Journal of The Royal Society Interface最新文献

In this study, the haemodynamic factors inside the patient-specific carotid artery with stenosis are evaluated via a predictive surrogate model. The technique of proper orthogonal decomposition (POD) is used for reducing the order of the main model and consequently, the long short-term memory is employed for the prediction of main blood flow parameters, i.e. blood velocity and pressure along the patient-specific carotid artery with stenosis. The efficiency of the proposed machine learning technique has been evaluated in patient-specific carotid arteries with/without stenosis. Besides, the reconstruction error analysis is performed for different POD mode numbers. Our results demonstrate that the value of blood velocity at different stages of the cardiac cycle has a great impact on the efficiency of the proposed method for the estimation of blood haemodynamics. The presence of stenosis inside the patient-specific carotid artery intensifies the complexity of the blood flow, and consequently, the magnitude of the errors for the prediction is increased when the stenosis exists in the patient-specific carotid artery.

Changes in the mechanical properties of the extracellular matrix (ECM) are a hallmark of disease. Due to its relevance, several in vitro models have been developed for the ECM, including cell-derived matrices (CDMs). CDMs are decellularized natural ECMs assembled by cells that closely mimic the in vivo stromal fibre organization and molecular content. Here, we applied atomic force microscopy-force spectroscopy (AFM-FS) to evaluate the nanomechanical properties of CDMs obtained from patients diagnosed with collagen VI-related congenital muscular dystrophies (COL6-RDs). COL6-RDs are a set of neuromuscular conditions caused by pathogenic variants in any of the three major COL6 genes, which result in deficiency or dysfunction of the COL6 incorporated into the ECM of connective tissues. Current diagnosis includes the genetic confirmation of the disease and categorization of the phenotype based on maximum motor ability, as no direct correlation exists between genotype and phenotype of COL6-RDs. We describe differences in the elastic modulus (E) among CDMs from patients with different clinical phenotypes, as well as the restoration of E in CDMs obtained from genetically edited cells. Results anticipate the potential of the nanomechanical analysis of CDMs as a complementary clinical tool, providing phenotypic information about COL6-RDs and their response to gene therapies.

The lateral moving resistance of a liquid droplet on a solid surface generally increases with velocity and is dominated by the non-viscous wetting line friction. Many superhydrophobic man-made and biological surfaces have minimal, nevertheless speed-sensitive, water droplet friction, limiting their potential to reduce drag at high speeds in natural situations. Using an in situ surface force apparatus, we demonstrated low and remarkably speed-insensitive (over 300-fold) water bridge sliding friction on a goose feather vane. Detailed analyses suggest a dominant, hidden energy dissipation channel probably related to the deformation and elastic recovery of feather's characteristic metamaterial-like structure, which also results in feather's speed insensitive (from 0.1 to 1 mm s^-1) ultra-low dry sliding friction coefficient observed in this study (approx. 0.07). The new insights gained have the potential to motivate novel approaches to the design of all-weather and speed-insensitive low-friction surfaces with practical applications in aviation and lubrication technology.

Natural fliers with flapping wings face the dual challenges of energy efficiency and active control of wing motion for achieving diverse modes of flight. It is hypothesized that flapping-wing systems use resonance to improve muscle mechanical output energy efficiency, a principle often followed in bioinspired flapping-wing robots. However, resonance can limit the degree of active control, a trade-off rooted in the dynamics of wing motor systems and can be potentially reflected in muscle work loops. To systematically investigate how energy efficiency trades off with active control of wingbeat frequency and amplitude, here we developed a parsimonious model of the wing motor system with either synchronous or asynchronous power muscles. We then non-dimensionalized the model and performed simulations to examine model characteristics as functions of Weis-Fogh number and dimensionless flapping frequency. For synchronous power muscles, our model predicts that energy efficiency trades off with frequency control rather than amplitude control at high Weis-Fogh numbers; however, no such trade-off was found for models with asynchronous power muscles. The work loops alone are insufficient to fully capture wing motor characteristics, and therefore fail to directly reflect the trade-offs. Finally, using simulation results, we predict that natural fliers function at Weis-Fogh numbers close to 1.

Novel therapeutic strategies are essential for enhancing efficacy and accelerating the treatment of diabetes mellitus. This investigation focused on incorporating empagliflozin into a composite of polylactic acid and polycaprolactone, resulting in the fabrication of drug-loaded fibrous patches (DFPs) for transdermal application, both by electrospinning (ES) and by pressurized gyration (PG). Scanning electron microscopy results revealed that DFPs generated through the PG method exhibited smaller diameters and a larger surface area than ES. Fourier-transform infrared spectroscopy and X-ray powder diffraction analyses confirmed the successful encapsulation of the drug in both DFPs. DFPs/PG exhibited a controlled release of 98.7 ± 1.3% of the total drug over 14 days, while DFPs/ES released 98.1 ± 2.1% in 12 days, according to in vitro drug release studies. This study underscores that the PG method can generate DFPs with extended controlled release. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide test results validate the biocompatibility of DFPs, affirming their lack of adverse effects on human dermal fibroblast cell viability. Consequently, DFPs can be manufactured for transdermal administration using PG, exhibiting similar characteristics to ES but with the added advantage of mass production capability.

Extensive efforts have been devoted to enhancing the translation efficiency of mRNA delivered to mammalian cells via codon optimization. However, the impact of codon choice on mRNA stability remains underexplored. In this study, we investigated the influence of codon usage on mRNA degradation kinetics in cultured human cell lines using live-cell imaging on single-cell arrays. By measuring mRNA lifetimes at the single-cell level for synthetic mRNA constructs, we confirmed that mRNAs containing slowly translated codon windows have shorter lifetimes. Unexpectedly, these mRNAs did not exhibit decreased stability in the presence of small interfering RNA (siRNA) compared with the unmutated sequence, suggesting an interference of different concurrent degradation mechanisms. We employed stochastic simulations to predict ribosome density along the open reading frame, revealing that the ribosome densities correlated with mRNA stability in a cell-type- and codon-position-specific manner. In summary, our results suggest that the effect of codon choice and its influence on mRNA lifetime is context-dependent with respect to cell type, codon position and RNA interference.

The Ebola virus (EV) persists in animal populations, with zoonotic transmission to humans occurring every few months or years. When zoonotic transmission arises, it is important to understand which interventions are most effective at preventing a major outbreak driven by human-to-human transmission. Here, we analyse a mathematical model of EV transmission and calculate the probability of a major outbreak starting from a single introduced case. We consider community, funeral and healthcare facility transmission and conduct sensitivity analyses to explore the effects of non-pharmaceutical interventions (NPIs) that influence these transmission routes. We find that, if the index case is treated in the community, then the elimination of transmission at funerals reduces the probability of a major outbreak substantially (from 0.410 to 0.066 under our baseline model parametrization). However, eliminating the risk of major outbreaks entirely requires combinations of measures that limit transmission in different settings, such as community engagement to promote safe burial practices and implementation of barrier nursing in healthcare facilities. In addition to generating insights into the drivers of Ebola outbreaks, this research provides a modelling framework for assessing the effectiveness of interventions at mitigating outbreaks of other infectious diseases with transmission in multiple settings.

Patterns found in structural materials of biological origin are an excellent source of inspiration for engineers. The root fibres (basalia spicules) of the marine sponge Euplectella aspergillum anchor it to the ocean floor and exhibit a lamellar architecture. It is generally thought that the spicule's architecture contributes to the spicule's fracture toughness. However, in recent experiments, the spicules' architecture did not contribute to their fracture toughness in a statistically significant way, with their fracture initiation toughness being similar to that of synthetic glass. In this article, we present a mechanics model and show that the spicule's architecture could be contributing to its strength, potentially benefiting the sponge's survival. When a spicule forms a loop, we find that its layers can increase the spicule's strength by reducing the bending stress induced by the tensile load transmitted along its length.

While biophysical studies have unravelled properties of specific proteins in vitro, characterizing globally their native state within the cell remains a challenge. In particular, protein adaptation to harsh intracellular physical and chemical conditions is poorly understood. Extremophiles, which thrive in severe environments, are good models for the study of such adaptation. Five haloarchaeal species, isolated from hypersaline environments, were used to assess correlations between intracellular salt concentrations and molecular dynamics properties. In cellulo protein stability was measured using nano differential scanning fluorimetry, and neutron spectrometry was used to determine molecular dynamics resilience and global flexibility. It was found that high intracellular accumulation of Mg²⁺ and low intracellular accumulation of K⁺ were correlated with higher stability and resilience. Sequence traits associated with mean proteome halophilicity, such as decreased hydrophobicity and increased acidity, weighted by the relative abundance of each protein, were also correlated with stability and resilience. Haloferax mediterranei, however, was found to be an exception as its proteome showed the highest in cellulo molecular stability and resilience associated with fewest sequence traits related to halophilicity, highlighting the significance of the intracellular salt environment in determining proteome biophysical properties.

Determining the mechano-structural relations in biological materials with hierarchical structure is crucial to understanding natural optimization strategies and designing functional bioinspired composites. However, measuring the nanoscale mechanics and dynamic response is challenging when the specimen geometry and loading environment are physiologically complex. To overcome this challenge, we develop a combination of synchrotron X-ray diffraction testing and analytical modelling to explore the mechano-structural changes during bending loads on stomatopod cuticle. Stomatopod cuticle is an example of a hierarchical biomaterial optimized for high impact and bending resistance. Using models for large deformations of elastic continua, we measure cuticle strains from macroscopic deformations and combine diffraction-based fibril strains with stresses to quantify the local elastic moduli and nanoscale strain concentration factors, which are found to vary across cuticle sub-regions and under different flexion loading modes. This approach has the advantage of identifying constituent biomaterial properties and mechanisms in situ and is also suitable for studying time-dependent changes, such as concurrent strains of the nanofibrous phase that occur during physiological loading.