Laminar Shear Research Articles

Novel insights into the correlation composition-structure-property of recyclable carbon fiber reinforced thermosetting resin composites

As widely used lightweight and high-strength materials, the sustainable development of thermosetting composites is hampered by their limited recyclability. Developing simple methods for the efficient and upgraded recycling is desirable but challenging. Herein, carbon fiber reinforced degradable thermosetting resin composites were prepared, and the effects of resin degradation process and its derivatives on the sustainable recycling of carbon fiber were studied. Through the tunable departure and re-adsorption of degradation derivatives in cleaning post-treatment, recycled carbon fibers achieved not only non-destructive recovery but also simultaneously improvements in tensile strength from 3.0 GPa to 3.7 GPa and surface energy from 47.2 mN/m to 66.7 mN/m. The adhered derivatives, rich in -NH- and oxygen-containing groups, exhibited good interactions with the fiber surface and epoxy resin. Benefiting from this, the inter laminar shear strength of recycled carbon fibers reinforced epoxy composite effectively improved 24.3 %. In this work, directly reusing resin degradation products for the recycling of reinforced fibers was proposed and the key role of the composition and distribution of degradation products in recycling properties was revealed. The strategy of integrating characteristics of components to enhance material recyclability is expected to have widespread applicability, promoting the sustainable transition for thermosetting composites.

NADPH Oxidase 4: Crucial for Endothelial Function under Hypoxia-Complementing Prostacyclin.

Aim: The primary endothelial NADPH oxidase isoform 4 (NOX4) is notably induced during hypoxia, with emerging evidence suggesting its vasoprotective role through H2O2 production. Therefore, we aimed to elucidate NOX4's significance in endothelial function under hypoxia. Methods: Human vessels, in addition to murine vessels from Nox4-/- mice, were explored. On a functional level, Mulvany myograph experiments were performed. To obtain mechanistical insights, human endothelial cells were cultured under hypoxia with inhibitors of hypoxia-inducible factors. Additionally, endothelial cells were cultured under combined hypoxia and laminar shear stress conditions. Results: In human occluded vessels, NOX4 expression strongly correlated with prostaglandin I2 synthase (PTGIS). Hypoxia significantly elevated NOX4 and PTGIS expression and activity in human endothelial cells. Inhibition of prolyl hydroxylase domain (PHD) enzymes, which stabilize hypoxia-inducible factors (HIFs), increased NOX4 and PTGIS expression even under normoxic conditions. NOX4 mRNA expression was reduced by HIF1a inhibition, while PTGIS mRNA expression was only affected by the inhibition of HIF2a under hypoxia. Endothelial function assessments revealed hypoxia-induced endothelial dysfunction in mesenteric arteries from wild-type mice. Mesenteric arteries from Nox4-/- mice exhibited an altered endothelial function under hypoxia, most prominent in the presence of cyclooxygenase inhibitor diclofenac to exclude the impact of prostacyclin. Restored protective laminar shear stress, as it might occur after thrombolysis, angioplasty, or stenting, attenuated the hypoxic response in endothelial cells, reducing HIF1a expression and its target NOX4 while enhancing eNOS expression. Conclusions: Hypoxia strongly induces NOX4 and PTGIS, with a close correlation between both factors in occluded, hypoxic human vessels. This relationship ensured endothelium-dependent vasodilation under hypoxic conditions. Protective laminar blood flow restores eNOS expression and mitigates the hypoxic response on NOX4 and PTGIS.

Engineering extracellular vesicles derived from endothelial cells sheared by laminar flow for anti-atherosclerotic therapy through reprogramming macrophage

Extracellular vesicles (EVs) secreted by endothelial cells in response to blood laminar flow play a crucial role in maintaining vascular homeostasis. However, the potential of these EVs to modulate the immune microenvironment within plaques for treating atherosclerosis remains unclear. Here, we present compelling evidence that EVs secreted by endothelial cells sheared by atheroprotective laminar shear stress (LSS-EVs) exhibit excellent immunoregulatory effects against atherosclerosis. LSS-EVs demonstrated a robust capacity to induce the conversion of M1-type macrophages into M2-type macrophages. Mechanistic investigations confirmed that LSS-EVs were enriched in miR-34c-5p and reprogrammed macrophages by targeting the TGF-β-SMAD3 signaling pathway. Moreover, we employed click chemistry to modify hyaluronic acid (HA) on the surface of LSS-EVs, enabling specific binding to the CD44 receptor expressed by inflammatory macrophages within plaques. These HA-modified LSS-EVs (HA@LSS-EVs) exhibited exceptional abilities for targeting atherosclerosis and demonstrated promising therapeutic effects both in vitro and in vivo.

Endothelial cell elongation and alignment in response to shear stress requires acetylation of microtubules.

The innermost layer of the vessel wall is constantly subjected to recurring and relenting mechanical forces by virtue of their direct contact with blood flow. Endothelial cells of the vessel are exposed to distension, pressure, and shear stress; adaptation to these hemodynamic forces requires significant remodeling of the cytoskeleton which includes changes in actin, intermediate filaments, and microtubules. While much is known about the effect of shear stress on the endothelial actin cytoskeleton; the impact of hemodynamic forces on the microtubule network has not been investigated in depth. Here we used imaging techniques and protein expression analysis to characterize how pharmacological and genetic perturbations of microtubule properties alter endothelial responses to laminar shear stress. Our findings revealed that pharmacological suppression of microtubule dynamics blocked two typical responses to laminar shear stress: endothelial elongation and alignment. The findings demonstrate the essential contribution of the microtubule network to changes in cell shape driven by mechanical forces. Furthermore, we observed a flow-dependent increase in microtubule acetylation that occurred early in the process of cell elongation. Pharmacological manipulation of microtubule acetylation showed a direct and causal relationship between acetylation and endothelial elongation. Finally, genetic inactivation of aTAT1, a microtubule acetylase, led to significant loss of acetylation as well as inhibition of cell elongation in response to flow. In contrast, loss of HDAC6, a microtubule deacetylase, resulted in robust microtubule acetylation with cells displaying faster kinetics of elongation and alignment. Taken together, our findings uncovered the critical contributions of HDAC6 and aTAT1, that through their roles in the regulation of microtubule acetylation, are key mediators of endothelial mechanotransduction.

Tracer-based metabolomics for profiling nitric oxide metabolites in a 3D microvessels-on-chip model.

Endothelial dysfunction, prevalent in cardiovascular diseases (CVDs) and linked to conditions like diabetes, hypertension, obesity, renal failure, or hypercholesterolemia, is characterized by diminished nitric oxide (NO) bioavailability-a key signaling molecule for vascular homeostasis. Current two-dimensional (2D) invitro studies on NO synthesis by endothelial cells (ECs) lack the crucial laminar shear stress, a vital factor in modulating the NO-generating enzyme, endothelial nitric oxide synthase (eNOS), under physiological conditions. Here we developed a tracer-based metabolomics approach to measure NO-specific metabolites with mass spectrometry (MS) and show the impact of fluid flow on metabolic parameters associated with NO synthesis using 2D and 3D platforms. Specifically, we tracked the conversion of stable-isotope labeled NO substrate L-Arginine to L-Citrulline and L-Ornithine to determine eNOS activity. We demonstrated clear responses in human coronary artery endothelial cells (HCAECs) cultured with 13C6, 15N4-L-Arginine, and treated with eNOS stimulator, eNOS inhibitor, and arginase inhibitor. Analysis of downstream metabolites, 13C6, 15N3 L-Citrulline and 13C5, 15N2 L-Ornithine, revealed distinct outcomes. Additionally, we evaluated the NO metabolic status in static 2D culture and 3D microvessel models with bidirectional and unidirectional fluid flow. Our 3D model exhibited significant effects, particularly in microvessels exposed to the eNOS stimulator, as indicated by the 13C6, 15N3 L-Citrulline/13C5, 15N2 L-Ornithine ratio, compared to the 2D culture. The obtained results indicate that the 2D static culture mimics an endothelial dysfunction status, while the 3D model with a unidirectional fluid flow provides a more representative physiological environment that provides a better model to study endothelial dysfunction.

Stable laminar shear stress induces G1 cell cycle arrest and autophagy in urothelial carcinoma by a torque sensor-coupled cone-and-plate device

The microenvironments of urinary systems play crucial roles in the development and metastasis of cancers due to their generation of complex temporal and spatial fluidic profiles. Because of their versatility in creating desired biomimetic flow, cone-and-plate bioreactors offer great potential for bladder cancer research. In this study, we construct a biocompatible cone-and-plate device coupled with a torque sensor, enabling the application and real-time monitoring of stable shear stress up to 50 dyne/cm². Under a stable shear stress stimulation at 12 dyne/cm2, bladder cancer cell BFTC-905 is arrested at the G1 phase with decreased cell proliferation after 24-hour treatment. This effect is associated with increased cyclin-dependent kinase inhibitors p21 and p27, inhibiting cyclin D1/CDK4 complex with dephosphorylation of serine 608 on the retinoblastoma protein. Consequently, an increase in cyclin D3 and decreases in cyclin A2 and cyclin E2 are observed. Moreover, we demonstrate that the shear stress stimulation upregulates the expression of autophagy-related proteins Beclin-1, LC3B-I and LC3B-II, while caspase cleavages are not activated under the same condition. The design of this system and its application shed new light on flow-induced phenomena in the study of urothelial carcinomas.

Microfluidic bubble-templating 3D printing of ordered macroporous hydrogels

Macroporous hydrogels have broad applications in tissue engineering, drug delivery and flexible biosensors, etc. However, it is still difficult to simultaneously control both the shape and the internal macroporosity. Here, we introduce a microfluidic bubble-templating 3D printing method based on thermosensitive composite hydrogel inks consisting of alginate and Pluronic F127. Two-phase laminar shear in coaxial microfluidics generates exceptionally monodispersed microbubbles as templates, while 3D printing technique provides spatial distribution of these microbubbles. Microbubble generation and 3D printing are coordinated and rheology of the inks are optimized to improve the systematic printability. Macroporous hydrogels with both monodispersed and gradient macropore structures are prepared and characterized. The internal anisotropic macroporosity distribution leads to inhomogeneous mechanical property in the products, making them competent as ergonomic artificial knuckle skins. The microfluidic-assisted 3D printing methodology provides a new insight for bottom-up design of porous soft materials.

Effect of Reynolds Number and Aeroelastic Scaling Upon Launch-Vehicle Ground-Wind Loads

NASA conducted a launch vehicle ground-wind-loads investigation at the NASA Langley Transonic Dynamics Tunnel to investigate wind-induced oscillations (WIOs) of a launch vehicle when exposed to ground winds before launch. Previous publications from this effort have documented the effects of an atmospheric-boundary-layer profile on WIO response and the correlation process between model-scale and full-scale wind characteristics and resulting structural loads. This paper will focus on the importance of aeroelastic scaling and the impact of Reynolds number on WIO response. As described in the literature and confirmed in the present investigation, aeroelastic effects can significantly increase the magnitude of measured loads. Additionally, vortex shedding is sensitive to nuances of the flow in the shear layer, which is governed by Reynolds number. Many wind-tunnel facilities are not capable of producing flight Reynolds numbers for the ground-wind-loads problem. At very low Reynolds numbers, laminar shear layers exhibit different behavior, resulting in different vortex frequencies, oscillating lift magnitudes, and motion sensitivities. This investigation demonstrated that low Reynolds number testing can yield substantially lower dynamic loads with less aeroelastic coupling than those acquired at flight-representative Reynolds numbers for a resonant WIO event. Additionally, a resonant response phenomenon present at flight Reynolds number was absent at low Reynolds number. Conversely, for nonresonant WIO response conditions, similar dynamic load coefficients were obtained for similar test velocities at either Reynolds number condition. These findings impact many large launch vehicles, including the NASA Space Launch System series of vehicles.

Modeling blood vessel dynamics: Effects of glucose variations on HUVECs in a hollow fiber bioreactor under laminar shear stress

This study aimed to establish a blood vessel model within a hollow fiber bioreactor to evaluate the impact of high and fluctuating glucose levels on human umbilical vein endothelial cells (HUVECs) under laminar shear stress (LSS). HUVECs were cultured for 48 h in normal (5 mM), high (20 mM), and variable (20 mM / 5 mM alternating every 24 h) glucose concentrations under LSS of 0.66 Pa. An automated medium replacement system was developed. The control cultures remained static. The analysis included cell viability via cytometric analysis, glucose consumption, lactate production via electroenzymatic methods, and the expression of 21 genes via qPCR. The percentage of apoptotic cells did not significantly differ across glucose concentrations under LSS. HUVECs favor glycolysis for energy regardless of LSS. Under LSS, the IL1B, CCL2, and SELE genes were upregulated under high-glucose conditions and downregulated under variable-glucose conditions. A few other genes related to inflammation, oxidative stress, cell adhesion and apoptosis were upregulated under high-glucose conditions. In conclusion, using the blood vessel model we effectively examined the impact of glucose profiles on HUVECs under LSS in a device replicating the cylindrical geometry of blood vessels. LSS and tubular cell arrangement might mitigate the adverse effects of variable glucose on endothelial cells.

Molecular recognition on the surface of concentrated hydrochloric acid: Hydration configuration-driven preferential recognition of Rh (III) anions with inner-coordinated water molecules

Comprehension of selective recognition of anions is confined to a phenomenological list of solvents, hardly surpassing Pedersen’s empirical observations of cationic-crown ether binding. In this work, a novel strategy employing thin-layer oil membrane extraction (TOMX) on the surface of concentrated hydrochloric acid is proposed for controllable recognition and separation of anions with different hydration configurations. Four typical chloric-complexing anions, RhCl63−, PdCl42−, PtCl62− and FeCl4−, usually coexisting in the concentrated hydrochloric acid leaching solutions of precious metal concentrates were focused. A surprising phenomenon was noticed that the octahedral RhCl5(H2O)2− anions with inner-coordinated water molecules were preferentially recognized by 18C6 macrocyclic molecule. However, the planar quadrilateral Pd (II) chloric-complexing anions with a hydration configuration via water molecules attacking the central Pd (II) atoms along the Z-axis direction can be separated subsequently. The Pt (IV) and Fe (III) chloric-complexing anions respectively with an octahedral and tetrahedral outer-coordinated hydration shell configuration were the last to be recognized. Such an order in extracting Rh (III) > Pd (II) > Pt (IV) > Fe (III) anions depends on their hydration capacity and the preferential affinity towards the interface, which is almost impossible during the conventional stirring and oil droplet dispersed extraction. Because of a lower concentration of dissociated hydrogen ions on the surface of concentrated hydrochloric acid compared to its bulk concentrations, the hydration of those chloric-complexing anions was enhanced. The Rh (III) anions with inner-coordinated water molecules exhibit a higher interfacial affinity than other anions. The water molecules entering the inner coordination layer of Rh (III) chloric-complexing anions, cooperating with its outer-coordinated hydration shell, act as a hydrogen bond “water bridge” to interact with 18C6 molecules, which makes it easier to feel the influence from the aqueous laminar shear flow under the thin-layer oil membrane, thereby driving the preferential recognition of easily hydrated Rh (III) anions at the interface. The controllable “water bridge” interactions driven by shear flow can be activated or deactivated on the surface of concentrated hydrochloric acid by adjusting the shear flow rate. This work lays a foundation for the future development of a controllable flexible molecular recognition technology at liquid–liquid interfaces.

Shaking table test on the seismic performance of prefabricated utility tunnel passing through hard-soft strata under longitudinal excitation

The earthquakes have adverse effects on utility tunnels passing through hard-soft strata. This paper is the first to conduct shaking table test on the seismic performance of prefabricated utility tunnel passing through hard-soft strata under longitudinal excitation. The standard segments of utility tunnel were made by microconcrete. The prefabricated utility tunnel was assembled by standard segments of utility tunnel through bolts. The silty clay and fine sand were selected to simulate the prototype soft and hard soils. The tests were conducted using the laminar shear box. The test cases were numerically simulated, and numerical results matched experimental results well. By analyzing the seismic responses of the acceleration distribution of the soil, the utility tunnel strain, and the opening of joint, the law and mechanism of seismic response of prefabricated utility tunnel passing through hard-soft strata were revealed. The research results indicated that the relative compressive deformation between soft and hard soils fundamentally caused the axial compressive strains at the utility tunnel segments near hard-soft soils interface. The closer the segment was to hard-soft soils interface, the larger the axial compressive strain of segment. The relative tensile deformation between soft and hard soils fundamentally caused the openings of joints near hard-soft soils interface. The closer the joint was to hard-soft soils interface, the larger the opening of joint. The different mechanical characteristics of prefabricated utility tunnel joints under tension and compression were the reason for the significant difference in seismic responses between prefabricated and integral cast-in-place utility tunnels.

Exercise-Induced Laminar Blood Flow Maintains Vascular Function by Enhanced Endothelial Homeostasis

PURPOSE: Laminar blood flow is known to play a critical role in maintaining endothelial homeostasis in blood vessels. It exerts a shear stress on the endothelial cells (ECs), which is essential for the regulation of various vascular functions. In this study, the effects of laminar blood flow-induced enhanced endothelial homeostasis on the maintenance of vascular function were investigated.METHODS: Human umbilical vein endothelial cells (HUVECs) were employed to study gene expression associated with vessel dilation and angiogenesis in response to varying shear stress levels. To assess angiogenesis, experimental mice participated in voluntary wheel running for 16 weeks. To evaluate the vascular autophagic function, the six weeks old C57BL/6 mice underwent an hour of forced treadmill running for 10 weeks. The resulting gene expression was evaluated through western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS: Disturbed flow resulting from partial ligation surgery in the mice’s carotid artery led to a decrease in angiogenic capacity compared to the laminar flow observed in ex vivo sprouting assays. Cultured HUVECs exhibited a significant increase in VEGF expression when exposed to increased durations of 20 dyne/cm² laminar shear stress (LSS). Following a 10-week treadmill exercise regimen, ECs in the carotid arteries of mice showed a significant increase in the expression of autophagic genes, such as LC3II, Atg3, and Atg7, which was not observed in smooth muscle cells (SMCs). LSS was found to boost the expression of both total and phosphorylated eNOS, genes involved in vascular dilation regulation, specifically in ECs.CONCLUSIONS: These findings suggest that laminar blood flow sustains vascular function, such as angiogenic capacity, through the enhancement of endothelial homeostasis.

MATHEMATICAL MODELLING ELECTRICALLY DRIVEN FREE SHEAR FLOWS IN A DUCT UNDER UNIFORM MAGNETIC FIELD

We consider a mathematical model of two-dimensional electrically driven laminar free shear flows in a straight duct under action of an applied uniform homogeneous magnetic field. The mathematical approach is based on studies by J.C.R. Hunt and W.E. Williams [10], Yu. Kolesnikov and H. Kalis [22,23]. We solve the system of stationary partial differential equations (PDEs) with two unknown functions of velocity U and induced magnetic field H. The flows are generated as a result of the interaction of injected electric current in liquid and the applied field using one or two couples of linear electrodes located on duct walls: three cases are considered. In dependence on direction of current injection and uniform magnetic field, the flows between the end walls are realized. Distributions of velocities and induced magnetic fields, electric current density in dependence on the Hartmann number Ha are studied. The solution of this problem is obtained analytically and numerically, using the Fourier series method and Matlab.

Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation.

Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, and this supports an anti-inflammatory phenotype. High laminar shear stress also induces flow-aligned cell elongation and front-rear polarity, but whether these are required for the anti-inflammatory phenotype is unclear. Here, we showed that Caveolin-1-rich microdomains polarize to the downstream end of ECs that are exposed to continuous high laminar flow. These microdomains were characterized by high membrane rigidity, filamentous actin (F-actin), and raft-associated lipids. Transient receptor potential vanilloid-type 4 (TRPV4) ion channels were ubiquitously expressed on the plasma membrane but mediated localized Ca2+ entry only at these microdomains where they physically interacted with clustered Caveolin-1. These focal Ca2+ bursts activated endothelial nitric oxide synthase (eNOS) within the confines of these domains. Importantly, we found that signaling at these domains required both cell body elongation and sustained flow. Finally, TRPV4 signaling at these domains was necessary and sufficient to suppress inflammatory gene expression, and exogenous activation of TRPV4 channels ameliorated the inflammatory response to stimuli both in vitro and in vivo. Our work revealed a polarized mechanosensitive signaling hub in arterial ECs that dampens inflammatory gene expression and promotes cell resilience.

DeHNSSo: The Delft Harmonic Navier-Stokes Solver for nonlinear stability problems with complex geometric features

A nonlinear Harmonic Navier-Stokes (HNS) framework is introduced for simulating instabilities in laminar spanwise-invariant shear layers, featuring sharp and smooth wall surface protuberances. While such cases play a critical role in the process of laminar-to-turbulent transition, classical stability theory analyses such as parabolized or local stability methods fail to provide (accurate) results, due to their underlying assumptions. The generalized incompressible Navier-Stokes (NS) equations are expanded in perturbed form, using a spanwise and temporal Fourier ansatz for flow perturbations. The resulting equations are discretized using spectral collocation in the wall-normal direction and finite-difference methods in the streamwise direction. The equations are then solved using a direct sparse-matrix solver. The nonlinear mode interaction terms are converged iteratively. The solution implementation makes use of a generalized domain transformation to account for geometrical smooth surface features, such as humps. No-slip conditions can be embedded in the interior domain to account for the presence of sharp surface features such as forward- or backward-facing steps. Common difficulties with Navier-Stokes solvers, such as the treatment of the outflow boundary and convergence of nonlinear terms, are considered in detail. The performance of the developed solver is evaluated against several cases of representative boundary layer instability growth, including linear and nonlinear growth of Tollmien-Schlichting waves in a Blasius boundary layer and stationary crossflow instabilities in a swept flat-plate boundary layer. The latter problem is also treated in the presence of a geometrical smooth hump and a sharp forward-facing step at the wall. HNS simulation results, such as perturbation amplitudes, growth rates, and shape functions, are compared to benchmark flow stability analysis methods such as Parabolized Stability Equations (PSE), Adaptive Harmonic Linearized Navier-Stokes (AHLNS), or Direct Numerical Simulations (DNS). Good agreement is observed in all cases. The HNS solver is subjected to a grid convergence study and a simple performance benchmark, namely memory usage and computational cost. The computational cost is found to be considerably lower than high-fidelity DNS at comparable grid resolutions. Program summaryProgram Title: DeHNSSoCPC Library link to program files:https://doi.org/10.17632/9bnms99kk2.1Developer's repository link:https://github.com/SvenWesterbeek/DeHNSSoLicensing provisions: GPLv3Programming language: MatlabSupplementary material: The supplementary material contains the code as well as a user manual.Nature of problem: Fluid flows are subject to laminar-to-turbulent transition following the growth of instabilities. To avoid computationally demanding Direct Numerical Simulations (DNS), perturbation theory is often applied to their analysis. However, classical stability methods based on the Orr-Sommerfeld equation or the Parabolized Stability Equations neglect the influence of streamwise gradients in varying degrees. The validity of these assumptions is difficult to estimate a priori.Solution method: The Delft Harmonic Navier-Stokes Solver (DeHNSSo) solves the harmonic Navier-Stokes equations nonlinearly on domains featuring sharp and smooth spanwise invariant surface features using a generalized grid approach in combination with an embedded boundary method. This allows the user to include the effects of streamwise gradients on flow at a fraction of the cost of DNS.Additional comments including restrictions and unusual features: In DeHNSSo, the equations are solved using direct matrix solvers. As such, memory is treated as a scarce resource. The problem is formulated in a mode-independent manner such that left-hand side matrices need only be computed and stored once despite incorporating nonlinear terms. Additionally, DeHNSSo offers the user the possibility to prescribe inhomogeneous boundary conditions to introduce and solve the receptivity problem or manipulate instabilities. Due to the double Fourier expansion, the solver is restricted to spanwise and temporally periodic problems.

An Experimental Study on the Hardness, Inter Laminar Shear Strength, and Water Absorption Behavior of Habeshian Banana Fiber Reinforced Composites

ABSTRACT The current study examines the effect of NaOH treatment on the hardness, inter-laminar shear strength (ILSS) and water absorption behavior of epoxy composites reinforced with banana pseudostem fibers. Using the hand-lay-up method, six distinct samples are created that are composed of layers of woven and short banana fibers in both a plain and hybrid form. Plain- treated woven composites reveal the highest hardness and ILLS properties followed by the hybrid and short fiber composites. The random orientation of the fiber structure in short fiber composites results in the largest moisture absorption; this behavior is further supported by elucidating the kinetic parameters and diffusion coefficient parameters. SEM analysis confirms the improved surface of the NaOH-treated composite material.

Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction.

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.

Lack of Laminar Shear Stress Facilitates the Endothelial Uptake of Very Small Superparamagnetic Iron Oxide Nanoparticles by Modulating the Endothelial Surface Layer.

To study whether the absence of laminar shear stress (LSS) enables the uptake of very small superparamagnetic iron oxide nanoparticles (VSOP) in endothelial cells by altering the composition, size, and barrier function of the endothelial surface layer (ESL). A quantitative particle exclusion assay with living human umbilical endothelial cells using spinning disc confocal microscopy revealed that the dimension of the ESL was reduced in cells cultivated in the absence of LSS. By combining gene expression analysis, flow cytometry, high pressure freezing/freeze substitution immuno-transmission electron microscopy, and confocal laser scanning microscopy, we investigated changes in ESL composition. We found that increased expression of the hyaluronan receptor CD44 by absence of shear stress did not affect the uptake rate of VSOPs. We identified collagen as a previously neglected component of ESL that contributes to its barrier function. Experiments with inhibitor halofuginone and small interfering RNA (siRNA) demonstrated that suppression of collagen expression facilitates VSOP uptake in endothelial cells grown under LSS. The absence of laminar shear stress disturbs the barrier function of the ESL, facilitating membrane accessibility and endocytic uptake of VSOP. Collagen, a previously neglected component of ESL, contributes to its barrier function.

Mimicking kidney flow shear efficiently induces aggregation of LECT2, a protein involved in renal amyloidosis

Aggregation of leukocyte cell-derived chemotaxin 2 (LECT2) causes ALECT2, a systemic amyloidosis that affects the kidney and liver. Previous studies established that LECT2 fibrillogenesis is accelerated by loss of its bound zinc ion and stirring/shaking. These forms of agitation create heterogeneous shear conditions, including air-liquid interfaces that denature proteins, that are not present in the body. Here, we determined the extent to which a more physiological form of mechanical stress—shear generated by fluid flow through a network of narrow channels—drives LECT2 fibrillogenesis. To mimic blood flow through the kidney, where LECT2 and other proteins form amyloid deposits, we developed a microfluidic device consisting of progressively branched channels narrowing from 5 mm to 20 μm in width. Shear was particularly pronounced at the branch points and in the smallest capillaries. Aggregation was induced within 24 h by shear levels that were in the physiological range and well below those required to unfold globular proteins such as LECT2. EM images suggested the resulting fibril ultrastructures were different when generated by laminar flow shear vs. shaking/stirring. Importantly, results from the microfluidic device showed the first evidence that the I40V mutation accelerated fibril formation and increased both size and density of the aggregates. These findings suggest that kidney-like flow shear, in combination with zinc loss, acts in combination with the I40V mutation to trigger LECT2 amyloidogenesis. These microfluidic devices may be of general use for uncovering mechanisms by which blood flow induces misfolding and amyloidosis of circulating proteins.

Interlaminar shear and impact properties of particle reinforced jute fiber/epoxy hybrid composites

In today’s world, there is a growing emphasis on using fiber-reinforced composites carefully across diverse sectors like automotive, construction, machinery and appliances. These materials are valued for their capacity to be efficiently repurposed, recycled or disposed of with minimal ecological consequences. Thus, integrating sustainable, eco-friendly and environmental mindful approaches into developing new materials and processes has become increasingly imperative. This study aims to analyze the impact strength, inter laminar shear strength and water absorption capacity of the jute fiber composite filled with the particles like alumina (Al2O3), boron carbide (B4C) and silicon carbide (SiC). The response surface methodology (RSM), employing three levels and three parameters, enables the identification of distinct combinations of input parameters essential for the fabrication of suitable polymer composites. The effects of process factors on interlaminar shear strength (ILSS), impact strength and % weight increase are examined. For each output measures, the connotation of the input parameters is determined by analysis of variance (ANOVA). To establish multiple performance indexes, a hybrid model called adaptive neuro-fuzzy inference system (ANFIS) based on Grey theory is developed. The model’s capability is validated and the results confirm the effective prediction of the preferred performance indicator.