husks as an energy source by producing bio-pellets and evaluating their combustion process in residential settings. As one of the leading sunflower producers in the European Union, Bulgaria generates significant agricultural residues with high, yet underutilized, energy potential. This study employs a combination of experimental data and numerical modelling aided by ANSYS 2024 R1 to analyse the combustion of sunflower husk pellets in a hot water boiler. The importance of balanced air distribution for achieving optimal combustion, reduced emissions, and enhanced thermal efficiency is emphasized by the results of a comparison of two air supply regimes. It was found that a secondary air-dominated air supply regime results in a more uniform temperature field and a higher degree of oxidation of combustible components. These findings not only confirm the technical feasibility of sunflower husk pellets but also highlight their commercial potential as a sustainable, low-cost energy solution for agricultural enterprises and rural heating providers. The research indicates that there are business-to-business (B2B) market opportunities for biomass producers, boiler manufacturers, and energy distributors who wish to align themselves with EU green energy policies and the growing demand for solutions that support the circular economy. Full article
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16 pages, 2179 KiB  
Article
The Coupling Mechanism of the Electricity–Gas System and Assessment of Attack Resistance Based on Interdependent Networks
by Qingyu Zou and Lin Yan
Eng 2025, 6(8), 193; https://doi.org/10.3390/eng6080193 - 6 Aug 2025
Abstract
Natural gas plays a critical role in integrated energy systems. In this context, the present study proposes an optimization model for the electricity–gas coupling system, grounded in the theory of interdependent networks. By integrating network topology parameters with real-time operational metrics, the model [...] Read more.
Natural gas plays a critical role in integrated energy systems. In this context, the present study proposes an optimization model for the electricity–gas coupling system, grounded in the theory of interdependent networks. By integrating network topology parameters with real-time operational metrics, the model substantially enhances system robustness and adaptability. To quantify nodal vulnerability and importance, the study introduces two novel evaluation indicators: the Electric Potential–Closeness Fusion Indicator (EPFI) for power networks and the Pressure Difference–Closeness Comprehensive Indicator (PDCI) for natural gas systems. Leveraging these indicators, three coupling paradigms—assortative, disassortative, and random—are systematically constructed and analyzed. System resilience is assessed through simulation experiments incorporating three attack strategies: degree-based, betweenness centrality-based, and random node removal. Evaluation metrics include network efficiency and the variation in the size of the largest connected subgraph under different coupling configurations. The proposed framework is validated using a hybrid case study that combines the IEEE 118-node electricity network with a 20-node Belgian natural gas system, operating under a unidirectional gas-to-electricity energy flow model. Results confirm that the disassortative coupling configuration, based on EPFI and PDCI indicators, exhibits superior resistance to network perturbations, thereby affirming the effectiveness of the model in improving the robustness of integrated energy systems. Full article
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25 pages, 3220 KiB  
Article
Distributed Energy Management for Ship-Integrated Energy System Under Marine Environmental Risk Field
by Yuxin Zhang, Yang Xiao and Tieshan Li
Energies 2025, 18(15), 4163; https://doi.org/10.3390/en18154163 - 6 Aug 2025
Abstract
To reduce carbon emissions in the shipping industry, the energy management problem of the ship-integrated energy system (S-IES) is analyzed in this paper. Firstly, a marine environmental risk field model is constructed to quantify the degree of hazard when designing the sailing route. [...] Read more.
To reduce carbon emissions in the shipping industry, the energy management problem of the ship-integrated energy system (S-IES) is analyzed in this paper. Firstly, a marine environmental risk field model is constructed to quantify the degree of hazard when designing the sailing route. Meanwhile, an energy management model that considers both economic and environmental benefits is developed to enhance the penetration rate of renewable resources. Subsequently, a distributed energy management algorithm based on finite-time consensus theory is proposed to ensure a rapid and accurate response to load demand. Moreover, a mathematical analysis is provided to demonstrate the algorithm’s effectiveness. Finally, the sea area between Singapore Port (Singapore) and Penang Port (Malaysia) is chosen as the simulation environment. The experimental results demonstrate the effectiveness of energy management for the S-IES. Full article
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22 pages, 3858 KiB  
Article
Thermodynamic Performance and Parametric Analysis of an Ice Slurry-Based Cold Energy Storage System
by Bingxin Zhao, Jie Li, Chenchong Zhou, Zicheng Huang and Nan Xie
Energies 2025, 18(15), 4158; https://doi.org/10.3390/en18154158 - 5 Aug 2025
Abstract
Subcooling-based ice slurry production faces challenges in terms of energy efficiency and operational stability, which limit its applications for large-scale cold energy storage. A thermodynamic model is established to investigate the effects of key control parameters, including evaporation temperature, condensation temperature, subcooling degree, [...] Read more.
Subcooling-based ice slurry production faces challenges in terms of energy efficiency and operational stability, which limit its applications for large-scale cold energy storage. A thermodynamic model is established to investigate the effects of key control parameters, including evaporation temperature, condensation temperature, subcooling degree, water flow rate, type of refrigerant, and adiabatic compression efficiency. The results show that using the refrigerant R161 achieves the highest energy efficiency, indicating that R161 is the optimal refrigerant in this research. When the evaporation and condensation temperatures are −10 °C and 30 °C, respectively, the system achieves the maximum comprehensive performance coefficient of 2.43. Moreover, under a flow velocity of 0.8 m/s and a temperature of 0.5 °C, the system achieves a peak ice production rate of 45.28 kg/h. A high water temperature and high flow velocity would significantly degrade the system’s ice production capacity. This research provides useful guidance for the design, optimization, and application of ice slurry-based cold energy storage systems. Full article
(This article belongs to the Section D: Energy Storage and Application)
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32 pages, 1960 KiB  
Article
Parallel Export and Differentiated Production in the Supply Chain of New Energy Vehicles
by Lingzhi Shao, Ziqing Zhu, Haiqun Li and Xiaoxue Ding
Systems 2025, 13(8), 662; https://doi.org/10.3390/systems13080662 - 5 Aug 2025
Abstract
Considering the supply chain of new energy vehicles composed of a local manufacturer, an authorized distributor in the domestic market, and a competitive manufacturer in the export market, this paper studies three different cases of parallel export as well as their decisions about [...] Read more.
Considering the supply chain of new energy vehicles composed of a local manufacturer, an authorized distributor in the domestic market, and a competitive manufacturer in the export market, this paper studies three different cases of parallel export as well as their decisions about prices, sales scale, and the degree of production differentiation. Three game models are constructed and solved under the cases of no parallel exports (CN), authorized distributors’ parallel exports (CR), and third-party parallel exports (CT), respectively, and the equilibrium analysis is carried out, and finally, the influence of relevant parameters is explored through numerical simulation. It is found that (1) the manufacturer’s decisions on production and sales are influenced by the characteristics of consumer preferences in local and export markets, the cost of differentiated production, and the consumer recognition of parallel exports; (2) the manufacturers’ profits will always be damaged by parallel exports; (3) differentiated production can reduce the negative impact of parallel exports under certain conditions, and then improve the profits of manufacturers; (4) manufacturers can increase their profits by improving the purchase intention of consumers in the local market, improve the level of production differentiation in the export market, or reducing the cost of differentiation. Full article
(This article belongs to the Section Supply Chain Management)
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21 pages, 14898 KiB  
Article
SSI Effects on Constant-Ductility Inelastic Displacement Ratio and Residual Displacement of Self-Centering Systems Under Pulse-Type Ground Motions
by Muberra Eser Aydemir
Appl. Sci. 2025, 15(15), 8661; https://doi.org/10.3390/app15158661 - 5 Aug 2025
Abstract
This study aims to examine the seismic response of self-centering single-degree-of-freedom (SDOF) systems exhibiting flag-shaped hysteretic behavior, while considering soil–structure interaction, in contrast to prior research that predominantly addressed conventional hysteretic behavior and overlooked soil flexibility. The inelastic displacement ratio, residual displacement, and [...] Read more.
This study aims to examine the seismic response of self-centering single-degree-of-freedom (SDOF) systems exhibiting flag-shaped hysteretic behavior, while considering soil–structure interaction, in contrast to prior research that predominantly addressed conventional hysteretic behavior and overlooked soil flexibility. The inelastic displacement ratio, residual displacement, and residual displacement ratio are used to analyze the seismic response of interacting structures. These structural response parameters are calculated based on the nonlinear dynamic analyses of SDOF systems subjected to 56 near-fault pulse-type ground motions. Analyses are conducted for varying values of ductility, energy dissipation coefficient, strain hardening ratio, aspect ratio, structural period, and normalized vibration period by pulse period of the record. New formulas to estimate the inelastic displacement ratio and residual displacement of self-centering SDOF systems with soil–structure interaction are developed based on a statistical analysis of the findings. Full article
(This article belongs to the Section Civil Engineering)
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20 pages, 18635 KiB  
Article
The Passive Optimization Design of Large- and Medium-Sized Gymnasiums in Hot Summer and Cold Winter Regions Oriented on Energy Saving: A Case Study of Shanghai
by Yuda Lyu, Ziyi Long, Ruifeng Zhou and Xu Gao
Buildings 2025, 15(15), 2745; https://doi.org/10.3390/buildings15152745 - 4 Aug 2025
Viewed by 140
Abstract
With the promotion of national fitness, the requirements for regulating indoor environments during non-competition periods are low and relatively flexible under the trend of composite sports buildings. To maximize the use of natural ventilation and lighting for energy savings, passive optimization design based [...] Read more.
With the promotion of national fitness, the requirements for regulating indoor environments during non-competition periods are low and relatively flexible under the trend of composite sports buildings. To maximize the use of natural ventilation and lighting for energy savings, passive optimization design based on building ontology has emerged as an effective strategy. This paper focuses on the spatial prototype of large- and medium-sized gymnasiums, optimizing key geometric design parameters and envelope structure parameters that influence energy consumption. This optimization employs a combination of orthogonal experiments and performance simulations. This study identifies the degree to which each factor affects energy consumption in the competition hall and determines the optimal low-energy consumption gymnasium prototype. The results reveal that the skylight area ratio is the most significant factor impacting the energy consumption of large- and medium-sized gymnasiums. The optimized gymnasium prototype reduced energy consumption by 5.3%~50.9% compared to all experimental combinations. This study provides valuable references and insights for architects during the initial stages of designing sports buildings to achieve low energy consumption. Full article
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25 pages, 13557 KiB  
Article
Mechanical Properties and Energy Absorption Characteristics of a Combined Gradient BCC Lattice Structure: A Numerical Study
by Xiangheng Zhao, Xiaoqiang Wang and Yunmiao Shang
Materials 2025, 18(15), 3652; https://doi.org/10.3390/ma18153652 - 4 Aug 2025
Viewed by 196
Abstract
As a new functional graded lattice structure construction strategy, the relative density gradient strategy has a promising future due to its ease of realization in various lattice structures. This paper proposes a BCC lattice structure combining two different lattice single cells. Based on [...] Read more.
As a new functional graded lattice structure construction strategy, the relative density gradient strategy has a promising future due to its ease of realization in various lattice structures. This paper proposes a BCC lattice structure combining two different lattice single cells. Based on this, the single cells of different structures are assigned different relative density gradients, resulting in 18 combined gradient lattice structures. Based on proving the experimental feasibility of numerical simulation, the mechanical properties and energy absorption characteristics of the combined gradient lattice structure are investigated by numerical simulation. When applied to composite lattice structures, the proposed wave-like gradient design significantly improves mechanical properties. Among the various gradient strategies examined, several have achieved mechanical performance close to that of uniform lattice structures. To some extent, this approach mitigates the common drawback of gradient lattice structures—where the relative density of the weakest layer is consistently lower than the interlayer relative density of uniform lattice structures—resulting in varying degrees of mechanical performance degradation compared to their uniform counterparts. The proposed linearly enhanced gradient strategy (Strategy-LE) possesses higher SEA and CLE values when the lattice structure is subjected to compressive loading, with an improvement of 6.36% in SEA and 61.6% in CLE over the uniform structure. Through the relative density gradient design, the adaptability of the BCC lattice structure in actual complex application scenarios is greatly enhanced, and the energy-absorbing properties of the lattice structure are greatly improved. Full article
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17 pages, 5214 KiB  
Article
Geothermal–Peltier Hybrid System for Air Cooling and Water Recovery
by Michele Spagnolo, Paolo Maria Congedo, Alessandro Buscemi, Gianluca Falcicchia Ferrara, Marina Bonomolo and Cristina Baglivo
Energies 2025, 18(15), 4115; https://doi.org/10.3390/en18154115 - 3 Aug 2025
Viewed by 177
Abstract
This study proposes a new air treatment system that integrates dehumidification, cooling, and water recovery using a Horizontal Air–Ground Heat Exchanger (HAGHE) combined with Peltier cells. The airflow generated by a fan flows through an HAGHE until it meets a septum on which [...] Read more.
This study proposes a new air treatment system that integrates dehumidification, cooling, and water recovery using a Horizontal Air–Ground Heat Exchanger (HAGHE) combined with Peltier cells. The airflow generated by a fan flows through an HAGHE until it meets a septum on which Peltier cells are placed, and then separates into two distinct streams that lap the two surfaces of the Peltier cells: one stream passes through the cold surfaces, undergoing both sensible and latent cooling with dehumidification; the other stream passes through the hot surfaces, increasing its temperature. The two treated air streams may then pass through a mixing chamber, where they are combined in the appropriate proportions to achieve the desired air supply conditions and ensure thermal comfort in the indoor environment. A Computational Fluid Dynamics (CFD) analysis was carried out to simulate the thermal interaction between the HAGHE and the surrounding soil. The simulation focused on a system installed under the subtropical climate conditions of Nairobi, Africa. The simulation results demonstrate that the HAGHE system is capable of reducing the air temperature by several degrees under typical summer conditions, with enhanced performance observed when the soil is moist. Condensation phenomena were triggered when the relative humidity of the inlet air exceeded 60%, contributing additional cooling through latent heat extraction. The proposed HAGHE–Peltier system can be easily powered by renewable energy sources and configured for stand-alone operation, making it particularly suitable for off-grid applications. Full article
(This article belongs to the Section A: Sustainable Energy)
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17 pages, 1546 KiB  
Article
Design and Optimization of Valve Lift Curves for Piston-Type Expander at Different Rotational Speeds
by Yongtao Sun, Qihui Yu, Zhenjie Han, Ripeng Qin and Xueqing Hao
Fluids 2025, 10(8), 204; https://doi.org/10.3390/fluids10080204 - 1 Aug 2025
Viewed by 122
Abstract
The piston-type expander (PTE), as the primary output component, significantly influences the performance of an energy storage system. This paper proposes a non-cam variable valve actuation system for the PTE, supported by a mathematical model. An enhanced S-curve trajectory planning method is used [...] Read more.
The piston-type expander (PTE), as the primary output component, significantly influences the performance of an energy storage system. This paper proposes a non-cam variable valve actuation system for the PTE, supported by a mathematical model. An enhanced S-curve trajectory planning method is used to design the valve lift curve. The study investigates the effects of various valve lift design parameters on output power and efficiency at different rotational speeds, employing orthogonal design and SPSS Statistics 27 (Statistical Product and Service Solutions) simulations. A grey comprehensive evaluation method is used to identify optimal valve lift parameters for each speed. The results show that valve lift parameters influence PTE performance to varying degrees, with intake duration having the greatest effect, followed by maximum valve lift, while intake end time has the least impact. The non-cam PTE outperforms the cam-based PTE. At 800 rpm, the optimal design yields 7.12 kW and 53.5% efficiency; at 900 rpm, 8.17 kW and 50.6%; at 1000 rpm, 9.2 kW and 46.8%; and at 1100 rpm, 12.09 kW and 41.2%. At these speeds, output power increases by 18.37%, 11.42%, 11.62%, and 9.82%, while energy efficiency improves by 15.01%, 15.05%, 14.24%, and 13.86%, respectively. Full article
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22 pages, 1929 KiB  
Article
Investigating Provincial Coupling Coordination Between Digital Infrastructure and Green Development in China
by Beibei Zhang, Zhenni Zhou, Juan Zheng, Zezhou Wu and Yan Liu
Buildings 2025, 15(15), 2724; https://doi.org/10.3390/buildings15152724 - 1 Aug 2025
Viewed by 213
Abstract
Digital technologies could facilitate green development by enhancing energy efficiency. However, existing research on coupling coordination between digital infrastructure and green development remains scarce. To fill this research gap, this study analyzes the spatio-temporal variations and barriers of coupling coordination. An evaluation index [...] Read more.
Digital technologies could facilitate green development by enhancing energy efficiency. However, existing research on coupling coordination between digital infrastructure and green development remains scarce. To fill this research gap, this study analyzes the spatio-temporal variations and barriers of coupling coordination. An evaluation index system is established and then the coupling relationship and the barrier factors between digital infrastructure and green development are analyzed. A provincial analysis is conducted by using data from China. The results in the study indicate (1) coupling coordination between digital infrastructure and green development exhibits a relatively low state, characterized by an overall upward trend; (2) noteworthy disparities are observed in the spatio-temporal pattern of the coupling coordination degree, reflecting the overall evolutionary trend from low to high coupling coordination, along with the characteristics of positive spatial correlation and high spatial concentration; and (3) obstacle factors are analyzed from the aspects of digital infrastructure and green development, emphasizing the construction of mobile phone base stations and investment in pollution control, among other aspects. This study contributes valuable insights for improvement paths for digital infrastructure and green development, offering recommendations for optimizing strategies to promote their coupled development. Full article
(This article belongs to the Special Issue Promoting Green, Sustainable, and Resilient Urban Construction)
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19 pages, 2806 KiB  
Article
Operating Solutions to Improve the Direct Reduction of Iron Ore by Hydrogen in a Shaft Furnace
by Antoine Marsigny, Olivier Mirgaux and Fabrice Patisson
Metals 2025, 15(8), 862; https://doi.org/10.3390/met15080862 - 1 Aug 2025
Viewed by 275
Abstract
The production of iron and steel plays a significant role in the anthropogenic carbon footprint, accounting for 7% of global GHG emissions. In the context of CO2 mitigation, the steelmaking industry is looking to potentially replace traditional carbon-based ironmaking processes with hydrogen-based [...] Read more.
The production of iron and steel plays a significant role in the anthropogenic carbon footprint, accounting for 7% of global GHG emissions. In the context of CO2 mitigation, the steelmaking industry is looking to potentially replace traditional carbon-based ironmaking processes with hydrogen-based direct reduction of iron ore in shaft furnaces. Before industrialization, detailed modeling and parametric studies were needed to determine the proper operating parameters of this promising technology. The modeling approach selected here was to complement REDUCTOR, a detailed finite-volume model of the shaft furnace, which can simulate the gas and solid flows, heat transfers and reaction kinetics throughout the reactor, with an extension that describes the whole gas circuit of the direct reduction plant, including the top gas recycling set up and the fresh hydrogen production. Innovative strategies (such as the redirection of part of the bustle gas to a cooling inlet, the use of high nitrogen content in the gas, and the introduction of a hot solid burden) were investigated, and their effects on furnace operation (gas utilization degree and total energy consumption) were studied with a constant metallization target of 94%. It has also been demonstrated that complete metallization can be achieved at little expense. These strategies can improve the thermochemical state of the furnace and lead to different energy requirements. Full article
(This article belongs to the Special Issue Recent Developments and Research on Ironmaking and Steelmaking)
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35 pages, 10962 KiB  
Article
A Preliminary Assessment of Offshore Winds at the Potential Organized Development Areas of the Greek Seas Using CERRA Dataset
by Takvor Soukissian, Natalia-Elona Koutri, Flora Karathanasi, Kimon Kardakaris and Aristofanis Stefatos
J. Mar. Sci. Eng. 2025, 13(8), 1486; https://doi.org/10.3390/jmse13081486 - 31 Jul 2025
Viewed by 190
Abstract
Τhe Greek Seas are one of the most favorable locations for offshore wind energy development in the Mediterranean basin. In 2023, the Hellenic Hydrocarbons & Energy Resources Management Company SA published the draft National Offshore Wind Farm Development Programme (NDP-OWF), including the main [...] Read more.
Τhe Greek Seas are one of the most favorable locations for offshore wind energy development in the Mediterranean basin. In 2023, the Hellenic Hydrocarbons & Energy Resources Management Company SA published the draft National Offshore Wind Farm Development Programme (NDP-OWF), including the main pillars for the design, development, siting, installation, and exploitation of offshore wind farms, along with the Strategic Environmental Impact Assessment. The NDP-OWF is under assessment by the relevant authorities and is expected to be finally approved through a Joint Ministerial Decision. In this work, the preliminary offshore wind energy assessment of the Greek Seas is performed using the CERRA wind reanalysis data and in situ measurements from six offshore locations of the Greek Seas. The in situ measurements are used in order to assess the performance of the reanalysis datasets. The results reveal that CERRA is a reliable source for preliminary offshore wind energy assessment studies. Taking into consideration the potential offshore wind farm organized development areas (OWFODA) according to the NDP-OWF, the study of the local wind characteristics is performed. The local wind speed and wind power density are assessed, and the wind energy produced from each OWFODA is estimated based on three different capacity density settings. According to the balanced setting (capacity density of 5.0 MW/km2), the annual energy production will be 17.5 TWh, which is equivalent to 1509.1 ktoe. An analysis of the wind energy correlation, synergy, and complementarity between the OWFODA is also performed, and a high degree of wind energy synergy is identified, with a very low degree of complementarity. Full article
(This article belongs to the Section Marine Energy)
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25 pages, 3263 KiB  
Article
Repurposing Nirmatrelvir for Hepatocellular Carcinoma: Network Pharmacology and Molecular Dynamics Simulations Identify HDAC3 as a Key Molecular Target
by Muhammad Suleman, Hira Arbab, Hadi M. Yassine, Abrar Mohammad Sayaf, Usama Ilahi, Mohammed Alissa, Abdullah Alghamdi, Suad A. Alghamdi, Sergio Crovella and Abdullah A. Shaito
Pharmaceuticals 2025, 18(8), 1144; https://doi.org/10.3390/ph18081144 - 31 Jul 2025
Viewed by 286
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic [...] Read more.
Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article
(This article belongs to the Section Pharmacology)
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