The lack of representative in vitro models recapitulating human tendon (patho)physiology is among the major factors hindering consistent progress in the knowledge-based development of adequate therapies for tendinopathy.Here, an organotypic 3D tendon-on-chip model is designed that allows studying the spatiotemporal dynamics of its cellular and molecular mechanisms.Combining the synergistic effects of a bioactive hydrogel matrix with the biophysical cues of magnetic microfibers directly aligned on the microfluidic chip, it is possible to recreate the anisotropic architecture, cell patterns, and phenotype of tendon intrinsic (core) compartment. When incorporated with vascular-like vessels emulating the interface between its intrinsic-extrinsic compartments, crosstalk with endothelial cells are found to drive stromal tenocytes toward a reparative profile. This platform is further used to study adaptive immune cell responses at the onset of tissue inflammation, focusing on interactions between tendon compartment tenocytes and circulating T cells.The proinflammatory signature resulting from this intra/inter-cellular communication induces the recruitment of T cells into the inflamed core compartment and confirms the involvement of this cellular crosstalk in positive feedback loops leading to the amplification of tendon inflammation.Overall, the developed 3D tendon-on-chip provides a powerful new tool enabling mechanistic studies on the pathogenesis of tendinopathy as well as for assessing new therapies.

BACKGROUND: Construction of meat analogs based on pea protein isolate (PPI) alone by high moisture extrusion (HME) is diffocult as a result of the lack of anisotropic structures. In the present study, 0%-15% of whey protein (WP) was introduced to PPI to make hybrid blends, which were used to construct HME extrudates.
RESULTS: WP enhanced the hardness, adhesive, cohesiveness and gumminess of the extrudates and facilitated the formation of a distinct anisotropic structure of PPI. The fibrous degrees of the extrudates containing 10% and 15% WP were around 1.50. The addition of WP, which has more -SH groups, increased the disulfide bonds and hydrogen bonding in the extrudates, leading to a denser cross-linked structure. Particle size distribution and Fourier transform infrared analysis showed that WP induced more compact structured aggregates and more β-sheet structures in the extrudates. Furthermore, the higher hydration capacity of WP may also help form a dilute melt and generate a more pronounced plug flow, assisting the formation of fiber structures of PPI.
CONCLUSIONS: The present study demonstrates that WP is a potential modifier, which could be used to improve the structure of PPI-based meat analogs. © 2024 Society of Chemical Industry.

The mechanical properties of the sclera play a critical role in supporting the ocular structure and maintaining its shape. However, non-invasive measurements to quantify scleral biomechanics remain challenging. Recently introduced multi-directional optical coherence elastography (OCE) combined with an air-coupled ultrasound transducer for excitation of elastic surface waves was used to estimate phase speed and shear modulus in ex vivo rabbit globes (n = 7). The scleral phase speed (12.1 ± 3.2 m/s) was directional-dependent and higher than for corneal tissue (5.9 ± 1.4 m/s). In the tested locations, the sclera proved to be more anisotropic than the cornea by a factor of 11 in the maximum of modified planar anisotropy coefficient. The scleral shear moduli, estimated using a modified Rayleigh-Lamb wave model, showed significantly higher values in the circumferential direction (65.4 ± 31.9 kPa) than in meridional (22.5 ± 7.2 kPa); and in the anterior zone (27.3 ± 9.3 kPa) than in the posterior zone (17.8 ± 7.4 kPa). The multi-directional scanning approach allowed both quantification and radial mapping of estimated parameters within a single measurement. The results indicate that multi-directional OCE provides a valuable non-invasive assessment of scleral tissue properties that may be useful in the development of improved ocular models, the evaluation of potential myopia treatment strategies, and disease characterization and monitoring.

The lung comprises multiple components including the parenchyma, airways, and visceral pleura, where each constituent displays specific material properties that together govern the whole organ\'s properties. The structural and mechanical complexity of the lung has historically undermined its comprehensive characterization, especially compared to other biological organs, such as the heart or bones. This knowledge void is particularly remarkable when considering that pulmonary disease is one of the leading causes of morbidity and mortality across the globe. Establishing the mechanical properties of the lung is central to formulating a baseline understanding of its operation, which can facilitate investigations of diseased states and how the lung will potentially respond to clinical interventions. Here, we present established and widely accepted experimental protocols for pulmonary material quantification, specifying how to extract, prepare, and test each type of lung constituent under planar biaxial tensile loading to investigate the mechanical properties, such as physiological stress-strain profiles, anisotropy, and viscoelasticity. These methods are presented across an array of commonly studied species (murine, rat, and porcine). Additionally, we highlight how such material properties may inform the construction of an inverse finite element model, which is central to implementing predictive computational tools for accurate disease diagnostics and optimized medical treatments. These presented methodologies are aimed at supporting research advancements in the field of pulmonary biomechanics and to help inaugurate future novel studies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: General procedures in lung biaxial testing Alternate Protocol 1: Parenchymal-specific preparation and loading procedures Alternate Protocol 2: Airway-specific preparation and loading procedures Alternate Protocol 3: Visceral pleura-specific preparation and loading procedures Basic Protocol 2: Computational analysis.

The \"gold standard\" for the assessment of trabecular bone structure is high-resolution micro-CT. In this technical note, we test the influence of initial scan resolution and post hoc downsampling on the quantitative and qualitative analysis of trabecular bone in a Gorilla tibia. We analyzed trabecular morphology in the right distal tibia of one Gorilla gorilla individual to investigate the impact of variation in voxel size on measured trabecular variables. For each version of the micro-CT volume, trabecular bone was segmented using the medical image analysis method. Holistic morphometric analysis was then used to analyze bone volume (BV/TV), anisotropy (DA), trabecular thickness (Tb.Th), spacing (Tb.Sp), and number (Tb.N). Increasing voxel size during initial scanning was found to have a strong impact on DA and Tb.Th measures, while BV/TV, Tb.Sp, and Tb.N were found to be less sensitive to variations in initial scan resolution. All tested parameters were not substantially influenced by downsampling up to 90 μm resolution. Color maps of BV/TV and DA also retained their distribution up to 90 μm. This study is the first to examine the effect of variation in micro-CT voxel size on the analysis of trabecular bone structure using whole epiphysis approaches. Our results indicate that microstructural variables may be measured for most trabecular parameters up to a voxel size of 90 μm for both scan and downsampled resolutions. Moreover, if only BV/TV, Tb.Sp or Tb.N is measured, even larger voxel sizes might be used without substantially affecting the results.

We develop a multiscale coarse-grain model of the NIST Monoclonal Antibody Reference Material 8671 (NISTmAb) to enable systematic computational investigations of high-concentration physical instabilities such as phase separation, clustering, and aggregation. Our multiscale coarse-graining strategy captures atomic-resolution interactions with a computational approach that is orders of magnitude more efficient than atomistic models, assuming the biomolecule can be decomposed into one or more rigid bodies with known, fixed structures. This method reduces interactions between tens of thousands of atoms to a single anisotropic interaction site. The anisotropic interaction between unique pairs of rigid bodies is precomputed over a discrete set of relative orientations and stored, allowing interactions between arbitrarily oriented rigid bodies to be interpolated from the precomputed table during coarse-grained Monte Carlo simulations. We present this approach for lysozyme and lactoferrin as a single rigid body and for the NISTmAb as three rigid bodies bound by a flexible hinge with an implicit solvent model. This coarse-graining strategy predicts experimentally measured radius of gyration and second osmotic virial coefficient data, enabling routine Monte Carlo simulation of medically relevant concentrations of interacting proteins while retaining atomistic detail. All methodologies used in this work are available in the open-source software Free Energy and Advanced Sampling Simulation Toolkit.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Understanding and characterizing the intrinsic properties of charge carrier transport across the interfaces in van der Waals heterostructures is critical to their applications in modern electronics, thermoelectrics, and optoelectronics. However, there are very few published cross-plane resistivity measurements of thin samples because these inherently 2-probe measurements must be corrected for contact and lead resistances. Here, we present a method to extract contact resistances and metal lead resistances by fitting the width dependence of the contact end voltages of top and bottom electrodes of different contact widths to a model based on current crowding. These contributions are then subtracted from the total 2-probe cross-plane resistance to obtain the cross-plane resistance of the material itself without needing multiple devices and/or etching steps. This approach was used to measure cross-plane resistivities of a (PbSe)1(VSe2)1 heterostructure containing alternating layers of PbSe and VSe2 with random in-plane rotational disorder. Several samples measured exhibited a 4 order of magnitude difference between cross-plane and in-plane resistivities over the 6-300 K temperature range. We also reported the observation of charge density wave transition in the cross-plane transport of the (PbSe)1(VSe2)1 heterostructure. The device fabrication process is fully liftoff compatible, and the method developed enables the straightforward measurement of the resistivity anisotropy of most thin film materials with nm thicknesses.

Optical anisotropy is a fundamental attribute of some crystalline materials and is quantified via birefringence. A birefringent crystal gives rise to not only asymmetrical light propagation but also attenuation along two distinct polarizations, a phenomenon called linear dichroism (LD). Two-dimensional (2D) layered materials with high in-plane and out-of-plane anisotropy have garnered interest in this regard. Mithrene, a 2D metal-organic chalcogenate (MOCHA) compound, exhibits strong excitonic resonances due to its naturally occurring multiquantum well (MQW) structure and in-plane anisotropic response in the blue wavelength (∼400-500 nm) regime. The MQW structure and the large refractive indices of mithrene allow the hybridization of the excitons with photons to form self-hybridized exciton-polaritons in mithrene crystals with appropriate thicknesses. Here, we report the giant birefringence (∼1.01) and the tunable in-plane anisotropic response of mithrene, which stem from its low symmetry crystal structure and strong excitonic properties. We show that the LD in mithrene can be tuned by leveraging the anisotropic exciton-polariton formation via the cavity coupling effect, exhibiting giant in-plane LD (∼77.1%) at room temperature. Our results indicate that mithrene is a polaritonic birefringent material for polarization-sensitive nanophotonic applications in the short wavelength regime.

At present, no consensus has been reached on the generation mechanism of anisotropy in materials fabricated by laser powder bed fusion (LPBF), and most attention has been focused on crystallographic texture. In this paper, an analysis and test were carried out on the hardness, defect distribution, residual stress distribution, and microstructure of WE43 magnesium alloy fabricated by LPBF. The results indicate that LPBF WE43 exhibits obvious anisotropy-the hardness HV of X-Z surface (129.9 HV on average) and that of Y-Z surface (130.7 HV on average) are about 33.5% higher than that of X-Y surface (97.6 HV on average), and the endurable load is smaller in the stacking direction Z compared to the X and Y directions. The factors contributing more to the anisotropy are listed as follows in sequence. Firstly, the defect area of the X-Y projection surface is about 13.2% larger than that of the other two surfaces, so this surface shows greatly reduced mechanical properties due to the exponential relationship between the material strength and the number of defects. Secondly, for laser scanning in each layer/time, the residual stress accumulation in the Z direction is higher than that in the X and Y directions, which may directly reduce the mechanical properties of the material. Finally, more fine grains are distributed in X-Z and Y-Z surfaces when comparing them with those in an X-Y surface, and this fine-grain strengthening mechanism also contributes to the anisotropy. After T5 aging heat treatment (250 °C/16 h), a stronger crystallographic texture is formed in the <0001> direction, with the orientation density index increasing from 10.92 to 21.38, and the anisotropy disappearing. This is mainly caused by the enhancement effect of the texture in the <0001> direction on the mechanical properties in the Z direction cancelling out the weakening effect of the defects in the X-Y surface in the Z direction.