Investigation of the optimal cutting depth in small incision lenticule extraction based on a collagen fibril crimping constitutive model of the cornea.

To investigate the optimal cutting depth (Cap) in small incision lenticule extraction from the perspective of corneal biomechanics, a three-dimensional finite element model of the cornea was established using a stromal sub-regional material model to simulate small incision lenticule extraction. The displacement difference PΔ at the central point of the posterior corneal surface before and after lenticule extraction, as well as the von Mises stress at four points of different thicknesses in the center of the cornea, were analyzed using the finite element model considering the hyperelastic property and the difference in stiffness between the anterior and posterior of the cornea. The numerical curves of PΔ-Cap and von Mises Stress-Cap relations at different diopters show that the displacement difference PΔ has a smallest value at the same diopter. In this case, the von Mises stress at four points with different thicknesses in the center of the cornea was also minimal. Which means that the optimal cutting depth exsisting in the cornea. Moreover, PΔ-Cap curves for different depth of stromal stiffness boundaries show that the optimal cap thickness would change with the depth of the stromal stiffness boundary. These results are of guiding significance for accurately formulating small incision lenticule extraction surgery plans and contribute to the advancement of research on the biomechanical properties of the cornea.

An idealized human cardiomyocyte finite element model for studying the interaction between the cross-bridge state and cell mechanical response.

The mechanical state of cardiomyocyte is directly related to the structure and function of internal sarcomeres. In the field of computational cardiac mechanics, attempts to establish models of human cardiomyocyte with a detailed representation of sarcomere cross-bridge (XB) are rare. In this study, we established a computational model for a cardiomyocyte with idealized geometry while containing a representative sarcomere composed of thick filament, thin filament, titin filament, and Z-disc. The formation of XB with passive tension in the model was simulated with the finite element (FE) method, and stochastic FE analyses were further carried out in conjunction with six sigma analysis to explore the interaction between the S1 power stroke and the twitch mechanics of cardiomyocyte. The proposed modeling method may help us better understand the working state of cardiomyocyte, and offer a potential means for exploring the cell-level mechanisms of cardiac diseases.

A 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system applied to predict postsplenectomy hemodynamic metrics.

Splenectomy is a common surgery for portal hypertensive patients with splenomegaly. Although splenectomy is able to effectively relieve the complications of portal hypertension, it also increases the risk of portal venous system thrombosis remarkably. Previous studies demonstrated that the hemodynamic metrics of the portal venous system could be employed in predicting the risk of postsplenectomy thrombosis, and 3D models were utilized to simulate the blood flow in the portal venous system. Aiming to reflect the global effect of splenectomy and better simulate the hemodynamic metrics, in this study, a 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system was constructed based on population-averaged data in combination with patient-specific preoperative clinical measurements. The pre- and postoperative global blood flows as well as the variations were calculated successfully, and the flow field and time-averaged wall shear stress of the portal venous system were simulated. The model-simulated spatial distributions of the hemodynamic metrics in the portal venous system were comparable with the regions suffering from thrombosis after splenectomy. These results imply that the present model could reflect the reallocation of the blood flow in the splanchnic circulation after splenectomy and simulate the hemodynamic metrics of the portal venous system, which would promote the more accurate risk stratification of postsplenectomy thrombosis and improve the patient-specific postoperative management.Clinical Relevance- The computational model developed by the present study provides a feasible scheme for simulating postsplenectomy hemodynamic metrics of the portal venous system more accurately, which would benefit the risk prediction and prophylaxis of portal venous system thrombosis for portal hypertensive patients receiving splenectomy.

Biaxial hyperelastic and anisotropic behaviors of the corneal anterior central stroma along the preferential fibril orientations. Part I: Measurement and calibration of personalized stress-strain curves.

Lacking specimens is the biggest limitation of studying the mechanical behaviors of human corneal. Extracting stress-strain curves is the crucial step in investigating hyperelastic and anisotropic properties of human cornea. 15 human corneal specimens extracted from the small incision lenticule extraction (SMILE) surgery were applied in this study. To accurately measure the personalized true stress-strain curve using corneal lenticules, the digital image correlation (DIC) method and finite element method were used to calibrate the stress and the strain of the biaxial extension test. The hyperelastic load-displacement curves obtained from the biaxial extension test were performed in preferential fibril orientations, which are arranged along the nasal-temporal (NT) and the superior-inferior (SI) directions within the anterior central stroma. The displacement and strain fields were accurately calibrated and calculated using the digital image correlation (DIC) method. A conversion equation was given to convert the effective engineering strain to the true strain. The stress field distribution, which was simulated using the finite element method, was verified. Based on this, the effective nominal stress with personalized characteristics was calibrated. The personalized stress-strain curves containing individual characteristic, like diopter and anterior surface curvature, was accurately measured in this study. These results provide an experimental method using biaxial tensile test with corneal lenticules. It is the foundation for investigating the hyperelasticity and anisotropy of the central anterior stroma of human cornea.

The Influence of Aortic Valve Disease on Coronary Hemodynamics: A Computational Model-Based Study.

Aortic valve disease (AVD) often coexists with coronary artery disease (CAD), but whether and how the two diseases are correlated remains poorly understood. In this study, a zero-three dimensional (0-3D) multi-scale modeling method was developed to integrate coronary artery hemodynamics, aortic valve dynamics, coronary flow autoregulation mechanism, and systemic hemodynamics into a unique model system, thereby yielding a mathematical tool for quantifying the influences of aortic valve stenosis (AS) and aortic valve regurgitation (AR) on hemodynamics in large coronary arteries. The model was applied to simulate blood flows in six patient-specific left anterior descending coronary arteries (LADs) under various aortic valve conditions (i.e., control (free of AVD), AS, and AR). Obtained results showed that the space-averaged oscillatory shear index (SA-OSI) was significantly higher under the AS condition but lower under the AR condition in comparison with the control condition. Relatively, the overall magnitude of wall shear stress was less affected by AVD. Further data analysis revealed that AS induced the increase in OSI in LADs mainly through its role in augmenting the low-frequency components of coronary flow waveform. These findings imply that AS might increase the risk or progression of CAD by deteriorating the hemodynamic environment in coronary arteries.

The effect of surface nucleation modulation on the mechanical and biocompatibility of metal-polymer biomaterials.

The deployment of hernia repair patches in laparoscopic procedures is gradually increasing. In this technology, however, understanding the new phases of titanium from the parent phase on polymer substrates is essential to control the microstructural transition and material properties. It remains a challenging area of condensed matter physics to predict the kinetic and thermodynamic properties of metals on polymer substrates from the molecular scale due to the lack of understanding of the properties of the metal-polymer interface. However, this paper revealed the mechanism of nucleation on polymer substrates and proposed for the first record a time-dependent regulatory mechanism for the polymer-titanium interface. The interconnection between polymer surface chain entanglement, nucleation and growth patterns, crystal structure and surface roughness were effectively unified. The secondary regulation of mechanical properties was accomplished simultaneously to satisfy the requirement of biocompatibility. Titaniumized polypropylene patches prepared by time-dependent magnetron sputtering technology demonstrated excellent interfacial mechanical properties and biocompatibility. In addition, modulation by low-temperature plasma metal deposition opened a new pathway for biomaterials. This paper provides a solid theoretical basis for the research of titanium nanofilms on medical polypropylene substrates and the medical industry of implantable biomaterials, which will be of great value in the future.

Biaxial hyperelastic and anisotropic behaviors of the corneal anterior central stroma along the preferential fibril orientations. Part II: Quantitative computational analysis of mechanical response of stromal components.

To study the hyperelastic and anisotropic behaviors of the central anterior stroma for patients with myopia, 40 corneal stromal specimens extracted after small incision lenticule extraction (SMILE) surgery were used in the biaxial extension test along two preferential fibril orientations. An improved collagen fibril crimping constitutive model with a specific physical meaning was proposed to analyze the hyperelasticity and anisotropy of the stroma. The effective elastic modulus of the two families of preferentially oriented collagen fibrils and the stiffness of the non-collagenous matrix along all three directions were compared according to the specific physical meaning of the parameters. Anisotropic behavior was found in the hyperelastic properties of the corneal anterior central stroma in the preferential fibril orientations. The stiffness of non-collagenous matrix is significantly larger in the optical axis direction than in the nasal-temporal (NT) and superior-inferior (SI) directions. Moreover, individual differences between males and females slightly impact on hyperelastic and anisotropic behaviors. The differences of these behaviors were significant in the comparison of the left and right eyes. These results have a guiding significance for the accurate design of surgical plans for refractive surgery according to a patient's condition and have a driving value for the further exploration of the biomechanical properties of the whole cornea.

Computational modeling of electromechanical coupling in human cardiomyocyte applied to study hypertrophic cardiomyopathy and its drug response.

BACKGROUND AND OBJECTIVE: Knowledge of electromechanical coupling in cardiomyocyte and how it is influenced by various pathophysiological factors is fundamental to understanding the pathogenesis of myocardial disease and its response to medication, which is however hard to be thoroughly addressed by clinical/experimental studies due to technical limitations. At this point, computational modeling offers an alternative approach. The main objective of the study was to develop a computational model capable of simulating the process of electromechanical coupling and quantifying the roles of various factors in play in the human left ventricular cardiomyocyte. METHODS: A new electrophysiological model was firstly built by combining several existing electrophysiological models and incorporating the mechanism of electrophysiological homeostasis, which was subsequently coupled to models representing the cross-bridge dynamics and active force generation during excitation-contraction coupling and the passive mechanical properties of cardiomyocyte to yield an integrative electromechanical model. Model parameters were calibrated or optimized based on a large amount of experimental data. The resulting model was applied to delineate the characteristics of electromechanical coupling and explore underlying determinant factors in hypertrophic cardiomyopathy (HCM) cardiomyocyte, as well as quantify their changes in response to different medications. RESULTS: Model predictions captured the major electromechanical characteristics of cardiomyocyte under both normal physiological and HCM conditions. In comparison with normal cardiomyocyte, HCM cardiomyocyte suffered from systemic changes in both electrophysiological and mechanical variables. Numerical simulations of drug response revealed that Mavacamten and Metoprolol could both reduce the active contractility and alleviate calcium overload but had marked differential influences on many other electromechanical variables, which theoretically explained why the two drugs have differential therapeutic effects. In addition, our numerical experiments demonstrated the important role of compensatory ion transport in maintaining electrophysiological homeostasis and regulating cytoplasmic volume. CONCLUSIONS: A sophisticated computational model has the advantage of providing quantitative and integrative insights for understanding the pathogenesis and drug responses of HCM or other myocardial diseases at the level of cardiomyocyte, and hence may contribute as a useful complement to clinical/experimental studies. The model may also be coupled to tissue- or organ-level models to strengthen the physiological implications of macro-scale numerical simulations.

Inverse solution of corneal material parameters based on non-contact tonometry: A comparative study of different constitutive models.

Assessing the biomechanical properties of the cornea in vivo is important for predicting the outcome of refractive surgery, and for controlling the risk of postoperative complications. In this study, we examined the impact of corneal mechanical properties (nonlinearity and anisotropy) on the inverse solution of corneal material parameters based on the non-contact tonometry ("air puff") test. Finite element models with different constitutive models (linear-elastic, isotropic hyperelastic, and fiber-dependent) were established to simulate the non-contact tonometry test. The results showed that the corneal nonlinear mechanical property and fiber distribution had significant effects on the corneal deflection profile. These findings may help in constructing an appropriate inverse solution strategy when using the inverse finite element method and in identifying individual differences in the corneal matrix shear modulus and fiber stiffness.

Biomechanical effect of ultraviolet-A-riboflavin cross-linking on simulated human corneal stroma model and its correlation with changes in corneal stromal microstructure.

In this study, we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction (SMILE) surgery. We investigated the biomechanical effect of ultraviolet-A- riboflavin cross-linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy (TEM). Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery. Experimental models (n = 34) were established by superimposing the corneal lenticule strips until their thickness reached close to 500 µm. Corneal cross-linking (CXL) was performed subsequently using standard or accelerated protocol. Elasticity and viscosity were quantified using stress-strain extensometer. TEM was used to visualize the collagen fiber diameter and interfibrillar spacing. The relative change in Young's modulus (rel. ΔE) decreased nonlinearly with increasing stromal depth both in the standard and accelerated groups. Compared to the sham controls, the rel. ΔE in standard and accelerated CXL groups increased significantly in the anterior 400 µm and 275 µm depth, respectively. Also, the relative change in stress (rel. ΔS) was significantly lower after standard and accelerated CXL compared to sham controls. Depth analysis showed similar results for the elastic effect. TEM images showed a small, non-significant increase in fibril diameter. The interfibrillar spacing decreased significantly after standard and accelerated CXL in the anterior-mid stromal region. We noted that the increase of corneal stiffness correlated with decrease in interfibrillar spacing after CXL. The stiffening effect was depth dependent. The effect of accelerated CXL was less in the deep corneal stromal regions compared to standard CXL.

Changes and quantitative characterization of hyper-viscoelastic biomechanical properties for young corneal stroma after standard corneal cross-linking treatment with different ultraviolet-A energies.

Corneal collagen cross-linking (CXL) treatment can restore vision in patients suffering from keratoconus and corneal injury, by improving the mechanical properties of the cornea. The correlation between ultraviolet-A (UVA) irradiant energies of standard CXL (SCXL) and corneal visco-hyperelastic mechanical behavior remains unknown. In this study, SCXL with four different UVA irradiant energy doses (0-5.4 J/cm2) were administered as part of quantitative treatments of corneal stromal lenticules extracted from young myopic patients via small incision lenticule extraction (SMILE) corneal refractive surgery. Double-strip samples with symmetric geometries were cut simultaneously for SCXL treatment and non-treated control. First, 40 pairs of strips were loaded to failure to assess the mechanical parameters of the material. Then, another 40 pairs were tested using a special uniaxial tensile test including quasi-static loading-unloading, instantaneous loading, and stress relaxation, to determine the visco-hyperelastic mechanical behavior. Upon combining the collagen fibril crimping constitutive model with the quasi-linear viscoelastic model, it was observed that with increasing UVA energy dose, the corneal strength and hyperelastic stiffness were significantly enhanced, while the maximum stretch and viscosity of the cornea were significantly reduced. Considering the quantitative analysis of SCXL and the rehabilitation prediction of keratoconus treatment, the results clarify the biomechanical behavior of human corneal stroma in SCXL clinical surgery. STATEMENT OF SIGNIFICANCE: This study quantitatively analyzes the improvement in the biomechanical properties of young central corneal stroma, due to SCXL treatment with different energies. Furthermore, the correlation between the hyper-viscoelastic mechanical parameters and UVA irradiant energy doses of SCXL are clarified. The contribution of this study fills the knowledge gap of the CXL on corneal biomechanics. It can not only clarify this mechanism better but also assist with guiding SCXL surgery for individualized patient corneas.

Characterization of hyperelastic mechanical properties for youth corneal anterior central stroma based on collagen fibril crimping constitutive model.

To relate the crimping morphology of collagen fibrils to macroscopic hyperelastic responses, a four-parameter collagen fibril crimping constitutive model was developed that characterizes the hyperelastic mechanical properties of ex vivo corneal anterior central stroma from youth patients. The collagen fibril crimping degrees of the corneal stroma follow a Gaussian distribution as observed by transmission electron microscopy of the lenticules extracted from human corneas by small incision lenticule extraction (SMILE) refractive surgery. The hyperelastic parameters of pairs of corneal lenticules from 60 youth myopic patients were determined by tensile stress-stretch curves combined with individual surgical geometric features. The model, whose parameters reflect the corresponding mechanical responses, effectively describes each mechanical deformation process especially the physiological corneal deformation range. The constitutive model was embedded into a UMAT subroutine of the finite element software ABAQUS to simulate the tensile behavior of the corneal stroma, and the differences between individuals was excluded in the statistical analysis. The stromal hyperelastic properties in the two fibril preferential directions were shown to be the same. Although there was no correlation with the degree of corneal myopia, the hyperelastic mechanical properties of both the matrix and collagen fibrils decreased with increasing corneal stromal depth. The results not only have significance for SMILE refractive surgery by elucidating the biomechanical properties of a stromal surgical region but are also conducive to the future biomechanical exploration of the whole human cornea.

Bimetal-organic framework derived Cu(NiCo)2S4/Ni3S4 electrode material with hierarchical hollow heterostructure for high performance energy storage.

Rational design of electrical active materials with high performance for energy storage and conversion is of great significance. Herein, Cu(NiCo)2S4/Ni3S4, a three-dimensional (3D) hierarchical hollow heterostructured electrode material, is designed by etching the well-defined bimetal organic framework (MOF) via sequential in-situ ion-exchange processes. This trimetallic sulfides with unique structure provide large surface area, hierarchical pore distribution and enhanced electrical conductivity, can enrich the active sites for redox reactions, facilitate electrolyte penetration and rapid charge transfer kinetics. As a result, the Cu(NiCo)2S4/Ni3S4 electrode exhibits a high specific capacitance of 1320 F/g at 1 A/g and excellent rate performance (only 15% of capacitance is attenuated when the current density is increased by 20 times). Furthermore, a fabricated hybrid supercapacitor of Cu(NiCo)2S4/Ni3S4/AC can deliver a maximum energy density of 40.8 Wh/kg, remarkable power density of 7859.2 W/kg and superior cycling stability (85% retention of capacitance after 5000 cycles), demonstrating great potential for practical applications in energy storage and conversion devices.

Uniform generation of NiCo2S4 with 3D honeycomb-like network structure on carbon cloth as advanced electrode materials for flexible supercapacitors.

Direct generation of active materials on carbon cloth (CC) is regarded as an efficient and convenient means to obtain flexible electrodes with high supercapacitor performance. However, uniform generation of active materials on the both sides of CC remains a great challenge. Herein, a facile hanging-hydrothermal method was used to directly generate uniform NiCo2S4 nanosheet arrays on carbon cloth (NiCo2S4/CC), which was then utilized as the positive electrode for flexible supercapacitors. Taking advantage of the unique and uniform honeycomb-like structure of NiCo2S4 nanosheets, the obtained NiCo2S4/CC electrode can deliver an excellent specific capacitance (1638 F g-1 at 1 A g-1), which is significantly higher than NiCo2O4/CC electrode (657.4 F g-1 at 1 A g-1). A two-electrode flexible supercapacitor was assembled using NiCo2S4/CC as positive electrode and carbon cloth coated with activated carbon as negative electrode and revealed a high energy density of 25.2 Wh kg-1 at a power density of 799.6 W kg-1, highlighting its great potential for flexible supercapacitor applications.

Metabolic Inhibitors of O-GlcNAc Transferase That Act In†Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.

O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT). O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes. Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice. These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells. We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues. Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.