Search Results (77)

Aromatic compounds are abundant in urban and industrial environments and potentially serve as one of the primary precursors for new particle formation (NPF). Pi-pi stacking is a distinctive weak interaction observed between aromatic compounds. Aromatic oxygenated organic molecules (AOOM) are key products of atmospheric oxidation of aromatic compounds; however, the role of pi-pi stacking in their involvement in atmospheric new particle formation (NPF) remains unclear. This study used quantum chemical calculations to reveal the nucleation mechanism of AOOM through pi-pi stacking and hydrogen bonding. The results indicate that the contribution of pi-pi stacking to nucleation in aromatic compounds is primarily determined by the stacking area. For aromatic hydrocarbons with 1–2 phenyl groups, the Gibbs free energy (ΔG) of dimolecular clusters formed solely by pi-pi stacking is positive. In contrast, for polycyclic aromatic hydrocarbons with three or more phenyl groups, the ΔG of these clusters decreases significantly and becomes negative. Single-phenyl AOOM primarily participates in the NPF process through hydrogen bonding with sulfuric acid molecules. In this work, an explanation is provided for observations and laboratory findings of the appearance of aromatic-ring-retaining species in nanoparticles. The discovery of pi-pi stacking also completes the variety of atmospheric nucleation weak interactions. The oxidation and nucleation mechanisms of aromatic compounds should be reassessed, considering the effects of pi-pi stacking, especially polycyclic aromatic hydrocarbons. These findings have important implications for sustainable urban air-quality management. By clarifying the role of pi-pi stacking, particularly in polycyclic aromatic hydrocarbons, this study may improve predictions of new particle formation, refine secondary organic aerosol modeling, and inform targeted emission-control policies to protect public health and mitigate climate impacts. Full article

Polymer insulation layers such as polyimide (PI) have gradually replaced inorganic dielectric layers (SiO₂, SiCN) in the integrated packaging process of hybrid bonding (HB). PI can fill the gaps in the thermal compression bonding process and help to obtain a good Cu/Polymer bonding interface. At present, the existing post-crack double cantilever beam tensile test (PBC-DCB) has been successfully applied to the quantitative measurement of bonding strength of hybrid bonding with inorganic materials, but this method only considers elastic behavior. Since PI exhibits viscidity, elasticity and plasticity, knowing how to correlate these properties to the bonding process is challenging. Whether PBC-DCB is suitable for the characterization of PI bonding is unclear. This paper presents a comprehensive experimental and finite element analysis (FEA) study on the PI–PI bonding interface. Firstly, nanoindentation experiments and simulations are performed on the prepared PI interface to obtain key elasticity and plasticity parameters. Then, the bonding strength is characterized by the PBC-DCB test. Theoretical and experimental results show that the plasticity of PI causes energy dissipation during stretching, resulting in a deviation of approximately 2.51% compared with pure elasticity. Based on experimental data, the Cohesive Zone Model (CZM) FEA method is used to simulate the crack propagation. The results indicate that the Embedded Process Zone (EPZ) model can accurately describe crack initiation and delamination behavior, with a margin of error of about 3.61%. Finally, based on the EPZ CZM, defects such as bonding void and wafer warpage are further discussed in relation to bonding strength measurement. Full article

The metallogelation process has been successfully achieved by utilizing a crystal engineering approach to generate a new metallogel. While the coordination of metal ions to ligands plays a very important role for building the primary structure, the stabilization and morphology of metallogels are heavily dependent on various intra-molecular interactions and non-covalent interactions, with hydrogen bonding (HB) often playing a dominant and structurally organizing role. In the present study, gelation experiments were achieved successfully by reacting vanadium acetylacetonate with a hydrazone ligand using different solvents. The metallogel shows excellent gelation ability with 1.7 wt% minimum gelator concentrations and the gel–sol dissociation temperature, T_gel is 55 °C (water/methanol). The structural properties of the metallogel were studied using single-crystal X-ray crystallography. The crystal structure analysis of the metallogel shows the presence of various interactions such as hydrogen bonding, pi–pi interactions, pnictogen bonding, and other weak non-covalent interactions. These molecular interactions play a very important role in the gelation process and also affect the gel’s properties like swelling behavior, viscosity, and elasticity. Full article

Background: Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobic, immobile oral bacterium responsible for the secretion of virulence factors, namely leukotoxin (LtxA), a large exotoxin of the RTX family that enables the bacterium to evade the immune system by destroying leukocytes, resulting in aggressive periodontitis (AP) leading to tooth loss. Methods: This study aimed to screen 106 molecules derived from Moroccan propolis in order to identify potential inhibitors of the active sites of LtxA based on molecular docking, ADMET property evaluation, and molecular dynamics (MD) simulation. Results: Epigallocatechin gallate (EGCg), used as a reference compound, showed binding energies of −6.9 kcal/mol, −6.1 kcal/mol, −6.5 kcal/mol, and −5.9 kcal/mol with the four active sites P1, P2, P3, and P4, respectively. By establishing conventional hydrogen bonds, pi-alkyl bonds, and non-covalent pi–pi bonds. Chrysin and luteolin showed favorable binding affinities with the four active sites, named as follows: P1–P4 (P1–chrysin = −7.5 kcal/mol; P2–chrysin = −7.9 kcal/mol; P3–chrysin = −8.1 kcal/mol; P4–chrysin = −6.9 kcal/mol; P1–luteolin = −7.3 kcal/mol; P2–luteolin = −7.6 kcal/mol; P3–luteolin = −8.1 kcal/mol; P4–luteolin = −7.3 kcal/mol). The binding affinity of these two propolis derivatives was stabilized by pi−sigma bonds, pi−alkyl bonds, conventional hydrogen bonds, pi-cation interactions, non-covalent pi–pi bonds, and carbon–hydrogen bonds. According to free energy calculations performed with Prime MM-GBSA, the complexes formed by chrysin demonstrated the most stable interactions due to Van der Waals and lipophilic forces. Luteolin formed significant interactions, but slightly weaker than those of chrysin. These results reveal the inhibitory potential of chrysin and luteolin with protein active sites. MD simulations corroborated the excellent stability of complexes formed by chrysin, as indicated by low RMSD values, suggesting favorable dynamic behavior. Conclusions: These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations. Full article

This study explores the potential of two marine-derived bacteria, Cytobacillus kochii and Marinobacter, through in silico analysis of their catechol 2,3-dioxygenase (C23O) enzymes. Molecular docking simulations were conducted using AutoDock Vina to assess the binding interactions between C23O enzymes and ten hydrocarbon pollutants, including monocyclic and polycyclic aromatic hydrocarbons (PAHs). Binding affinities ranged from −4 to −8.7 kcal/mol for Cytobacillus kochii, with the highest affinity observed for fluoranthene (−8.7 kcal/mol), followed by pyrene (−8.5 kcal/mol) and phenanthrene (−8.2 kcal/mol). In comparison, Marinobacter’s C23O showed binding affinities between −4.1 and −8 kcal/mol, with fluoranthene (−8 kcal/mol) and phenanthrene (−7.9 kcal/mol) being top performers. Despite slightly lower affinity, Marinobacter exhibits superior environmental resilience under high salinity and temperature, making it valuable for application in fluctuating marine conditions. Structural interaction analysis revealed consistent pi-pi stacking and hydrogen bonding within the active sites, further supporting enzyme–substrate compatibility. These computational findings underscore Cytobacillus kochii ’s superior catalytic potential and Marinobacter’s ecological robustness. The integration of both strains into a microbial consortium offers a promising synergistic approach, combining enzymatic efficiency and environmental adaptability for effective hydrocarbon degradation. While these computational assessments offer valuable predictive insights, further validation through in vitro and in vivo experiments would be beneficial to determine the actual hydrocarbon degradation efficiencies. Full article

Diabetes is a chronic metabolic disorder characterized by persistently high blood glucose levels due to insulin malfunction, defective insulin secretion, or both. Chromen-4-one, known to have diverse biological activity, is a core structure found in many natural products, particularly in the flavonoid and isoflavonoid families. The study aims to explore the potential of Chrome-4-one derivatives as a potential antidiabetic agent through the α-glucosidase inhibition mechanism. The compounds were retrieved from the PubChem database, optimized, and prepared using ChemDraw 12.0, Spartan14, and UCSF Chimera. The post-docking analysis was performed using BIOVIA Discovery Studio. Theoretical oral bioavailability and toxicity predictions were performed using ADMETlab3.0. Molecular docking of the compounds against the α-glucosidase enzyme (PDB ID: 3A4A) was carried out using AutoDock Vina 1.2.5. According to Lipinski’s rule of five (5), all the ligands passed the oral bioavailability and are druggable. The binding score of all the ligands was better than the native ligand (−5.7 Kcal/mol) but slightly lower than that of Acarbose (−9.0 Kcal/mol), except for L7 (Myricetin), which equals the standard drug. The ligands revealed good interaction with the enzyme’s active site residues. The most notable interactions were hydrogen bonding, van der Waals, Pi–anion, Pi–cation, Pi–Pi T-shape, Pi–Sigma, and carbon–hydrogen bonds. The ligands interacted with the key catalytic residues: Asp352, Glu277, Glu411, Trp158, and Arg442, which are responsible for α-glucosidase inhibition. The result of the study suggests that the chrome-4-one derivatives have the potential to be utilized as a lead molecule for orally available α-glucosidase inhibitors. Full article

Microrobot navigation in constrained environments requires path planning methods that ensure both efficiency and collision avoidance. Conventional approaches, which typically combine graph-based path finding with geometric path simplification, effectively reduce path complexity but often generate collision-prone paths because wall boundaries are not considered during simplification. Therefore, to overcome this limitation, we present Secure Angle-based Geometric Elimination (SAGE), a single-pass path-simplification algorithm that converts pixel-level shortest paths into low-complexity trajectories suitable for real-time collision-free navigation of microrobots. SAGE inspects consecutive triplets (p_i, p_i+1, p_i+2) and removes the middle point when the turning angle is smaller than threshold (∠p_ip_i+1p_i+2 ≤ θ_th) or the direct segment (p_i → p_i+2) is collision-free. Quantitative analysis shows that SAGE achieves approximately 5% shorter path length, 20% lower turning cost and 0% collision rate, while maintaining computation comparable to the Ramer–Douglas–Peucker algorithm. Integration with Dijkstra and RRT planners confirms scalability across complex maze and vascular environments. Experimental microrobot demonstrations show navigation with complete collision avoidance, establishing SAGE as an efficient and reliable framework for high-speed microrobot navigation and automation in lab-on-a-chip, chemical-reaction and molecular-diagnostic systems. Full article

The use of carbon fiber-reinforced polymer (CFRP) tubes as crash boxes has become a subject of interest due to their high specific strength and energy absorption capabilities. This study investigates the crashworthiness performance of rectangular tubes made of CFRP, with and without holes and polyurethane foam (PUF)-filled inner structures. The designed tubes were subjected to quasi-static axial compression loading. In addition to carefully documenting failure histories, data on crash load and displacement responses were methodically recorded during testing. To evaluate crashworthiness performance, three design parameters were considered: hole diameter, the number of holes in both the x and y directions, and whether the tube was filled with foam or left unfilled. Machine learning (ML) was also used to reduce the time and cost by predicting the crashworthiness indicators of the tubes from fewer experiments. A collection of ML algorithms such as decision tree regressor (DTR), linear regressor (LR), ridge regressor (RR), lasso regressor (LAR), elastic nets (ENs), and multi-layer perceptron (MLP) have been utilized to predict crashworthiness indicators such as initial peak force (P_ip), mean crushing force (P_m) and energy absorption (EA) of the design tubes from the experimental data. The experimental results showed that PUF-filling significantly enhanced crashworthiness properties, with P_m and EA increasing by nearly threefold compared to unfilled tubes. Furthermore, in unfilled tubes, the introduction of holes led to varying effects depending on the hole diameter and placement. Meanwhile, in PUF-filled tubes, the presence of holes reduced the crashworthiness performance. For ML prediction, the DTR achieved the best accuracy with the lowest value of root mean squared error (RMSE) and mean absolute percentage error (MAPE) of 1251 and 11.37%, respectively. These findings demonstrate both the importance of PUF-filled, perforation configurations and the feasibility of ML models in optimizing CFRP crash box designs. Full article

Pseudomonas aeruginosa is an opportunistic pathogen commonly associated with infections in hospitalized and immunocompromised patients due to its virulence and antimicrobial resistance. In the poultry industry, it has been associated with hatchery mortality. This study aimed to characterize P. aeruginosa isolated from pipped eggs, one-day-old chicks, and broiler carcasses obtained from a slaughterhouse in São Paulo state, Brazil. Nineteen strains of P. aeruginosa were selected and their virulence genes were amplified via PCR. Clonality analysis was performed using BOX-PCR, and three strains were selected for whole-genome sequencing (WGS). All isolates carried aprA, plcH, plcN, lasA, lasB, lasI, lasR, rhlAB, and phzH. The exoA gene was detected in 73.7% of strains, while algD was present in 21.1%. The exoY and exoT genes were present in 94.7% of strains (18/19), whereas exoS was present in 47.4% (9/19). None of the isolates harbored the exoU gene. BOX-PCR and phylogenetic analyses revealed diverse clonal patterns. The sequenced strains were classified as O3 ST116, O2 ST1649, and O3 ST1744. The presence of virulence and antimicrobial resistance determinants in poultry-associated strains underscores the need for surveillance, as these isolates may represent a source for transmission of P. aeruginosa to humans. Our findings highlight the importance of monitoring P. aeruginosa within poultry production and emphasize the value of genomic approaches to understand its diversity, evolution, and public health risks. Full article

This paper presents an enhanced operation strategy for a recently proposed converter called Modified Non-Inverting Step-Down/Up (MNI-SDU) DC-DC converter intended for battery voltage regulation. Unlike the conventional approach, where both switching stages share a single duty cycle, the proposed method controls asynchronously the two duty cycles through a fixed time offset to optimize performance. A methodology is developed to define suitable duty cycle ranges that ensure proper converter operation according to input/output voltage specifications, while simultaneously reducing the current and voltage ripples and electrical stress in the capacitor and semiconductors. Furthermore, a model-based control strategy is proposed, taking into account the enhanced operational characteristics. Consequently, a PI-PI current-mode controller is designed using loop shaping techniques to maintain the output voltage regulated at the desired level. The proposed approach is analyzed mathematically and validated through experimental results. The findings demonstrate that optimizing through asynchronous duty-cycle control with a fixed time offset improves ripple, stress values, and overall efficiency, while maintaining robust output voltage regulation, making this method well-suited for applications requiring compact and reliable power conversion. Full article

This paper investigates the influence of initial porosity and its evolution on the mechanical behavior of metallic materials manufactured by additive manufacturing (AM), using the Gurson model to predict the initiation and propagation of damage in specimens produced via Laser Powder Bed Fusion (LPBF). The methodology combines experimental uniaxial tensile tests, numerical simulations based on the Gurson model, and the parametric identification method (PIP) to calibrate constitutive parameters (${\sigma }_{y0}$, ${\sigma }_{\infty }$, $\delta$, $\xi$). The specimens, made of AlSi10Mg with different printing directions (horizontal and vertical) and porosity levels, were evaluated to determine the relationship between density, anisotropy, and mechanical properties. The experimental results revealed that vertical printing accelerates fracture due to the concentration of stresses at the interfaces between layers, while the numerical simulations, compared with the von Mises model, showed greater accuracy of the Gurson model in predicting damage in porous materials. The analysis of porosity evolution highlighted the impact of void size and spacing on coalescence and ductility. The proposed methodology was validated, establishing a useful approach for evaluating the mechanical behavior of materials manufactured by AM. This work contributes to the advancement of the design of lightweight and resistant components, with applications in sectors such as aerospace and automotive, and suggests directions for future studies, including the investigation of other alloys and dynamic loading conditions. Full article

Intrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g., phosphorylation), enabling dynamic intermolecular interactions through conformational plasticity. Furthermore, IDRs drive liquid–liquid phase separation (LLPS) of biomacromolecules via multivalent interactions such as electrostatic attraction and pi–pi interactions, generating biomolecular condensates that are essential throughout the cellular lifecycle. These condensates separate intracellular space, forming a physical barrier to avoid interference between other molecules, thereby improving reaction specificity and efficiency. As a dynamically equilibrated process, LLPS formation and maintenance are regulated by multiple factors, endowing the condensates with rapid responsiveness to environmental cues and functional versatility in modulating diverse signaling cascades. Consequently, disruption of LLPS homeostasis can derail its associated biological processes, ultimately contributing to disease pathogenesis. Moreover, precisely because liquid–liquid phase separation (LLPS) is co-regulated by multiple factors, it may provide novel insights into the pathogenic mechanisms of disorders such as autism spectrum disorder (ASD), which result from the cumulative effects of multiple etiological factors. Full article

PDE11A is a little-studied phosphodiesterase sub-family that breaks down cAMP/cGMP, with the PDE11A4 isoform enriched in the memory-related hippocampal formation. Age-related increases in PDE11A expression occur in human and rodent hippocampus and cause age-related cognitive decline of social memories. Interestingly, age-related increases in PDE11A4 protein ectopically accumulate in spherical clusters that group together in the brain to form linear filamentous patterns termed “PDE11A4 ghost axons”. The biophysical/physiochemical mechanisms underlying this age-related clustering are not known. Here, we determine if age-related clustering of PDE11A4 reflects liquid–liquid phase separation (LLPS; biomolecular condensation), and if PDE11A inhibitors can reverse this LLPS. We show human and mouse PDE11A4 exhibit several LLPS-promoting sequence features, including intrinsically disordered regions, non-covalent pi–pi interactions, and prion-like domains that were particularly enriched in the N-terminal regulatory region. Further, multiple bioinformatic tools predict PDE11A4 undergoes LLPS. Consistent with these predictions, aging-like PDE11A4 clusters in HT22 hippocampal neuronal cells were membraneless spherical droplets that progressively fuse over time in a concentration-dependent manner. Deletion of the N-terminal intrinsically disordered region prevented PDE11A4 LLPS despite equal protein expression between WT and mutant constructs. 1,6-hexanediol, along with tadalafil and BC11-38 that inhibit PDE11A4, reversed PDE11A4 LLPS in HT22 hippocampal neuronal cells. Interestingly, PDE11A4 inhibitors reverse PDE11A4 LLPS independently of increasing cAMP/cGMP levels via catalytic inhibition. Importantly, orally dosed tadalafil reduced PDE11A4 ghost axons in old mouse ventral hippocampus by 50%. Thus, PDE11A4 exhibits the four defining criteria of LLPS, and PDE11A inhibitors reverse this age-related phenotype both in vitro and in vivo. Full article

Recent bioassay studies have unexpectedly supported the high (computationally predicted) binding affinities of angiotensin receptor blockers (ARBs) at α-adrenergic receptors (αARs) in isolated smooth muscle. Computational predictions from ligand docking studies are consistent with very low concentrations of ARBs (e.g., sartans or bisartans) that partially reduce (20–50%) the contractile response to phenylephrine, suggesting that some ARBs may function as partial inverse agonists at αARs. Virtual ligand screening (docking) and molecular dynamics (MD) simulations were carried out to explore the binding affinities and stabilities of selected non-peptide ligands (e.g., ARBs and small-molecule opioids) for several G-protein coupled receptor (GPCR) types, including angiotensin II (AngII) type 1 receptor (AT₁R), α1AR, α2AR, and μ-(µOR) and ժ-opioid receptors (ժOR). Results: All ligands docked preferentially to the binding pocket on the cell surface domain of the GPCR types investigated. Drug binding was characterized by weak interactions (hydrophobic, hydrogen bonding, pi-pi) and stronger ionic and salt-bridge interactions (cation-pi and cation-anion interactions). Ligands specific to each GPCR category showed considerable cross-binding with alternative GPCRs, with small-molecule medications appearing less selective than their peptide or ARB functional equivalents. ARBs that exhibit higher affinities for AT₁R also demonstrate higher affinities for µORs and ժORs than opiate ligands, such as fentanyl and naltrexone. Moreover, ARBs had a higher affinity for αARs than either alpha agonists (epinephrine and phenylephrine) or inhibitors (prazosin and doxazosin). MD simulations of membrane-embedded ARB-GPCR complexes proved stable over nanosecond time scales and suggested that some ARBs may behave as agonists or antagonists depending on the GPCR type. Based on the results presented in this and related investigations, we propose that agonists bind to the resting A-site of GPCRs, while inverse agonists occupy the desensitizing D-site, which partial agonists like morphine and fentanyl share, contributing to addiction. ARBs block both AngII and alpha receptors, suggesting that they are more potent antihypertensive drugs than ACE inhibitors. ARBs have the potential to inhibit morphine tolerance and appear to disrupt receptor desensitization processes, potentially by competing at the D-site. Our results suggest the possible therapeutic potential of ARBs in treating methamphetamine and opiate addictions. Full article

Proteins regulate various cellular processes and are of great biological interest. The protein search engine is a crucial tool in proteomics research, used to analyze high-throughput tandem mass spectrometry data and to identify protein sequence information. A core step in protein search engines is constructing sequence tag indexes and performing the rapid retrieval of protein databases. However, as the scale of protein sequence data continues to grow, traditional protein search engines face the dual challenges of the high storage cost of sequence tag indexes and low retrieval efficiency. To address these issues, we propose a sequence tag index scheme named STIP, which is based on an inverted index and compression techniques. Based on STIP, we design a peptide retrieval algorithm named STIP-Search. This algorithm utilizes the sequence tag index constructed by STIP for peptide sequence retrieval. STIP uses the greedy algorithm to partition the tag index into blocks; in this way, STIP can generate tag indexes for very large protein databases, such as NCBI-nr. Compared to the current four mainstream tag index generation algorithms used in Open-pFind, MODplus, TIIP and PIPI2, STIP has the lowest storage and time consumption. It utilizes delta encoding, index reduction, and dynamic bit width encoding to compress the tag index, reducing the storage cost by 76.2%. Compared to TIIP, which is currently the algorithm with the lowest time complexity, the time cost of the peptide sequence retrieval of STIP-Search is reduced by 8.94% to 23.31%. Full article