Search Results (48)

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Aerospace engines ingest small particles when operating in a particulate-rich environment, such as sandstorms, atmospheric pollution, and volcanic ash clouds. These micron particles enter their cooling channels, leading to film-cooling hole blockage and thus thermal damage to turbine blades made of nickel-based single-crystal superalloy materials. This work studied the collision and deposition mechanisms between the micron particles and structure surface. A combined theoretical and numerical study was conducted to investigate the effect of deposits on particle collision and deposition. Finite element models of deposits with flat and rough surfaces were generated and analyzed for comparison. The results show that the normal restitution coefficient is much lower when a micron particle impacts a deposit compared to that of particle collisions with DD3 nickel-based single-crystal wall surfaces. The critical deposition velocity of a micron particle is much higher for particle–deposit collisions than for particle–wall collision. The critical deposition velocity decreases with the increase in particle size. When micron particles deposit on the wall surface of the structure, early-stage particle–wall collision becomes particle–deposit collision when the height of the deposits is greater than twice the particle diameter. For contact between particles and rough surface deposits, surfaces with a shorter correlation length, representing a higher density of asperities and a steeper surface, have a much longer contact time but a lower contact area. The coefficient of restitution of the particle reduces as the surface roughness of the deposits increase. The characteristic length of the roughness has little effect on the rebounding rotation velocity of the particle. Full article

Industrial biotechnology offers a potential ecological solution for PET recycling under relatively mild reaction conditions via enzymatic degradation, particularly using the leaf branch compost cutinase (LCC) quadruple mutant ICCG. To improve the efficient downstream processing of this biocatalyst after heterologous gene expression with a suitable production host, protein crystallization can serve as an effective purification/capture step. Enhancing protein crystallization was achieved in recent studies by introducing electrostatic (and aromatic) interactions in two homologous alcohol dehydrogenases (Lb/LkADH) and an ene reductase (NspER1-L1,5) produced with Escherichia coli. In this study, ICCG, which is difficult to crystallize, was utilized for the application of crystal contact engineering strategies, resulting in ICCG mutant L50Y (ICCGY). Previously focused on the Lys-Glu interaction for the introduction of electrostatic interactions at crystal contacts, the applicability of the engineering strategy was extended here to an Arg-Glu interaction to increase crystallizability, as shown for ICCGY T110E. Furthermore, the rationale of the engineering approach is demonstrated by introducing Lys and Glu at non-crystal contacts or sites without potential interaction partners as negative controls. These resulting mutants crystallized comparably but not superior to the wild-type protein. As demonstrated by this study, crystal contact engineering emerges as a promising approach for rationally enhancing protein crystallization. This advancement could significantly streamline biotechnological downstream processing, offering a more efficient pathway for research and industry. Full article

Protein crystallization is an alternative to well-established but cost-intensive and time-consuming chromatography in biotechnological processes, with protein crystallization defined as an essential unit operation for isolating proteins, e.g., active pharmaceutical ingredients. Crystalline therapeutic proteins attract interest in formulation and delivery processes of biopharmaceuticals due to the high purity, concentration, and stability of the crystalline state. Although improving protein crystallization is mainly achieved by high-throughput screening of crystallization conditions, recent studies have established a rational protein engineering approach to enhance crystallization for two homologous alcohol dehydrogenases from Lactobacillus brevis (LbADH) and Lactobacillus kefiri (LkADH). As generalizing crystallization processes across a wide range of target proteins remains challenging, this study takes a further step by applying the successful crystal contact engineering strategies for LbADH/LkADH to a non-homologous protein, an NADH-binding derivative of the Nostoc sp. PCC 1720 ene reductase (NspER1-L1,5). Here, the focus lies on introducing electrostatic interactions at crystal contacts, specifically between lysine and glutamic acid. Out of the nine tested NspER1-L1,5 mutants produced in E. coli, six crystallized, while four mutants revealed an increased propensity to crystallize in static µL-batch crystallization compared to the wild type: Q204K, Q350K, D352K, and T354K. The best-performing mutant Q204K was selected for upscaling, crystallizing faster than the wild type in a stirred batch crystallizer. Even when spiked with E. coli cell lysate, the mutant maintained increased crystallizability compared to the wild type. The results of this study highlight the potential of crystal contact engineering as a reliable tool for improving protein crystallization as an alternative to chromatography, paving the way for more efficient biotechnological downstream processing. Full article

Nowadays, induction motors are an essential part of industrial development. Faults due to short-circuit turns within induction motors are “incipient faults”. This type of failure affects engine operation through undesirable vibrations. Such vibrations negatively affect the operation of the system or the products with which said motor is in contact. Early fault detection prevents sudden downtime in the industry that can result in heavy economic losses. The incipient failures these motors can present have been a vast research topic worldwide. Existing methodologies for detecting incipient faults in alternating current motors have the problem that they are implemented at the simulation level, or are invasive, or do not allow in situ measurements, or their digital implementation is complex. This article presents the design and development of a purpose-specific system capable of detecting short-circuit faults in the turns of the induction motor winding without interrupting the motor’s working conditions, allowing online measurements. This system is standalone, portable and allows non-invasive and in situ measurements to obtain phase currents. These data form classified descriptors using a multilayer perceptron neural network. This type of neural network enables agile and efficient digital processing. The developed neural network could classify current faults with an accuracy rate of 93.18%. The neural network was successfully implemented on a low-cost and low-range purpose-specific Field Programmable Gate Array board for online processing, taking advantage of its computing power and real time processing features. The measurement of phase current and the class of fault detected is displayed on a liquid-crystal display screen, allowing the user to take necessary actions before major faults occur. Full article

In this study, unconventional C—Hlg···H–C (Hlg = Cl, Br, and I) interactions involving sp, sp², and sp³ organic halides were investigated at the RI-MP2/aug-cc-pVQZ level of theory. Energy Decomposition Analyses (EDA) and Natural Bonding Orbital (NBO) studies showed that these intermolecular contacts are mainly supported by orbital and dispersion contributions, which counteracted the unfavorable/slightly favorable electrostatics due to the halogen–hydrogen σ-hole facing. In addition, the Bader’s Quantum Theory of Atoms in Molecules (QTAIM) and the Noncovalent Interaction plot (NCIplot) visual index methodologies were used to further characterize the interactions discussed herein. We expect that the results reported herein will be useful in the fields of supramolecular chemistry, crystal engineering, and rational drug design, where the fine tuning of noncovalent interactions is crucial to achieve molecular recognition or a specific solid-state architecture. Full article

(1) Background: PETG (polyethylene terephthalate glycol) is a transparent, inexpensive, and versatile thermoplastic biomaterial, and it is increasingly being used for a variety of medical applications in dentistry, orthopedics, tissue engineering, and surgery. It is known to have remarkable properties such as tensile strength, high ductility, and resistance to chemical insults and heat, but it can be affected by various environmental conditions. The aim of the present study was to evaluate the topographical characteristics of four thermoplastic dental appliance materials in relation to water sorption in simulated oral environments (artificial saliva samples with different pH values). (2) Methods: The following four types of PETG clear thermoplastic materials were selected for the present study: Leone (L), Crystal (C), Erkodur (E), and Duran (D). In relation to the desiccation and water-uptake stages, their water sorption (Wsp) and solubility (Wsl) were calculated, and the surface topographies were analyzed on two length scales. The surface roughness was determined using a contact profilometer, and nanoroughness measurements were generated by three-dimensional profiles using an atomic force microscope (AFM). Statistical analyses (one-way ANOVA and unpaired and paired Student t-tests) were performed. (3) Results: After saliva immersion, the weights of all samples increased, and the highest sorption was recorded in a basic environment. Among the materials, the water uptake for the L samples was the highest, and for E, it was the lowest. In relation to water solubility, significant values were registered for both the L and C samples’ materials. After immersion and desiccation, a decreasing trend in microroughness was observed. The AFM high-resolution images reflected more irregular surfaces related to saliva immersion. (4) Conclusions: The sorption rates recorded in water-based artificial saliva were higher for basic pH levels, with significant differences between the samples. There were also significant differences related to the behaviors of the materials included in the study. In relation to roughness, on a microscale, the surfaces tended to be smoother after the saliva immersions, and on a nanoscale, they became more irregular. Full article

A series of novel salts of heterocyclic polyamines with 5-sulfosalicylic acid (C₄H₇N₄⁺)(C₇H₅O₆S⁻)∙2(H₂O) (1), (C₄H₆ClN₄⁺)(C₇H₅O₆S⁻)∙H₂O (2), (C₅H₈N₃⁺)(C₇H₅O₆S⁻)∙H₂O (3), (C₅H₇N₆⁺)(C₇H₅O₆S⁻)∙H₂O (4), (C₆H₁₄N₂²⁺)(C₇H₄O₆S²⁻)∙H₂O (5), and (C₁₄H₁₉N₂⁺)(C₇H₅O₆S⁻) (6) have been successfully synthesized. Their crystal structures have been determined by single-crystal X-ray diffraction. Overall, compounds adopt a layered structure with aminium cations and 5-sulfosalicylic anions linked via water molecules. The solid-state architectures of these compounds are dominated by O(N,H)-H⋯O and N-H⋯N hydrogen bonds and stabilized by weak interconnects. C-Cl⋯π and S-O⋯π interactions, apart from π⋯π and C-H(O)⋯π, were reported. Diverse approaches were used to study the effect of substituents in the polyamines in solid-state arrangement. A Hirshfeld surface analysis, with associated 3D Hirshfeld surface maps and 2D fingerprint plots, molecular electrostatic potential, and energy frameworks were used to comprehensively investigate the nature and hierarchy of non-covalent interactions and inspect supramolecular differences. The contact enrichment ratio calculations provided deeper insight into the propensity of interconnects to influence crystal packing. The evaluation of the effects of H-bonding synthons resulting from different substituents in the polyamines on self-assemblies is also presented. In the context of crystal engineering, a specific intramolecular synthon via O-H⋯O observed in nearly all crystals can be employed in the pseudo-cyclic replacement strategy in the design of new molecules. Full article

Cracks and crack-like defects in engineering structures have greatly reduced the structural strength. An interface crack with one contact area in a combined tension–shear field of decagonal quasicrystal bi-material is investigated. Based on the deformation compatibility equation and displacement potential function, the complex representation of stress and displacement is given. Using the mixed boundary conditions, the closed-form expressions for the stresses and the displacement jumps in the phonon field and phason field on the material interface are obtained. The results show that the stress intensity factor at the crack tip is zero for the phason field. The variation in the stress intensity factor and the length of the contact zone in the phonon field is given, and the result is consistent with the properties of the crystal. The design of safe engineering structures and the formulation of reasonable quality acceptance standards may benefit from the theoretical research carried out here. Full article

3-chloro-4-hydroxyphenylacetic acid (CHPAA) is a fungal metabolite. It is a small molecule that is useful in crystal engineering studies due to the functional groups present. Six amines were selected to form salts with CHPAA. Linear derivatives included diethylamine (DEA) and di-N-butylamine (DBM). The aromatic compounds chosen were 2-aminopyridine (A2MP), 2-amino-4-methylpyridine (A24MP), 2-amino-6-methylpyridine (A26MP) and 4-dimethylaminopyridine (DMAP). The salts were characterised using single-crystal X-ray diffraction, thermal analysis, FTIR spectroscopy and Hirshfeld surface analysis. For all the crystal structures, N-H···O and C-H···Cl contacts were present. O-H···O contacts were found in all the crystal structures except for ($CHPA{A}^{2-})\left(2DE{A}^{+}\right)$, which was also the only structure that displayed a Cl···Cl contact. Furthermore, C-H···O contacts were found in all the crystal structures except for $(CHPA{A}^{-})(DB{M}^{+}).$The thermal stability trend showed that the DBM salt was more stable than the DEA salt. For the aromatic co-formers, the thermal stability trend showed the following: $\left(CHPA{A}^{-}\right)(DMA{P}^{+})$>$(CHPA{A}^{-})(A2M{P}^{+})>\left(2CHPA{A}^{-}\right)\left(2A26M{P}^{+}\right)>(CHPA{A}^{-})(A24M{P}^{+})$. Full article

Though originally characterized as an inactive or transcriptionally repressive factor, the NF-κB p50 homodimer has become appreciated as a physiologically relevant driver of specific target gene expression. By virtue of its low affinity for cytoplasmic IκB protein inhibitors, p50 accumulates in the nucleus of resting cells, where it is a binding target for the transcriptional co-activator IκBζ. In this study, we employed X-ray crystallography to analyze the structure of the p50 homodimer on κB DNA from the promoters of human interleukin-6 (IL-6) and neutrophil-gelatinase-associated lipocalin (NGAL) genes, both of which respond to IκBζ. The NF-κB p50 homodimer binds 11-bp on IL-6 κB DNA, while, on NGAL κB DNA, the spacing is 12-bp. This begs the question: what DNA binding mode is preferred by NF-κB p50 homodimer? To address this, we engineered a “Test” κB-like DNA containing the core sequence 5′-GGGGAATTCCCC-3′ and determined its X-ray crystal structure in complex with p50. This revealed that, when presented with multiple options, NF-κB p50 homodimer prefers to bind 11-bp, which necessarily imposes asymmetry on the complex despite the symmetry inherent in both the protein and its target DNA, and that the p50 dimerization domain can contact DNA via distinct modes. Full article

With the advancement of information display technologies, research on liquid crystals is undergoing a tremendous shift to photonic devices. For example, devices and configurations based on liquid crystal materials are being developed for various applications, such as spectroscopy, imaging, and fiber optics. One of the problems behind the development of photonic devices lies in the preparation of patterned surfaces that can provide high resolution. Among all liquid crystal alignment techniques, photoalignment represents a promising non-contact method for the fabrication of patterned surfaces. In this review, we discuss the original research findings on electro-optic effects, which were mainly achieved at the Department of Electronic and Computer Engineering of the Hong Kong University of Science and Technology and the collaborating research laboratories. Full article

In order to address the issue of vibration, it is crucial to accurately measure the vibration distribution. The authors previously developed the one-pitch phase analysis (OPPA) method, which allows for rapidly capturing the three-dimensional shape of a flat object. By integrating this method into a system, an OPPA vibration distribution measurement system was created, utilizing a line light source consisting of LEDs or optical fibers and also a high-speed camera to measure the vibrations of three-dimensional objects without physical contact. To further extend the application of the OPPA method to larger objects, such as cars, in this paper, a new system is introduced using a commercially available projector using a liquid crystal display (LCD) instead of a liner light source and a glass grating. This new system, which employs an ultra-short throw projector, is highly sensitive in displacement measurements and provides a wide-area analysis. These kinds of projectors produce noises at the frequency of the cooling fan and the refresh rate of the LCD. However, in this study, these noise sources were also examined. The capabilities of the new system are demonstrated through its application to the measurement of vibrations in a car door and an engine head. The measurement system and examples of its application are presented. Full article

An extremely small proportion of the X-ray crystal structures deposited in the Protein Data Bank are of RNA or RNA–protein complexes. This is due to three main obstacles to the successful determination of RNA structure: (1) low yields of pure, properly folded RNA; (2) difficulty creating crystal contacts due to low sequence diversity; and (3) limited methods for phasing. Various approaches have been developed to address these obstacles, such as native RNA purification, engineered crystallization modules, and incorporation of proteins to assist in phasing. In this review, we will discuss these strategies and provide examples of how they are used in practice. Full article

To meet aero-engine aluminum skirt requirements, an experiment was carried out using Al–Nb–B₂O₃–CuO as the reaction system and a 6063 aluminum alloy melt as the reaction medium for a contact reaction, and 6063 aluminum matrix composites containing in situ particles were prepared with the near-liquid-phase line-casting method after the reaction was completed. The effects of the reactant molar ratio and the preheating temperature on the in situ reaction process and products were explored in order to determine the influence of in situ-reaction-product features on the organization and the qualities of the composites. Thermodynamic calculations, DSC analysis, and experiments revealed that the reaction could continue when the molar ratio of the reactants of Al–Nb–B₂O₃–CuO was 6:1:1:1.5. A kinetic study revealed that the Al thermal reaction in the system produced Al₂O₃ and [B], and the [B] atoms interacted with Nb to generate NbB₂. With increasing temperature, the interaction between the Nb and the AlB₂ produced hexagonal NbB₂ particles with an average longitudinal size of 1 μm and subspherical Al₂O₃ particles with an average longitudinal size of 0.2 μm. The microstructure of the composites was reasonably fine, with an estimated equiaxed crystal size of around 22 μm, a tensile strength of 170 MPa, a yield strength of 135 MPa, an elongation of 13.4%, and a fracture energy of 17.05 × 10⁵ KJ/m³, with a content of 2.3 wt% complex-phase particles. When compared to the matrix alloy without addition, the NbB₂ and Al₂O₃ particles produced by the in situ reaction had a significant refinement effect on the microstructure of the alloy, and the plasticity of the composite in the as-cast state was improved while maintaining higher strength and better overall mechanical properties, allowing for industrial mass production. Full article