Search Results (19)

Blast furnace (BF) ironmaking remains one of the most efficient countercurrent processes; however, achieving further CO₂ emission reductions through conventional methods is increasingly challenging. Currently, BF ironmaking emits approximately 2.33 tonnes of fossil-derived CO₂ per tonne of crude steel cast. Integrating briquettes composed of biochar and in-plant fines into the BF process offers a promising short- to medium-term strategy for lowering emissions. This approach enables efficient recycling of fine residues and the substitution of fossil reductants with bio-based alternatives, thereby improving productivity while reducing energy and carbon intensity. This study investigates the reduction behavior of (i) biochar mixed with pellet fines, (ii) various in-plant residues individually, and (iii) briquettes composed of biochar and in-plant fines. The reduction rate of biochar–pellet fine mixtures was found to depend on biochar type, with pyrolyzed pine sawdust exhibiting the highest reactivity, and pyrolyzed contorta wood chips the lowest. A correlation between reduction rate and the alkali index of each char was established, although other factors such as char origin and physical properties also influenced reactivity. The effect of biochar addition (0, 5, and 10 wt.%) on the reduction of steelmaking residues was also studied. In general, biochar enhanced the reduction degree and shifted the reaction onset to lower temperatures. The produced briquettes maintained high mechanical integrity during and after reduction, regardless of biochar origin. Thermogravimetric and XRD analyses revealed that mass loss initiates with the dehydroxylation of cement phases and release of volatiles, followed by carbonate decomposition and reduction of higher oxides above 500 °C. At temperatures ≥ 850 °C, the remaining iron oxides were further reduced to metallic iron. Full article

Adoxophyes orana (Lepidoptera: Tortricidae) is a significant polyphagous leafroller that damages trees and shrubs in Rosaceae and other families. However, the molecular mechanisms by which this pest recognizes sex pheromones and host plant volatiles remain largely unknown. Tissue expression profiles indicated that two general odorant-binding proteins (AoraGOBP1 and AoraGOBP2) were more abundant in the antennae and wings of both sexes, with AoraGOBP1 being rich in the female head and abdomen. Temporal expression profiles showed that AoraGOBP1 was expressed at the highest level in 5 day-nmated adults, while AoraGOBP2 exhibited high expression in 5 day-unmated, 7 day-unmated, and mated female adults. Fluorescence competitive binding assays of heterologous expressed AoraGOBPs demonstrated that AoraGOBP2 strongly bound to the primary sex pheromone Z9-14:Ac, and two minor sex pheromones Z9-14:OH and Z11-14:OH, whereas AoraGOBP1 only showed a high binding affinity to Z9-14:Ac. What is more, AoraGOBP1 exhibited a broader binding spectrum for host plant volatiles than AoraGOBP2. Molecular dockings, molecular dynamic simulations, and per-residue binding free decompositions indicated that the van der Waals interaction was the predominant contributor to the binding free energy. Electrostatic interactions between aldehydes, or alcohols and AoraGOBPs stabilized the conformational structures. Phe12 from AoraGOBP1, and Phe13 from AoraGOBP2 were identified as the most important residues that contributed to bind free energy. Our findings provide a comprehensive insight into the molecular mechanisms of olfactory recognition in A. orana, facilitating the development of chemical ecology-based approaches for the control. Full article

This study takes the daily temperature series of Taipei City as an example and proposes a data projection method based on Empirical Mode Decomposition (EMD), which effectively resolves the challenge of modeling non-stationary sequences. According to the daily mean temperature records from 1971 to 2023, Taipei has experienced an average warming rate of 0.02 °C per year. After applying EMD, the data were decomposed into 12 intrinsic mode functions (IMFs) and one residual trend. Among them, IMF5, with a period of 352 days (approximately one year), contributes 78% of the total energy, representing the dominant climatic cycle component. In this study, daily temperatures were categorized into five thermal levels: Cold (<12 °C), Cool (12–18 °C), Moderate (18–27 °C), Warm (27–32 °C), and Hot (>32 °C). In addition, using a 5-year moving process based on the annual EMD results, the IMFs and residuals were recombined to generate 390,625 synthetic sequences per year. Results show that the monthly mean temperatures of each year’s simulations closely match the observations, capturing the non-stationary characteristics of temperature variations. The overall classification accuracy of simulated versus observed daily temperature categories ranges from 60% to 71%, with an average of 65.1%. In summary, the EMD combined with the 5-year moving process developed in this study demonstrates a helpful data projection approach with effective reconstruction of periodic structures and stable simulation accuracy. It offers practical value for reconstructing urban climate variability, conducting risk assessments, and analyzing long-term warming trends. Moreover, it serves as a vital tool for modeling non-stationary climate data and supporting future projections. Full article

Background/Objectives: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin–BSA complex under physiological and slightly elevated temperatures. Methods: Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. Results: Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein’s intramolecular interaction network. Conclusions: These findings offer insights into the dynamic behavior of the noraucuparin–BSA complex and enhance the understanding of serum albumin–ligand interactions, with potential implications for drug delivery systems. Full article

Understanding the behavior of pressure increases in lithium-ion (Li-ion) cells is essential for prolonging the lifespan of Li-ion battery cells and minimizing the safety risks associated with cell aging. This work investigates the effects of C-rates and temperature on pressure behavior in commercial lithium cobalt oxide (LCO)/graphite pouch cells. The battery is volumetrically constrained, and the mechanical pressure response is measured using a force gauge as the battery is cycled. The effect of the C-rate (1C, 2C, and 3C) and ambient temperature (10 °C, 25 °C, and 40 °C) on the increase in battery pressure is investigated. By analyzing the change in the minimum, maximum, and pressure difference per cycle, we identify and discuss the effects of different factors (i.e., SEI layer damage, electrolyte decomposition, lithium plating) on the pressure behavior. Operating at high C-rates or low temperatures rapidly increases the residual pressure as the battery is cycled. The results suggest that lithium plating is predominantly responsible for battery expansion and pressure increase during the cycle aging of Li-ion cells rather than electrolyte decomposition. Electrochemical impedance spectroscopy (EIS) measurements can support our conclusions. Postmortem analysis of the aged cells was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) to confirm the occurrence of lithium plating and film growth on the anodes of the aged cells. This study demonstrates that pressure measurements can provide insights into the aging mechanisms of Li-ion batteries and can be used as a reliable predictor of battery degradation. Full article

The outbreak of coronavirus disease 2019 (COVID-19) has sparked an urgent demand for advanced diagnosis and vaccination worldwide. The discovery of high-affinity ligands is of great significance for vaccine and diagnostic reagent manufacturing. Targeting the receptor binding domain (RBD) from the spike protein of severe acute respiratory syndrome-coronavirus 2, an interface at the outer surface of helices on the Z domain from protein A was introduced to construct a virtual library for the screening of Z_RBD affibody ligands. Molecular docking was performed using HADDOCK software, and three potential Z_RBD affibodies, Z_RBD-02, Z_RBD-04, and Z_RBD-07, were obtained. Molecular dynamics (MD) simulation verified that the binding of Z_RBD affibodies to RBD was driven by electrostatic interactions. Per-residue free energy decomposition analysis further substantiated that four residues with negative-charge characteristics on helix α1 of the Z domain participated in this process. Binding affinity analysis by microscale thermophoresis showed that Z_RBD affibodies had high affinity for RBD binding, and the lowest dissociation constant was 36.3 nmol/L for Z_RBD-07 among the three potential Z_RBD affibodies. Herein, Z_RBD-02 and Z_RBD-07 affibodies were selected for chromatographic verifications after being coupled to thiol-activated Sepharose 6 Fast Flow (SepFF) gel. Chromatographic experiments showed that RBD could bind on both Z_RBD SepFF gels and was eluted by 0.1 mol/L NaOH. Moreover, the Z_RBD-07 SepFF gel had a higher affinity for RBD. This research provided a new idea for the design of affibody ligands and validated the potential of affibody ligands in the application of RBD purification from complex feedstock. Full article

Ecological footprint (EF) is used to measure the energy and resources that are consumed by human beings, and it is used to calculate the energy that ecological services can provide to determine the gap between human behavior and what the earth can tolerate so as to ensure that human activities and sustainable development fall within this range. Therefore, it is crucial to research the influencing factors of EF. In this study, the ensemble empirical mode decomposition (EEMD) method was used to decompose China’s per capita ecological footprint from 1961 to 2018 into four intrinsic mode functions (IMFs) and a residual (R) and to conduct factor detection and interaction detection on both each obtained sequence and the original sequence. In order to examine the contributing factors, 15 independent variables representing the economic, social, and environmental pillars of sustainable development were chosen. The outcome under the interaction factor is more logical than the result under the single factor. Under the interaction factor of climate, the short-term changes in the number of doctors per 1000 people, long-term population density, carbon dioxide emissions, and average life expectancy interact with each other and the trend in CO₂ emissions to affect the change in ecological footprint. Full article

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from −81.304 to −1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (−1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [−873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2. Full article

To explore the mechanistic origin that determines the binding affinity of SARS-CoV-2 spike receptor binding domain (RBD) to human angiotensin converting enzyme 2 (ACE2), we constructed the homology models of RBD-ACE2 complexes of four Omicron subvariants (BA.1, BA.2, BA.3 and BA.4/5), and compared them with wild type complex (RBD_WT-ACE2) in terms of various structural dynamic properties by molecular dynamics (MD) simulations and binding free energy (BFE) calculations. The results of MD simulations suggest that the RBDs of all the Omicron subvariants (RBD_OMIs) feature increased global structural fluctuations when compared with RBD_WT. Detailed comparison of BFE components reveals that the enhanced electrostatic attractive interactions are the main determinant of the higher ACE2-binding affinity of RBD_OMIs than RBD_WT, while the weakened electrostatic attractive interactions determine RBD of BA.4/5 subvariant (RBD_BA.4/5) lowest ACE2-binding affinity among all Omicron subvariants. The per-residue BFE decompositions and the hydrogen bond (HB) networks analyses indicate that the enhanced electrostatic attractive interactions are mainly through gain/loss of the positively/negatively charged residues, and the formation or destruction of the interfacial HBs and salt bridges can also largely affect the ACE2-binding affinity of RBD. It is worth pointing out that since Q493R plays the most important positive contribution in enhancing binding affinity, the absence of this mutation in RBD_BA.4/5 results in a significantly weaker binding affinity to ACE2 than other Omicron subvariants. Our results provide insight into the role of electrostatic interactions in determining of the binding affinity of SARS-CoV-2 RBD to human ACE2. Full article

The Nerve Growth Factor (NGF) belongs to the neurothrophins protein family involved in the survival of neurons in the nervous system. The interaction of NGF with its high-affinity receptor TrkA mediates different cellular pathways related to Alzheimer’s disease, pain, ocular dysfunction, and cancer. Therefore, targeting NGF-TrkA interaction represents a valuable strategy for the development of new therapeutic agents. In recent years, experimental studies have revealed that peptides belonging to the N-terminal domain of NGF are able to partly mimic the biological activity of the whole protein paving the way towards the development of small peptides that can selectively target specific signaling pathways. Hence, understanding the molecular basis of the interaction between the N-terminal segment of NGF and TrkA is fundamental for the rational design of new peptides mimicking the NGF N-terminal domain. In this study, molecular dynamics simulation, binding free energy calculations and per-residue energy decomposition analysis were combined in order to explore the molecular recognition pattern between the experimentally active NGF(1–14) peptide and TrkA. The results highlighted the importance of His4, Arg9 and Glu11 as crucial residues for the stabilization of NGF(1–14)-TrkA interaction, thus suggesting useful insights for the structure-based design of new therapeutic peptides able to modulate NGF-TrkA interaction. Full article

As a member of the death-associated protein kinase (DAPK) family, STK17B plays an important role in the regulation of cellular apoptosis and has been considered as a promising drug target for hepatocellular carcinoma. However, the highly conserved ATP-binding site of protein kinases represents a challenge to design selective inhibitors for a specific DAPK isoform. In this study, molecular docking, multiple large-scale molecular dynamics (MD) simulations, and binding free energy calculations were performed to decipher the molecular mechanism of the binding selectivity of PKIS43 toward STK17B against its high homology STK17A. MD simulations revealed that STK17A underwent a significant conformational arrangement of the activation loop compared to STK17B. The binding free energy predictions suggested that the driving force to control the binding selectivity of PKIS43 was derived from the difference in the protein–ligand electrostatic interactions. Furthermore, the per-residue free energy decomposition unveiled that the energy contribution from Arg41 at the phosphate-binding loop of STK17B was the determinant factor responsible for the binding specificity of PKIS43. This study may provide useful information for the rational design of novel and potent selective inhibitors toward STK17B. Full article

Under the oxidative stress condition, the small RNA (sRNA) OxyS that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in the defection of gene regulation. However, how the Hfq protein interacts with sRNA OxyS and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result was correlated with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly came from the increased van der Waals interactions (vdW). This research explored the binding mechanism between Oxys and chaperone protein Hfq and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights into the mechanism of gene expression regulation affected by protein mutations. Full article

Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < −15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA–βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9–2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0–100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149–151) compared to FA–FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems. Full article

Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking using the C-I-TASSER-predicted TMPRSS2 catalytic domain model suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time (100 ns) simulations. The molecular mechanics/generalized Born surface area-binding free energy assessment and per-residue energy decomposition analysis also supported the strong binding interactions between TMPRSS2 and the proposed drugs. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups. Full article

Recent studies have identified cyclic GMP-AMP synthase (cGAS) as an important target for treating autoimmune diseases, and several inhibitors of human cGAS (hcGAS) and their structures in complexation with hcGAS have been reported. However, the mechanisms via which these inhibitors interact with hcGAS are not completely understood. Here, we aimed to assess the performance of molecular mechanics/Poisson–Boltzmann solvent-accessible surface area (MM/PBSA) in evaluating the binding affinity of various hcGAS inhibitors and to elucidate their detailed interactions with hcGAS from an energetic viewpoint. Using molecular dynamics (MD) simulation and MM/PBSA approaches, the estimated free energies were in good agreement with the experimental ones, with a Pearson’s correlation coefficient and Spearman’s rank coefficient of 0.67 and 0.46, respectively. In per-residue energy decomposition analysis, four residues, K362, R376, Y436, and K439 in hcGAS were found to contribute significantly to the binding with inhibitors via hydrogen bonding, salt bridges, and various π interactions, such as π· · ·π stacking, cation· · ·π, hydroxyl· · ·π, and alkyl· · ·π interactions. In addition, we discussed other key interactions between specific residues and ligands, in particular, between H363 and JUJ, F379 and 9BY, and H437 and 8ZM. The sandwiched structures of the inhibitor bound to the guanidinium group of R376 and the phenyl ring of Y436 were also consistent with the experimental data. The results indicated that MM/PBSA in combination with other virtual screening methods, could be a reliable approach to discover new hcGAS inhibitors and thus is valuable for potential treatments of cGAS-dependent inflammatory diseases. Full article