Search Results (252)

Promoting the development of aerospace vehicles toward structural–functional integration and intelligent sensing is a key strategy for achieving lightweight, high-reliability, and autonomous operation and maintenance of next-generation aircraft. However, traditional external sensors face significant limitations because of their bulky size, installation challenges, and incompatibility with aerodynamic surfaces. These issues are particularly pronounced on complex, high-curvature substrates, where achieving conformal bonding is difficult, thus restricting their application in critical components. In this study, aerosol jet printing (AJP) was employed to directly fabricate silver nanoparticle-based temperature sensors with real-time monitoring capabilities on the surface of high-curvature stainless steel sleeves, which serve as typical engineering components. This approach enables the in situ manufacturing of high-precision conformal sensors. Through optimized structural design and thermal treatment, the sensors exhibit reliable temperature sensitivity. Microscopic characterization reveals that the printed sensors possess uniform linewidths and well-defined outlines. After gradient sintering at 250 °C, a dense and continuous conductive path is formed, ensuring strong adhesion to the substrate. Temperature-monitoring results indicate that the sensor exhibits a nearly linear resistance response (R² > 0.999) across a broad detection range of 20–200 °C. It also demonstrates high sensitivity, characterized by a temperature coefficient of resistance (TCR) of 2.15 × 10^−3/°C at 20 °C. In repeated thermal cycling tests, the sensor demonstrates excellent repeatability and stability over 100 cycles, with resistance fluctuations kept within 0.5% and negligible hysteresis observed. These findings confirm the feasibility of using AJP technology to fabricate high-performance conformal sensors on complex surfaces, offering a promising strategy for the development of intelligent structural components in next-generation aerospace engineering. Full article

P-glycoprotein (P-gp) is an ATP-driven transporter that effluxes a wide range of xenobiotics from cells, and its overexpression is a primary cause of multidrug resistance (MDR) in cancer. It is well-established that P-gp functions through conformational changes, yet its large-scale structural dynamics at work have been unexplored. Here, we directly visualized single P-gp molecules reconstituted in nanodiscs using high-speed atomic force microscopy (HS-AFM). The HS-AFM movies revealed that P-gp is intrinsically dynamic in its apo state, with its nucleotide-binding domains (NBDs) undergoing large, spontaneous opening and closing motions. However, addition of ATP stabilized a conformation characterized by NBD proximity with a strong tendency toward closure. We then leveraged this dynamic viewpoint to elucidate the relationship between Elacridar’s function and the resulting structural dynamics of P-gp. Elacridar is designed to overcome multidrug resistance (MDR) in cancer and acts as a potent dual inhibitor of both P-gp and the Breast Cancer Resistance Protein (BCRP), effectively blocking the drug efflux function of these transporters. This inhibitor has suggested concentration-dependent function: it is effluxed as a substrate at low concentrations and acts as an inhibitor at high concentrations. Our direct observations revealed that low concentrations induced active dynamics in P-gp, whereas high concentrations severely restricted its motion, leading to a rigid, non-productive state. Our study provides critical insights into how observing molecular motion itself can unravel complex biological mechanisms. Full article

Carbapenem-resistant Enterobacterales (CREs) pose a critical threat to global public health, largely driven by the enzymatic activity of Klebsiella pneumoniae carbapenemase-2 (KPC-2), a class A serine β-lactamase that hydrolyzes most β-lactam antibiotics. While β-lactamase inhibitors like avibactam offer temporary relief, emerging KPC variants demand novel, sustainable inhibitory scaffolds. This study aimed to identify and characterize potential natural inhibitors of KPC-2 from Pongamia pinnata, leveraging a comprehensive in silico workflow. A curated library of 86 phytochemicals was docked against the active site of KPC-2 (PDB ID: 3DW0). The top-performing ligands were subjected to ADMET profiling (pkCSM), and 100 ns molecular dynamics simulations (GROMACS) to evaluate structural stability and interaction persistence, using avibactam as control. Ponganone V exhibited the most favorable binding energy (−9.0 kcal/mol), engaging Ser70 via a hydrogen bond and forming π–π interactions with Trp105. Glabrachromene II demonstrated a broader interaction network but reduced long-term stability. ADMET analysis confirmed high intestinal absorption, non-mutagenicity, and absence of hERG inhibition for both ligands. Molecular dynamics simulations revealed that Ponganone V maintained compact structure and stable hydrogen bonding throughout the 100 ns trajectory, closely mirroring the behavior of avibactam, whereas Glabrachromene II displayed increased fluctuation and loss of compactness beyond 80 ns. Principal Component Analysis (PCA) further supported these findings, with Ponganone V showing restricted conformational motion and a single deep free energy basin, while avibactam and Glabrachromene II exhibited broader conformational sampling and multiple energy minima. The integrated computational findings highlight Ponganone V as a potent and pharmacologically viable natural KPC-2 inhibitor, with strong binding affinity, sustained structural stability, and minimal toxicity. This study underscores the untapped potential of Pongamia pinnata phytochemicals as future anti-resistance therapeutics and provides a rational basis for their experimental validation. Full article

Sestrin2 (SESN2) is a highly conserved stress-inducible protein that serves as a central hub for integrating cellular responses to nutrient availability, oxidative stress, and endoplasmic reticulum (ER) stress. A key function of SESN2 is its role as a direct sensor for the branched-chain amino acid (BCAA) leucine, which modulates the activity of the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cell growth and metabolism. While the functional link between leucine and SESN2 is well-established, the precise molecular determinants that confer its high specificity for leucine over other BCAAs, such as isoleucine and valine, remain poorly understood. This study employs an integrated computational approach, spanning atomic interactions to global protein dynamics, combining molecular docking, extensive all-atom molecular dynamics (MD) simulations, and binding free energy calculations, to elucidate the structural and dynamic basis of BCAA-SESN2 recognition. Our thermodynamic analysis reveals a distinct binding affinity hierarchy (Leucine > Isoleucine > Valine), which is primarily driven by superior van der Waals interactions and the shape complementarity of leucine’s isobutyl side chain within the protein’s hydrophobic pocket. Critically, a quantitative analysis of the conformational ensemble reveals that leucine induces a dramatic collapse of the protein’s structural heterogeneity. This “conformational locking” mechanism funnels the flexible, high-entropy unbound protein—which samples 35 distinct conformations—into a sharply restricted ensemble of just 9 stable states. This four-fold reduction in conformational freedom is accompanied by a kinetic trapping effect, which significantly lowers the rate of transitions between states. This process of conformational selection stabilizes a well-defined, signaling-competent structure, providing a comprehensive, atom-to-global-scale model of SESN2’s function. In the context of these findings, this work provides a critical framework for understanding SESN2’s complex role in disease and offers a clear rationale for the design of next-generation allosteric therapeutics. Full article

N-oxides are emerging as versatile tools for modulating peptide conformation due to their strong proton-accepting ability and distinct electronic properties. In this study, we report the first crystallographic evidence that an N-oxidized peptide (NOP 5) containing a proline residue forms an intramolecular six-membered hydrogen bond between the N-oxide oxygen and an adjacent amide proton. This conformational motif is not restricted to proline-containing sequences: NMR spectroscopic analyses (including DMSO-d₆ titration, VT-NMR, NOE, and concentration-dependent studies) reveal that NOPs 7 and 9, in which proline is replaced by glycine, adopt the same hydrogen-bonded ring structure in aprotic solvents. Remarkably, this conformation persists even in protic solvent (CD₃OH), indicating the robustness of the N-oxide-induced hydrogen bond. DFT calculations further support the experimental findings and rationalize the conformational preferences of NOPs 5 and 7. These results establish N-oxide as a potent and generalizable constraint for stabilizing peptide secondary structures, offering a new strategy for the design of peptidomimetics with tunable rigidity and solvent stability. Full article

In many mountainous areas of China, frequent geological disasters pose a serious threat to human life and property. The Luding “9.5” earthquake triggered a large number of landslide disasters, causing serious loss of life and property. Therefore, it is extremely urgent to carry out research on the stability analysis and treatment methods of landslides in the Luding area. In this paper, the Caiyangba landslide in Yanzigou Town, Luding County, is taken as the research object. The slope model is constructed by Midas to study the stability development law of Caiyangba landslide under different rainfall conditions and seismic conditions, and to explore the feasibility of the “anchor lattice treatment method”. The results show that the “anchor lattice treatment method” can effectively improve the stability of the slope under rainfall conditions. The improvement effect of slope stability decreases with the increase in rainfall duration and rainfall. The development law of the slope stability coefficient with rainfall duration in WMG (the working condition of not adopting the “anchor lattice treatment method” is referred to as WMG) and MG (the working condition of adopting the “anchor lattice treatment method” is referred to as MG) conditions conform to the development law of exponential function, and the expression of instantaneous change rate of slope stability coefficient is derived. The above function can also well explain the development law of X-direction displacement and Y-direction displacement of SP (school: monitoring point) and RP (road: monitoring point); the development law of the instantaneous change rate of displacement. Under the influence of ground motion, the improvement effect of the “anchor lattice treatment method” on the slope stability coefficient is limited, but the improvement effect of slope stability increases with the increase in seismic intensity. The slope stability coefficient and the displacement of SP and RP show obvious fluctuation with time, and the fluctuation law is similar to that of ground motion records. It is recommended to add a gravity-retaining wall at the foot of the slope. The teaching building reduces the number of floors and increases the number of pile foundations. Roads should restrict the passage of heavy vehicles, such as cars and strictly stacked items. The above results can provide a theoretical reference for the sustainable treatment and sustainable development of landslides in the Luding area. Full article

Background: Mullegama–Klein–Martinez syndrome (MKMS; OMIM #301022) is an X-linked cohesinopathy caused by pathogenic variants in STAG2, which encodes a subunit of the cohesin complex responsible for chromosomal segregation and transcriptional regulation. Individuals typically present with developmental delay, microcephaly, dysmorphic features, and variable congenital anomalies, though complex cardiac malformations are uncommon. Case Presentation: We report a female infant presenting on the first day of life with complex congenital heart disease, including pulmonary atresia, double-outlet right ventricle, large subaortic ventricular septal defect, and patent ductus arteriosus. She exhibited intrauterine growth restriction, mild craniofacial dysmorphism, and left upper-extremity hypotonia. Stepwise genetic evaluation revealed a de novo likely pathogenic STAG2 frameshift variant, c.2972_2975dup (p.His992Glnfs*11), identified by rapid trio whole-exome sequencing. This variant truncates the C-terminal domain critical for cohesin binding. A 3D structural model generated by SWISS-MODEL demonstrated disruption of β-strand and loop conformations within this domain, consistent with loss of cohesin complex stability. Conclusions: This case expands the phenotypic spectrum of STAG2-related MKM and highlights the role of STAG2 in cardiac development. Recognition of such presentations supports the inclusion of STAG2 in the differential diagnosis for complex congenital heart disease and underscores the diagnostic utility of rapid trio exome sequencing in neonatal care. The utility of 3D protein modeling to illustrate structural consequences of truncating variants provides valuable insight into variant pathogenicity and supports precision diagnosis in cohesinopathies. Full article

We consider detailed cosmological tests of dark energy models obtained from the general conformal transformation of the Kropina metric, representing an $(\alpha ,\beta )$-type Finslerian geometry. In particular, we restrict our analysis to the osculating Barthel–Kropina geometry. The Kropina metric function is defined as the ratio of the square of a Riemannian metric $\alpha$ and of the one-form $\beta$. In this framework, we also consider the role of the conformal transformations of the metric, which allows us to introduce a family of conformal Barthel–Kropina theories in an osculating geometry. The models obtained in this way are described by second-order field equations, in the presence of an effective scalar field induced by the conformal factor. The generalized Friedmann equations of the model are obtained by adopting for the Riemannian metric $\alpha$ the Friedmann–Lemaitre–Robertson–Walker representation. In order to close the cosmological field equations, we assume a specific relationship between the component of the one-form $\beta$ and the conformal factor. With this assumption, the cosmological evolution is determined by the initial conditions of the scalar field and a single free parameter $\gamma$ of the model. The conformal Barthel–Kropina cosmological models are compared against several observational datasets, including Cosmic Chronometers, Type Ia Supernovae, and Baryon Acoustic Oscillations, using a Markov Chain Monte Carlo (MCMC) analysis, which allows the determination of $\gamma$. A comparison with the predictions of standard $\mathsf{\Lambda }$CDM model is also performed. Our results indicate that the conformal osculating Barthel–Kropina model can be considered as a successful, and simple, alternative to standard cosmological models. Full article

Long-term water flooding development has exacerbated reservoir heterogeneity, and traditional polymer gels are unable to simultaneously meet the requirements of high injectability and strong plugging strength. If the viscosity of the polymer is high, its injectability will be poor; on the contrary the viscosity is low, the plugging strength will be poor, which severely restricts the oil recovery effect. This study synthesized an NBAP through free radical polymerization followed by a substitution reaction, and a plugging system (NBAP-B1) was subsequently formed by combining the polymer with a Cr³⁺ crosslinking agent. Rheological experiments demonstrated that the system exhibited significant shear thinning behavior, as well as excellent temperature and salt resistance. Gelation experiments indicated that the NBAP-B1 system featured controllable gelation time (20~150 h) and high gelation strength (J grade), along with excellent resistance to both high temperature and high salinity. Microscopic analysis revealed that the gel formed by NBAP-B1 possessed a dense and uniform three-dimensional network structure. Injection and plugging experiments demonstrated that NBAP-B1 exhibited optimal injectability and outstanding plugging performance. Additionally, profile control and displacement tests revealed a 18.37% enhancement in oil recovery efficiency by water flooding after the application of NBAP-B1 for conformance control. Collectively, these results demonstrate that the NBAP exhibits significantly superior performance compared to single component systems. It combines excellent injectability with high strength plugging capability, offering an effective approach for enhancing oil recovery in low permeability reservoirs. Full article

To address limitations such as cleaning difficulties or secondary contamination/damage of cultural relics caused by the uncontrollable diffusion of water/cleaning agent/dirty liquids during the cleaning process in traditional cleaning methods, this study, using cotton textiles as an example, systematically investigated the cleaning efficacy of four in situ methods (blank gel, cleaning gel, ultrasonic emulsification, and gel + ultrasonic emulsification synergistic cleaning) on eight types of stains, including sand, clay, rust, blood, ink, oil, and mixed solid/liquid stains. Building upon this, this study proposed an efficient, targeted, in situ, and controllable cleaning strategy tailored for fragile, stained textile relics. Results demonstrated that, regardless of the stain type, the synergistic cleaning method of G+U (gel poultice + ultrasonic emulsification) consistently outperformed the cleaning methods of blank gel poultice, cleaning gel poultice, and ultrasonic emulsification. Furthermore, the gel loaded with cleaning agents was always more effective than the blank gel (unloaded cleaning agents). The poultice methods of blank gel and cleaning gel were better suited for solid stains, while the ultrasonic emulsification cleaning method was more effective for liquid stains. Meanwhile, it was also found that the optimal cleaning method proposed in this study (the G+U synergistic cleaning method) was a cleaning method that restricted the cleaning agent within the gel network/emulsion system, and utilized the porous network physical structure of gel, the chemical action of emulsion’s wetting/dissolving dirt, and the cavitation synergistic effect of ultrasound to achieve the targeted removal of contaminants from relics’ surfaces. Crucially, the cleaning process of G+U also had the characteristics of controlling the cleaning area at the designated position and effectively regulating the diffusion rate of the cleaning solution within the treatment zone, as well as the reaction intensity. Therefore, the proposed optimal (the synergistic cleaning method of G+U) cleaning method conforms to the significant implementation of the “minimal intervention and maximal preservation” principle in modern cultural heritage conservation. Consequently, the synergistic cleaning method of G+U holds promise for practical application in artifact cleaning work. Full article

The SETD6 protein lysine methyltransferase monomethylates specific lysine residues in a diverse set of substrates which contain the target lysine residue in a highly variable amino acid sequence context. To investigate the mechanism underlying this multispecificity, we analyzed SETD6 substrate recognition using AlphaFold 3 docking and peptide SPOT array methylation experiments. Structural modeling of the SETD6–E2F1 complex suggested that substrate binding alone is insufficient to restrict SETD6 activity to only one lysine residue, pointing to additional sequence readout at the target site. Methylation of mutational scanning peptide SPOT arrays derived from four different SETD6 substrates (E2F1 K117, H2A.Z K7, RELA K310, and H4 K12) revealed sequence preferences of SETD6 at positions −1, +2, and +3 relative to the target lysine. Notably, glycine or large aliphatic residues were favored at −1, isoleucine/valine at +2, and lysine at +3. These preferences, however, were sequence context dependent and variably exploited among different substrates, indicating conformational variability of the enzyme–substrate interface. Mutation of SETD6 residue L260, which forms a contact with the +2 site in the available SETD6-RELA structure, further demonstrated substrate-specific differences in recognition at the +2/+3 sites. Together, these findings reveal a versatile mode of peptide recognition in which the readout of each substrate position depends on the overall substrate peptide sequence. These findings can explain the multispecificity of SETD6 and similar mechanisms may underlie substrate selection in other protein methyltransferases. Full article

Traditional pneumatic soft grippers often suffer from a limited contact area and poor shape-matching performance, restricting their effectiveness in handling objects with complex or delicate surfaces. To address this problem, this study proposed an integrated soft gripper that combines pneumatic actuators with specially designed mechanical metamaterials, aiming to optimize deformation characteristics and enhance gripping surface conformity to target objects. The key contributions are as follows: (1) A novel integrated structure is designed, incorporating pneumatic actuators and mechanical metamaterials. (2) A highly efficient design framework based on deep learning is developed, incorporating forward and inverse neural networks to enable efficient performance prediction and inverse design. (3) The novel gripper is fabricated using stereolithography (SLA) and silicone casting, with experimental validation conducted via machine vision and multi-shape object tests. FEA simulations and experiments demonstrate significant improvements in shape matching: average deviations of gripping surfaces from targets are greatly reduced after optimization. This work validates that integrating mechanical metamaterials with data-driven design enhances the gripper’s adaptability, providing a feasible solution for high-performance soft gripping systems. Full article

In this study, the insufficient ability of tartary buckwheat protein (TBP) to stabilize Pickering emulsions was addressed by preparing TBP–sodium alginate (SA) composite particles via cross-linking and systematic optimization of the preparation parameters. The results showed that at a pH of 9.0 with 1.0% (w/v) TBP and 0.2% (w/v) SA, the zeta potential of the prepared TBP–SA composite particles was significantly more negative, and the particle size was significantly larger, than those of TBP, while emulsifying activity index and emulsifying stability index increased to 53.76 m²/g and 78.78%, respectively. Scanning electron microscopy confirmed the formation of a dense network structure; differential scanning calorimetry revealed a thermal denaturation temperature of 83 °C. Fourier transform infrared spectroscopy and surface hydrophobicity results indicated that the complex was formed primarily through hydrogen bonding and hydrophobic interactions between TBP and SA, which induced conformational changes in the protein. The Pickering emulsion prepared with 5% (w/v) TBP–SA composite particles and 60% (φ) oil phase was stable during 4-month storage, at a high temperature of 75 °C, high salt conditions of 600 mM, and pH of 3.0–9.0. The stabilization mechanisms may involve: (1) strong electrostatic repulsion provided by the highly negative zeta potential; (2) steric hindrance and mechanical strength imparted by the dense interfacial network; and (3) restriction of droplet mobility due to SA-induced gelation. Full article

Dihydroorotase (DHOase) catalyzes the reversible cyclization of N-carbamoyl-L-aspartate to dihydroorotate, a key step in de novo pyrimidine biosynthesis. A flexible active site loop in DHOase undergoes conformational switching between loop-in and loop-out states, influencing substrate binding, catalysis, and inhibitor recognition. In this study, we identified 5-fluoroorotate (5-FOA) and myricetin as inhibitors of Saccharomyces cerevisiae DHOase and systematically analyzed 97 crystal structures and AlphaFold 3.0 models of DHOases from 16 species representing types I, II, and III. Our results demonstrate that loop conformation is not universally ligand-dependent and varies markedly across DHOase types, with type II enzymes showing the greatest flexibility. Notably, S. cerevisiae DHOase consistently adopted the loop-in state, even with non-substrate ligands, restricting accessibility for docking-based inhibitor screening. Docking experiments with 5-FOA and myricetin confirmed that the loop-in conformation prevented productive active-site docking. These findings highlight the importance of selecting appropriate loop conformations for structure-based drug design and underscore the need to account for loop dynamics in inhibitor screening. Full article

When a city decides to undertake a certain urban project, is it modifying just the physical environment or the social fabric that dwells within? This work investigates the relationship between the geometric configuration of urban space (geometry–city) and the topology of the networks of encounters of its inhabitants (network–city) that form through daily interactions. The research departs from the hypothesis that changes in geometry–city would not significantly alter the topology of the network–city, testing this proposition conceptually through abstract computational simulations developed specifically for this study. In this simulator, abstract maps with buildings distributed over different primary geometries are generated and have activities (use: home or work) and a population assigned. Encounters of the “inhabitants” are registered while daily commute routines, enough to achieve differentiation and stability, are run. The initial results revealed that the geometry description was not enough, and definitions regarding activity attribution were also necessary. Thus, we could not confirm nor reject the original hypothesis exactly, but it had to be complemented, including the idea of an activity–city dimension. We found that despite the geometry–city per se not determining the structure of the network–city, the spatial (geometric) distribution of activities directly impacts the resulting topology. Urban geometry influences networks–city only insofar as it conforms to activity–city, defining areas for activities or restricting routing between them. But it is the geometry of localization of the activities that has a direct impact on the topology of the network–city. This conceptual discovery can have significant implications for urban planning if corroborated in real-world situations. It could suggest that land use policies may be more effective for intervening in network-based characteristics, like social cohesion and resilience, than purely morphological interventions. Full article