Search Results (667)

The core perturbome is defined as a central response to multiple disturbances, functioning as a complex molecular network to overcome the disruption of homeostasis under stress conditions, thereby promoting tolerance and survival under stress conditions. Based on the biological and clinical relevance of Escherichia coli and Staphylococcus aureus, we characterized their molecular responses to multiple perturbations. Gene expression data from E. coli (8815 target genes—based on a pangenome—across 132 samples) and S. aureus (3312 target genes across 156 samples) were used. Accordingly, this study aimed to identify and describe the functionality of the core perturbome of these two prokaryotic models using a machine learning approach. For this purpose, feature selection and classification algorithms (KNN, RF and SVM) were implemented to identify a subset of genes as core molecular signatures, distinguishing control and perturbation conditions. After verifying effective dimensional reduction (with median accuracies of 82.6% and 85.1% for E. coli and S. aureus, respectively), a model of molecular interactions and functional enrichment analyses was performed to characterize the selected genes. The core perturbome was composed of 55 genes (including nine hubs) for E. coli and 46 (eight hubs) for S. aureus. Well-defined interactomes were predicted for each model, which are jointly associated with enriched pathways, including energy and macromolecule metabolism, DNA/RNA and protein synthesis and degradation, transcription regulation, virulence factors, and other signaling processes. Taken together, these results may support the identification of potential therapeutic targets and biomarkers of stress responses in future studies. Full article

In recent years, growing concerns over environmental degradation and deepening awareness of the necessity of sustainable development have propelled green and low-carbon energy transition into a focal issue for both academia and policymakers. By decomposing energy transition into the transformation of energy structure and the upgrading of energy efficiency, this study investigates the impact and mechanisms of green finance on energy transition across 30 provinces (municipalities and autonomous regions) in China, with the exception of Tibet. In addition, the impact of climate change is incorporated into the analytical framework. Empirical results demonstrate that green finance development significantly accelerates energy transition, a conclusion robust to rigorous validation. Analysis of the mechanism shows that green finance promotes energy transition through the facilitation of technological innovation and the upgrade of industrial structures. Moreover, empirical evidence reveals that climate change undermines the promotional influence of sustainable finance on energy system transformation. The magnitude of this suppression varies nonlinearly across provincial jurisdictions with differing energy transition progress. Regional heterogeneity analyses further uncover marked discrepancies in climate–finance interactions, demonstrating amplified effects in coastal economic hubs, underdeveloped western provinces, and regions with mature eco-financial markets. According to these findings, actionable policy suggestions are put forward to strengthen green finance and accelerate energy transition. Full article

This work presents a high-fidelity simulation of the Peach Bottom turbine trip (PBTT) benchmark using the Virtual Environment for Reactor Applications (VERA), a multiphysics reactor modeling tool developed by the U.S. Department of Energy’s Consortium for Advanced Simulation of Light Water Reactors energy innovation hub. The PBTT benchmark, based on a 1977 transient event at the end of cycle 2 in a General Electric Type-4 boiling water reactor (BWR), is a critical test case for validating core physics models with thermal feedback during rapid reactivity events. VERA was employed to perform end-to-end, pin-resolved simulations from conditions at the beginning of cycle 1 through the turbine-trip transient, incorporating detailed neutron transport, fuel depletion, and subchannel thermal hydraulics. The simulation reproduced key benchmark observables with high accuracy: the peak power excursion occurred at 0.75 s, matching the scram time and closely aligning with the benchmark average of 0.742 s; the simulated maximum power spike was approximately 7600 MW, which is within 3% of the benchmark average of 7400 MW; and void-collapse dynamics were consistent with benchmark expectations. Reactivity predictions during cycles 1 and 2 remained within 1500 pcm and 400 pcm of criticality, respectively. These results confirm VERA’s ability to model complex coupled neutronic and thermal hydraulic behavior in a BWR turbine-trip transient, which will support its use in future studies of modeling dryout, fuel performance, and uncertainty quantification for transients of this type. Full article

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

Achieving carbon emission reductions in the residential building sector while maintaining economic growth represents a global challenge, particularly in rapidly developing regions with internal disparities. This study examines Jiangsu Province in eastern China—a economic hub with north-south development gradients—to develop an integrated framework for differentiated carbon reduction pathways. The methodology combines spatial autocorrelation analysis, logarithmic mean Divisia index (LMDI) decomposition, system dynamics modeling, and Tapio decoupling analysis to examine urban residential building emissions across three regions from 2016–2022. Results reveal significant spatial clustering of emissions (Moran’s I peaking at 0.735), with energy consumption per unit area as the dominant driver across all regions (contributing 147.61%, 131.82%, and 147.57% respectively). Scenario analysis demonstrates that energy efficiency policies can reduce emissions by 10.1% while maintaining 99.2% of economic performance, enabling carbon peak achievement by 2030. However, less developed northern regions emerge as binding constraints, requiring technology investments. Decoupling analysis identifies region-specific optimal pathways: conventional development for advanced regions, balanced approaches for transitional areas, and subsidies for lagging regions. These findings challenge assumptions about environment-economy trade-offs and provide a replicable framework for designing differentiated climate policies in heterogeneous territories, offering insights for similar regions worldwide navigating the transition to sustainable development. Full article

Our regression analysis documents that energy policies to promote renewable energy development, as well as hydroelectric imports from Canada, lead to short-run reductions in average electricity prices (also known as merit-order effects) throughout the Northeast United States. Changes in the reliance upon renewable energy in one of the Northeast’s three interconnected electricity markets will impact wholesale prices in the other two. The retirement of a 1000 MW nuclear plant can increase prices by about 9% in the Independent System Operator of New England market and 7% in the New York Independent System Operator market in the short run at reference hubs, while also raising prices in neighboring markets. Some proposed large-scale off-shore wind farms would not only lower prices in local markets at the reference hubs modeled but would also lower prices in neighboring markets. Full article

Adenosine receptors (ARs) are G protein-coupled receptors that are widely expressed across tissues, traditionally associated with cardiovascular, neurological, and immune regulation. Recent studies, however, have highlighted their non-canonical functions, revealing critical roles in metabolism, immunometabolism, and epigenetic regulation. AR subtypes, particularly A2A and A2B, modulate glucose and lipid metabolism, mitochondrial activity, and energy homeostasis. In immune cells, AR signaling influences metabolic reprogramming and polarization through key regulators such as mTOR, AMPK, and HIF-1α, contributing to immune tolerance or activation depending on the context. Additionally, ARs have been implicated in epigenetic modulation, affecting DNA methylation, histone acetylation, and non-coding RNA expression via metabolite-sensitive mechanisms. Therapeutically, AR-targeting agents are being explored for cancer and chronic inflammatory diseases. While clinical trials with A2A antagonists in oncology show encouraging results, challenges remain due to receptor redundancy, systemic effects, and the need for tissue-specific selectivity. Future strategies involve biased agonism, allosteric modulators, and combination therapies guided by biomarker-based patient stratification. Overall, ARs are emerging as integrative hubs connecting extracellular signals with cellular metabolic and epigenetic machinery. Understanding these non-canonical roles may unlock novel therapeutic opportunities across diverse disease landscapes. Full article

This work studies and analyzes the transition from a linear to a circular economy through wastewater treatment and resource recovery. As wastewater volumes grow, sustainable management becomes critical. This study highlights the reuse of treated effluent, beneficial sludge utilization, and energy generation via anaerobic digestion. Wastewater treatment plants should be envisioned as hubs for recovering water, materials, and energy, rather than disposal facilities. Emphasizing resource efficiency, the circular economy approach offers viable solutions to challenges related to resource scarcity, climate change, and ecological impact. Full article

In 2022, the Russia–Ukraine conflict has severely impacted the EU’s energy supply chain, and the EU’s natural gas import pattern has begun to reconstruct, and exploring the spatiotemporal differentiation of EU natural gas trade and its driving factors is the basis for improving the resilience of its supply chain and ensuring the stable supply of energy resources. This paper summarizes the law of the change of its import volume by using the complex network method, constructs a multi-dimensional index system such as demand, economy, and security, and uses the geographic detector model to mine the driving factors affecting the spatiotemporal evolution of natural gas imports in EU countries and propose different sustainable development paths. The results show that from 2000 to 2023, Europe’s natural gas imports generally show an upward trend, and the import structure has undergone great changes, from pipeline gas dominance to LNG diversification. After the conflict between Russia and Ukraine, the number of import source countries has increased, the market network has become looser, France has become the core hub of the EU natural gas market, the importance of Russia has declined rapidly, and the status of countries in the United States, North Africa, and the Middle East has increased rapidly; natural gas consumption is the leading factor in the spatiotemporal differentiation of EU natural gas imports, and the influence of import distance and geopolitical risk is gradually expanding, and the proportion of energy consumption is significantly higher than that of other factors in the interaction with other factors. Combined with the driving factors, three different evolutionary directions of natural gas imports in EU countries are identified, and energy security paths such as improving supply chain control capabilities, ensuring export stability, and using location advantages to become hub nodes are proposed for different development trends. Full article

Hydrogen is being increasingly integrated into the international trade system as a clean and flexible energy carrier, motivated by the global energy transition and carbon neutrality objectives. The rapid expansion of the global hydrogen trade network has simultaneously exposed several sustainability challenges, including a centralized structure, overdependence on key countries, and limited resilience to external disruptions. Based on this, we develop a risk propagation model that incorporates the absorption capacity of nodes to simulate the propagation of supply shortage risks within the global hydrogen trade network. Furthermore, we propose a composite sustainability index constructed from structural, economic, and environmental resilience indicators, enabling a systematic assessment of the network’s sustainable development capacity under external shock scenarios. Findings indicate the following: (1) The global hydrogen trade network is undergoing a structural shift from a Western Europe-dominated unipolar configuration to a more polycentric pattern. Countries such as China and Singapore are emerging as key hubs linking Eurasian regions, with trade relationships among nations becoming increasingly dense and diversified. (2) Although supply shortage shocks trigger structural disturbances, economic losses, and risks of carbon rebound, their impacts are largely concentrated in a limited number of hub countries, with relatively limited disruption to the overall sustainability of the system. (3) Countries exhibit significant heterogeneity in structural, economic, and environmental resilience. Risk propagation demonstrates an uneven pattern characterized by hub-induced disruptions, chain-like transmission, and localized clustering. Accordingly, policy recommendations are proposed, including the establishment of a polycentric coordination mechanism, the enhancement of regional emergency coordination mechanisms, and the advancement of differentiated capacity-building efforts. Full article

Energy storage plays an essential role in stabilizing fluctuations in renewable energy sources such as wind and solar, enabling surplus electricity retention, and delivering dynamic frequency regulation. However, relying solely on a single form of storage often proves insufficient due to constraints in performance, capacity, and cost-effectiveness. To tackle frequency regulation challenges in remote desert-based renewable energy hubs—where traditional power infrastructure is unavailable—this study introduces a planning framework for an electro-hydrogen energy storage system with grid-forming capabilities, designed to supply both inertia and frequency response. At the system design stage, a direct current (DC) transmission network is modeled, integrating battery and hydrogen storage technologies. Using this configuration, the capacity settings for both grid-forming batteries and hydrogen units are optimized. This study then explores how hydrogen systems—comprising electrolyzers, storage tanks, and fuel cells—and grid-forming batteries contribute to inertial support. Virtual inertia models are established for each technology, enabling precise estimation of the total synthetic inertia provided. At the operational level, this study addresses stability concerns stemming from renewable generation variability by introducing three security indices. A joint optimization is performed for virtual inertia constants, which define the virtual inertia provided by energy storage systems to assist in frequency regulation, and primary frequency response parameters within the proposed storage scheme are optimized in this model. This enhances the frequency modulation potential of both systems and confirms the robustness of the proposed approach. Lastly, a real-world case study involving a 13 GW renewable energy base in Northwest China, connected via a ±10 GW HVDC export corridor, demonstrates the practical effectiveness of the optimization strategy and system configuration. Full article

As global climate change intensifies and the transition to clean energy accelerates, lithium-ion batteries—critical components of electric vehicles—are becoming increasingly vital in international trade networks. This study investigates the structural evolution and determinants of the electric vehicle lithium-ion battery trade network among European Union (EU) member states from 2012 to 2023, employing social network analysis and the multiple regression quadratic assignment procedure method. The findings demonstrate the transformation of the network from a centralized and loosely connected structure, with Germany as the dominant hub, to a more interconnected and decentralized system in which Poland and Hungary emerge as the leading players. Key network metrics, such as the density, clustering coefficients, and average path lengths, reveal increased regional trade connectivity and enhanced supply chain efficiency. The analysis identifies geographic and economic proximity, logistics performance, labor cost differentials, energy resource availability, and venture capital investment as significant drivers of trade flows, highlighting the interaction among spatial, economic, and infrastructural factors in shaping the network. Based on these findings, this study underscores the need for targeted policy measures to support Central and Eastern European countries, including investment in logistics infrastructure, technological innovation, and regional cooperation initiatives, to strengthen their integration into the supply chain and bolster their export capacity. Furthermore, fostering balanced inter-regional collaborations is essential in building a resilient trade network. Continued investment in transportation infrastructure and innovation is recommended to sustain the EU’s competitive advantage in the global electric vehicle lithium-ion battery supply chain. Full article

Forensic entomotoxicology is a subdiscipline that utilizes necrophagous insects as bioindicators for detecting drugs and toxicants in decomposed remains, particularly in cases where conventional biological matrices are no longer available. Toxic substances can profoundly alter insect development, physiology, and community succession, potentially impacting the accuracy of postmortem interval (PMI) estimation. This review systematically summarizes the effects of various xenobiotics, including pesticides, illicit drugs, sedatives, heavy metals, and antibiotics on larval growth, physiological traits, and gut microbial composition in forensically relevant flies. However, most studies to date have relied primarily on phenotypic observations, with limited insight into underlying molecular mechanisms. Significant interspecies and dose-dependent variability also exists in the absorption, metabolism, and physiological responses to xenobiotics. We highlight recent advances in multi-omics technologies that facilitate the identification of molecular biomarkers associated with xenobiotic exposure, particularly within the insect detoxification system. Key components such as cytochrome P450 monooxygenases (P450s), glutathione S-transferases (GSTs), and ATP-binding cassette (ABC) transporters play essential roles in xenobiotic metabolism and insecticide resistance. Additionally, the insect fat body serves as a central hub for detoxification, hormonal regulation, and energy metabolism. It integrates signals related to xenobiotic exposure and modulates larval development, making it a promising model for future mechanistic studies in insect toxicology. Altogether, this review offers a comprehensive and reliable framework for understanding the complex interactions between toxic substance exposure, insect ecology, and decomposition in forensic investigations. Full article

This research evaluates the mechanical properties, environmental impacts, and cost-effectiveness of Hub Coal fly ash (FA)-based geopolymer concrete (FAGPC) as a sustainable alternative to ordinary Portland cement (OPC) concrete. This local FA has not been investigated previously. A total of 24 FAGPC mixes were tested under both ambient and heat curing conditions, varying the molarities of sodium hydroxide (NaOH) solution (10-M, 12-M 14-M and 16-M), sodium silicate to sodium hydroxide (Na₂SiO₃/NaOH) ratios (1.5, 2.0, and 2.5), and alkaline activator solution to fly ash (AAS/FA) ratios (0.5 and 0.6). The test results demonstrated that increasing NaOH molarity enhances the compressive strength (CS.) by 145% under ambient curing, with a peak CS. of 32.8 MPa at 16-M NaOH, and similarly, flexural strength (FS.) increases by 90% with a maximum FS. of 6.5 MPa at 14-M NaOH. Conversely, increasing the Na₂SiO₃/NaOH ratio to 2.5 reduced the CS. and FS. of ambient-cured specimens by 12.5% and 10.5%, respectively. Microstructural analysis revealed that higher NaOH molarity produced a denser, more homogeneous matrix, supported by increased Si–O–Al bond formation observed through energy-dispersive X-ray spectrometry. Environmentally, FAGPC demonstrated a 35–40% reduction in embodied CO₂ emissions compared to OPC, although the production costs of FAGPC were 30–35% higher, largely due to the expense of alkaline activators. These findings highlight the potential of FAGPC as a low-carbon alternative to OPC concrete, balancing enhanced mechanical performance with sustainability. New, green, and cheap activation solutions are sought for a new generation of more sustainable and affordable FAGPC. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article