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Abstract When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment‐induced anoikis and fluidic shear stress (SS)‐mediated apoptosis. Circulatory treatment, which can make CTCs detached but also generate SS, can increase metastasis of cancer cells. To identify SS‐specific mechanosensors without detachment impacts, a microfluidic circulatory system is used to generate arteriosus SS and compare transcriptome profiles of circulating lung cancer cells with suspended cells. Half of the cancer cells can survive SS damage and show higher invasion ability. Mesotrypsin (PRSS3), protease‐activated receptor 2 (PAR2), and the subunit of activating protein 1, Fos‐related antigen 1 (FOSL1), are upregulated by SS, and their high expression is responsible for promoting invasion and metastasis. SS triggers PRSS3 to cleave the N‐terminal inhibitory domain of PAR2 within 2 h. As a G protein‐coupled receptor, PAR2 further activates the Gαi protein to turn on the Src‐ERK/p38/JNK‐FRA1/cJUN axis to promote the expression of epithelial–mesenchymal transition markers, and also PRSS3, which facilitates metastasis. Enriched PRSS3, PAR2, and FOSL1 in human tumor samples and their correlations with worse outcomes reveal their clinical significance. PAR2 may serve as an SS‐specific mechanosensor cleavable by PRSS3 in circulation, which provides new insights for targeting metastasis‐initiating CTCs.

Magnesium (Mg)-based materials have excellent potential for application in biodegradable vascular stents. Before application, all these materials need to be screened and optimized, especially the screening of corrosion resistance, which is one of the key indicators for stent material screening. Based on the characteristics of the structure of the stent, we focus on the study of the corrosion and degradation behavior of the micron-scale stent struts in the simulated in vivo environment. The struts are simplified into Mg-based wires, and a microfluidic system is established to provide near physiological conditions. A flow-induced shear stress (FISS) of approximately 0.68 Pa close to the wall shear stress of the human coronary artery is applied to the sample surface relying on the microfluidic system. The degradation behaviors of Mg-based wire samples close to the size of struts are studied simultaneously parallel under FISS conditions using this microfluidic system. The immersion test and in vivo experiments demonstrated the feasibility of this microfluidic system for studies of the degradation behavior of Mg-based materials under simulated physiological conditions. In addition, it was also investigated that the effect of degradation products produced under dynamic conditions on vascular cell behavior. The results show that the degradation rate is significantly accelerated under the effect of FISS in the in vitro study, the degradation rate is obviously higher than that in vivo, and AZ31 has the fastest degradation rate compared with pure magnesium and Mg–Zn–Y–Nd alloys. Taken together, this microfluidic system can be used to evaluate and screen the corrosion resistance of Mg-based materials, providing a basis for the design and optimization of Mg-based cardiovascular stent materials.

Introduction: Generating physiologically relevant red blood cell extracellular vesicles (RBC-EVs) for mechanistic studies is challenging. Herein, we investigated how to generate and isolate high concentrations of RBC-EVs in vitro via shear stress and mechanosensitive piezo1 ion channel stimulation.Methods: RBC-EVs were generated by applying shear stress or the piezo1-agonist yoda1 to RBCs. We then investigated how piezo1 RBC-EV generation parameters (hematocrit, treatment time, treatment dose), isolation methods (membrane-based affinity, ultrafiltration, ultracentrifugation with and without size exclusion chromatography), and storage conditions impacted RBC-EV yield and purity. Lastly, we used pressure myography to determine how RBC-EVs isolated using different methods affected mouse carotid artery vasodilation.Results: Our results showed that treating RBCs at 6% hematocrit with 10 µM yoda1 for 30 min and isolating RBC-EVs via ultracentrifugation minimized hemolysis, maximized yield and purity, and produced the most consistent RBC-EV preparations. Co-isolated contaminants in impure samples, but not piezo1 RBC-EVs, induced mouse carotid artery vasodilation.Conclusion: This work shows that RBC-EVs can be generated through piezo1 stimulation and may be generated in vivo under physiologic flow conditions. Our studies further emphasize the importance of characterizing EV generation and isolation parameters before using EVs for mechanistic analysis since RBC-EV purity can impact functional outcomes.

Water-soluble polymers are used to improve drilling operations to ensure that oil and gas wells are drilled in less time and completed with minimized formation damage. However, excessive utilization of these polymers additives may have implication on the drilling outcomes. In this work, drilling fluids comprising of different compositions of polyanionic cellulose (PAC), and starch; and a constant amount of bentonite were formulated to examine the effects of excessive use of each additive or their combinations in a water-based drilling fluid (WBDF). The fluid properties were further investigated at low pressure and low temperature (LPLT) as well as high pressure and high temperature (HPHT). The results suggest that the viscosities of the fluid are not only dependent on the shear rate, shear stress, and composition but also on the temperature and pressure. Model plots of shear stress (Pa) against shear rate (s−1) using the Power law, Bingham plastic and Herschel-Bulley shows that all composition have low viscosity and low yield point. Increasing the amount of additive increases, the equivalent circulating density (ECD) which may increase differential sticking and consequent formation damage. [ABSTRACT FROM AUTHOR]

Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow (p < 0.01 each). The HS expression was higher under laminar flow after a 1 day (p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down (p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders (p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis. [ABSTRACT FROM AUTHOR]

Water migration often occurs in the permafrost slopes during seasonal variations. The water can be accumulated in the vicinity of the freezing front, and then congealed into ice, due to the influence of gravitational and temperature fields. The underlying ice layer was gradually formed with the increase of ice thickness and area. The interface between the ice layer and the overlying frozen soil can play a crucial role in the stability of the permafrost slope. The mechanical behaviors of ice-frozen soil interface can provide the theoretical support for the stability assessment of permafrost slopes over the long term. This research aims to investigate the mechanical properties of the ice-frozen soil interface. A series of direct shear tests were conducted under the temperature of −3 ℃. The shear stresses of the ice-frozen soil interface and the ice-soil particles interface were investigated under different normal stresses, initial water contents, and initial void ratios of the frozen soil. The experimental results showed that the shear stress of the ice-soil particles interface exhibited the hardening behavior, and then increased with the decreasing void ratio of the frozen soil. Softening behavior was found in the shear stress of the ice-frozen soil interface, particularly under lower normal stresses. The shear stress also increased with the increasing initial water content of the frozen soil. The structural coefficient, damage variable, and structural strength of the ice-frozen soil interface were defined, according to the mechanical properties and the failure evolution of the ice-soil particles interface and ice-frozen soil interface. There was an increase in the shear displacement corresponding to the structural coefficient peak point of the icefrozen soil interface with the increase of initial water content. Furthermore, the initial water content of frozen soil increased from 14% to 18%, while the shear displacement increased by 32.7%, 41.3%, and 52.1%, respectively, when the initial void ratios of frozen soil was 1.0, 0.8, and 0.6. A nonlinear elastic damage model was established to consider the bonding characteristics of ice crystals at the ice-frozen soil interface using the Duncan-Chang model, where the tangent stiffness was obtained. The calculation results demonstrate that the shear stress curve suddenly decreased after reaching the peak strength under low normal stress, when the ice content at the interface was high, indicating the noticeable brittleness interface. The mechanical properties of the ice –frozen soil interface shifted gradually from brittleness to plasticity, as the normal stress increased. There was the significant decrease in the magnitude of the shear stress after the peak strength. Therefore, the inhibitory effect of the increasing normal stress on the brittleness failure of the ice-frozen soil interface. The calculation was matched better with the experimental before the peak shear stress. By contrast, the decrease rate of the calculated shear stress curve was significantly lower than the experimental after the peak strength. The tangent stiffness of the interface increased with the increase of normal stress under the same initial void ratio and water content of the frozen soil. The normal stress increased from 50 to 200 kPa, while the tangential stiffness peak point of the interface increased by 63.7%, when the initial void ratio and water content of frozen soil were 1.0, and 18%, respectively. The increasing normal stress was induced a shear movement of soil particles at the ice-frozen soil interface, thus promoting the pore healing and strengthening the interface. Conversely, once the normal stresses were the same, the tangent stiffness of the interface increased with the increase of initial water content of the frozen soil, as the shear displacement was smaller than u0 . While the shear displacement was larger than u0, the tangent stiffness gradually decreased with the increase of shear displacement and approaches zero. [ABSTRACT FROM AUTHOR]

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of lowdose MTX on the vascular endothelium. Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels. Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites. Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium. [ABSTRACT FROM AUTHOR]

The cerebrovascular blood vessels feed necessary agents such as oxygen, glucose, and so forth. to the brain which maintains the smooth functioning of the human body. However, the blood–brain barrier as a vascular border restricts the entry of drugs that can be necessary for the treatment of neurological disorders. The fluid shear stress in the cerebrovascular blood vessels may regulate the drug delivery in the interface between the cerebrovascular blood vessels and the brain. The intensity of influence by various factors that affects the shear stress in the cerebrovascular blood vessels is scarcely addressed in the present study. A hybrid approach of computational fluid dynamics and Taguchi analysis is proposed to evaluate the influence of various geometrical and operating factors on the shear stress in the microfluidic cerebrovascular channel. Furthermore, the non‐Newtonian behavior of blood flow is considered to evaluate the shear stress in the microfluidic cerebrovascular channel. The Newtonian and six non‐Newtonian fluids models of Carreau, Carreau–Yasuda, Casson, Cross, Ostwald–de Waele, and Herschel–Bulkley are numerically tested under various conditions of the flow rate, width, and height of the channel to find the viscosity influence on the shear stress. The Taguchi analysis consisting of range and variance analyses is applied to the L16 orthogonal array to evaluate the effect of various factors on shear stress in terms of influence order, range, F value, and percentage contribution. The parameters for the considered six non‐Newtonian fluid models are proposed to accurately map the viscosity behavior with shear strain compared to the actual blood flow behavior. The Newtonian, Carreau, and Carreau–Yasuda non‐Newtonian fluid models are found accurately with maximum errors between the experimental and numerical shear stress results as 2.17%, 1.30%, and 1.48%, respectively. The shear stress decreases with an increase in the width and height of the channel and a decrease in the viscosity for all flow rates. The porosity is evaluated as a highly influential factor followed by the flow rate, width, and height of the channel in decreasing order based on their effects on the shear stress. The modified shear stress equation is proposed with an accuracy of 0.96 by integrating the effect of porosity in addition to width, height, flow rate, and viscosity. The in‐vitro microfluidic cerebrovascular model could be designed and manufactured based on the proposed results on influence order, F value, and percentage contribution of various factors in direction of achieving the in‐vivo level shear stress. [ABSTRACT FROM AUTHOR]

It is essential to design a multifunctional well‐controlled platform to transfer mechanical cues to the cells in different magnitudes. This study introduces a platform, a miniaturized bioreactor, which enables to study the effect of shear stress in microsized compartmentalized structures. In this system, the well‐established cell encapsulation system of liquefied capsules (LCs) is used as microbioreactors in which the encapsulated cells are exposed to variable core viscosities to experience different mechanical forces under a 3D dynamic culture. The LC technology is joined with electrospraying to produce such microbioreactors at high rates, thus allowing the application of microcapsules for high‐throughput screening. Using this platform for osteogenic differentiation as an example, shows that microbioreactors with higher core viscosity which produce higher shear stress lead to significantly higher osteogenic characteristics. Moreover, in this system the forces experienced by cells in each LC are simulated by computational modeling. The maximum wall shear stress applied to the cells inside the bioreactor with low, and high core viscosity environment is estimated to be 297 and 1367 mPa, respectively, for the experimental setup employed. This work outlines the potential of LC microbioreactors as a reliable in vitro customizable platform with a wide range of applications. [ABSTRACT FROM AUTHOR]

This paper presents an innovative experimental setup that employs the principles of audio technology to subject adherent cells to rhythmic vertical vibrations. We employ a novel approach that combines three-axis acceleration measurements and particle tracking velocimetry to evaluate the setup's performance. This allows us to estimate crucial parameters such as root mean square acceleration, fluid flow patterns, and shear stress generated within the cell culture wells when subjected to various vibration types. The experimental conditions consisted of four vibrational modes: No Vibration, Continuous Vibration, Regular Pulse, and Variable Pulse. To evaluate the effects on cells, we utilized fluorescence microscopy and a customized feature extraction algorithm to analyze the F-actin filament structures. Our findings indicate a consistent trend across all vibrated cell cultures, revealing a reduction in size and altered orientation (2D angle) of the filaments. Furthermore, we observed cell accumulations in the G1 cell cycle phase in cells treated with Continuous Vibration and Regular Pulse. Our results demonstrate a negative correlation between the magnitude of mechanical stimuli and the size of F-actin filaments, as well as a positive correlation with the accumulations of cells in the G1 phase of the cell cycle. By unraveling these analyses, this study paves the way for future investigations and provides a compelling framework for comprehending the intricate cellular responses to rhythmic mechanical stimulation. [ABSTRACT FROM AUTHOR]

Systemic endothelial dysfunction holds particular relevance in the context of preeclampsia because it has been associated with circulating placental factors, maternal major symptoms, and later cardiovascular risk. Studies profiling changes in preeclamptic maternal endothelial function have been explored for a long time but in vivo and in vitro models both have several limitations. Shear stress is a hemodynamic force that strongly regulates endothelial function and dysfunction. This biomechanical force is not considered by the majority of in vitro studies on this topic because they mostly utilize static endothelial cell cultures. The combination of advances in biotechnology and biomolecular approaches can improve our knowledge of the missing links between circulating biomarkers and maternal endothelial dysfunction in preeclampsia. This will provide a better understanding of its pathophysiology and lead to the identification of potential therapeutic targets. Preeclampsia, one of the main hypertensive disorders of pregnancy, is associated with circulating factors released by the ischemic placenta accompanied by systemic endothelial dysfunction. The etiology of preeclampsia remains poorly understood although it is associated with high maternal and fetal mortality and increased cardiovascular disease risk. Most cell model systems used for studying endothelial dysfunction have not taken into account hemodynamic physical factors such as shear-stress forces which may prevent extrapolation of cell data to in vivo settings. We overview the role of hemodynamic forces in modulating endothelial cell function and discuss strategies to reproduce this biological characteristic in vitro to improve our understanding of endothelial dysfunction associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Mineral dehydration in the subduction zone enormously affects Earth's geodynamics and the global geochemical cycles of elements. This work uses Raman spectroscopy and X-ray diffraction to investigate the dehydration process of antigorite under compression and shear loading conditions in a rotational diamond anvil cell (RDAC) at room temperature. In order to compare the shear effects, T301 stainless steel and Kapton plastic are applied as the gasket materials. In the experiment using a high-strength T301 stainless steel gasket, two new broad OH-stretching peaks of H2O and H3O2− appear at 3303 and 3558 cm−1, respectively, at 1.7 GPa. The original sharp OH-stretching peaks of antigorite at 3668 and 3699 cm−1 remain, while the central pressure is increased to 8.0 GPa, and the largest pressure gradient is about 2.5 GPa in the sample chamber. In another experiment with a low-strength gasket of Kapton plastic, two new OH-stretching broad peaks of H2O and H3O2− also start to appear at 3303 and 3558 cm−1, respectively, at a lower pressure of 0.3 GPa, but the original sharp OH-stretching peaks of antigorite at 3668 and 3699 cm−1 almost completely vanish as the central pressure reaches 3.0 GPa, with the largest pressure gradient at around 4.8 GPa. The comparison between the two experiments shows that antigorite is easier to dehydrate in the chamber of a Kapton plastic gasket with a larger gradient of shear stress. However, its axial compression stress is lower. The high-pressure Raman spectra of MgO2(OH)4 octahedron and SiO4 tetrahedron in the low wavenumber zones (100–1200 cm−1) combined with the micro-beam X-ray diffraction spectrum of the recovered product strongly support the structural breakdown of antigorite. This investigation reveals that the water-bearing silicate minerals have strong shear dehydration in the cold subduction zone of the plate, which has important applications in predicting the physical and chemical properties of subduction zones and deducing the rate of plate subduction. [ABSTRACT FROM AUTHOR]

Because a variety of fuels can be burned during the combustion process, CFB boilers have a very wide range of applications in coal-fired power plants. The uneven distribution of homogeneity between the air and the particles and the large volume fraction in some locations could result in erosion of the furnace walls. In order to decrease the impacts of erosion, the ring baffle feature is added to the furnace wall. In order to compare data variations in the form of ring baffle depth with variations of 0.15 m, 0.3 m, and 0.45 m as well as the number of ring baffles 1 and 2, the CFD approach is utilized. The factors tested included pressure drop distribution, particle volume fraction distribution, particle axial and radial velocity distribution, and shear stress. With a maximum value of 0.012 for the volume percent, the variation of two ring baffles with a depth of 0.3 m each offered the best results in terms of homogeneity inside the CFB of the boiler. Additionally, a pressure decrease of 7.38 kPa was seen due to the maximum axial and radial speeds that were measured at the ring baffle, which were 27.1 m/s and 2.46 m/s, respectively. Additionally, the furnace wall can avoid probable erosion thanks to the shear stress contours, which mirror the volume percentage of particles. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the function of Cx43 in the endothelial-to-mesenchymal transition (EndMT) process of endothelial cells (ECs) and to explore the potential signaling pathways underlying these functions. Methods: ECs were extracted from rat aorta. ECs were transfected with Cx43 cDNA and Cx43 siRNA and then exposed to 5 or 12 dyne/cm2. Immunofluorescence staining was used to detect the expression of SM22α, Cx43, and acetylated α-tubulin in ECs. Western blotting was used to detect the protein expression of α-SMA, CD31, Cx43, H1-calponin, Ift88, and p-smad3 in ECs. Results: The expression of αSMA, SM22α, and Cx43 was significantly increased, and CD31 was markedly decreased in ECs treated with laminar shear stress at 5 dyn/cm2. The Cx43 cDNA transfection could induce the expression of SM22α or H1-calponin and attenuate CD31 expression in ECs. Also, Cx43 overexpression harms cilia formation in ECs exposed to 5 dyn/cm2, accompanied with the regulated Ift88 and smad signaling. Conclusions: This study found that laminar shear stress at 5 dyn/cm2 would increase the expression of Cx43 to facilitate the EndMT process of ECs, associated with morphological changes in primary cilia and the decreased expression of Ift88 in ECs. [ABSTRACT FROM AUTHOR]

Introduction: Branch atheromatous disease (BAD) is a type of cerebral infarction caused by stenosis or occlusion at the entrance of the penetrating branch due to the presence of plaque. Despite its clinical significance, it is not clear how these plaques are formed. Focal geometrical characteristics are expected to be as important as vascular risk factors in the development of atherosclerosis. This study aimed to analyze the association between middle cerebral artery (MCA) geometric features and the onset of BAD. Shear stress results from the blood flow exerting force on the inner wall of the vessels and places with low wall shear stress may be prone to atherosclerosis. At the curvature of blood vessels, the shear stress is weak on the inside of the curve and plaque is likely to form. When this is applied to the MCA M1 segment, downward type M1 is likely to form plaques on the superior side. Because the lenticulostriate artery usually branches off from the superior side of the MCA M1 segment, in downward type M1, a plaque is likely to be formed at the entrance of the penetrating branch, and for that reason, BAD is likely to onset. Methods: We retrospectively reviewed hospitalized stroke patients with BAD and investigated the morphology of their MCA using magnetic resonance imaging. The M1 segment was classified as straight or curved. Additionally, we compared the difference between the symptomatic and the asymptomatic side. Data regarding patients' medical history were also collected. Results: A total of 56 patients with lenticulostriate artery infarctions and BAD were analyzed. On the symptomatic side, downward type M1 accounted for the largest proportion at 44%, whereas on the asymptomatic side, it was the lowest, at 16%. Conclusion: A downward type MCA may be associated with the onset of BAD and the morphological characteristics might affect the site of plaque formation. [ABSTRACT FROM AUTHOR]

The viscosity of lubricating oils is influenced by fly-ash additives and temperature, as they play a crucial role in regulating the viscosity of oils. Fly-ash additives are added to lubricating oils to improve oxidation resistance and prevent deposit formation, which may reduce viscosity loss at high temperatures. This study aimed to investigate the impact of fly-ash additives and temperature on the viscosity of oils B, C, and A. The experimental methodology involved comparing the viscosity of these oils with and without the addition of a 0.5% fly-ash additive. Viscosity measurements were taken at different temperatures. The results showed significant changes in viscosity after incorporating the fly-ash additive. At 25 °C, oils B, C, and A exhibited viscosity increases of 6.2%, 8.1%, and 13.8%, respectively, compared to the samples without the additive. Similarly, at 75 °C, the viscosity increments were 10.2%, 11.5%, and 22.8% for oils B, C, and A, respectively. At 85 °C, the corresponding increments were 11.1%, 16.6%, and 32.8%. These findings highlight the effectiveness of fly-ash additives in reducing the impact of temperature on oil viscosity, with oil A demonstrating the highest efficacy. By adjusting the viscosity of the oil at different temperatures, the fly-ash additives contribute to maintaining stable lubricating performance. Understanding the influence of fly-ash additives and temperature on oil viscosity is crucial for optimizing the performance of lubricants across various temperature conditions. Additionally, this knowledge assists in selecting the appropriate additive ratios for specific applications, thereby ensuring optimal lubricant performance. [ABSTRACT FROM AUTHOR]

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The falling ball method (FBM) is one of the well‐established techniques for measuring the viscosity of Newtonian liquids at the room as well as at elevated temperatures and pressures. Owing to its simplicity and low cost, the possibility of extending its range of application to non‐Newtonian systems including virgin and filled polymer melts, composites, polymer‐solutions, and so forth, is explored here, In this work, theoretical results for the flow of power‐law fluids past a sphere have been used to extract the values of the zero‐shear viscosity and shear‐dependent viscosity in the low‐shear rate limit. The theoretical scheme outlined here has been validated by presenting comparisons with experimental results for scores of polymer solutions for which both falling sphere and rheological data are available in the literature. Indeed, the good correspondence obtained between these two independent data is encouraging and it is thus possible to use the FBM for shear‐thinning systems when the resulting Reynolds numbers are such that the flow is viscosity‐dominated, and the inertial effects are negligible. This implies that the Reynolds number should be ≤ ~1 for shear‐thinning fluids and ≤ ~10−5 for shear‐thickening fluids. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit 'disturbed' flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Longitudinal motion of the carotid arterial wall, as measured with ultrasound, has shown promise as an indicator of vascular health. The underlying mechanisms are however not fully understood. We have found, in in vivo studies, that blood pressure has a strong relation to the antegrade longitudinal displacement in early systole. Further, we have identified that a tapered geometry and the intramural friction in‐between two parts of a vessel wall influence the longitudinal displacement. We therefore studied the interaction between pressure, vessel geometry and intramural friction, tapered and straight ultrasound phantoms in a paralleled hydraulic bench study and corresponding numerical models. Profound antegrade longitudinal motion was induced in the innermost part of both tapered phantoms and the numerical models, but to a lesser extent when intramural friction was increased in the simulations. Strong correlations (R = 0.82–0.96; p < 1e‐3; k = 9.3–14 μm/mmHg) between longitudinal displacement and pulse pressure were found in six of seven regions of interest in tapered phantoms. The motion of the straight phantom and the corresponding numerical model was smaller, on average zero or close to zero. This study demonstrates that tapering of the lumen, low intramural friction, and pressure might be important conducive features to the antegrade longitudinal motion of the arterial wall in vivo. [ABSTRACT FROM AUTHOR]

9p21.3 locus polymorphisms have the strongest correlation with coronary artery disease, but as a noncoding locus, disease connection is enigmatic. The lncRNA ANRIL found in 9p21.3 may regulate vascular smooth muscle cell (VSMC) phenotype to contribute to disease risk. We observed significant heterogeneity in induced pluripotent stem cell-derived VSMCs from patients homozygous for risk versus isogenic knockout or nonrisk haplotypes. Subpopulations of risk haplotype cells exhibited variable morphology, proliferation, contraction, and adhesion. When sorted by adhesion, risk VSMCs parsed into synthetic and contractile subpopulations, i.e., weakly adherent and strongly adherent, respectively. Of note, >90% of differentially expressed genes coregulated by haplotype and adhesion and were associated with Rho GTPases, i.e., contractility. Weakly adherent subpopulations expressed more short isoforms of ANRIL, and when overexpressed in knockout cells, ANRIL suppressed adhesion, contractility, and aSMA expression. These data suggest that variable lncRNA penetrance may drive mixed functional outcomes that confound pathology. [ABSTRACT FROM AUTHOR]

Biomechanics plays a critical role in coronary artery disease development. FSI simulation is commonly used to understand the hemodynamics and mechanical environment associated with atherosclerosis pathology. To provide a comprehensive characterization of patient-specific coronary biomechanics, an analysis of FSI simulation in the spatial and temporal domains was performed. In the current study, a three-dimensional FSI model of the LAD coronary artery was built based on a patient-specific geometry using COMSOL Multiphysics. The effect of myocardial bridging was simulated. Wall shear stress and its derivatives including time-averaged wall shear stress, wall shear stress gradient, and OSI were calculated across the cardiac cycle in multiple locations. Arterial wall strain (radial, circumferential, and longitudinal) and von Mises stress were calculated. To assess perfusion, vFFR was calculated. The results demonstrated the FSI model could identify regional and transient differences in biomechanical parameters within the coronary artery. The addition of myocardial bridging caused a notable change in von Mises stress and an increase in arterial strain during systole. The analysis performed in this manner takes greater advantage of the information provided in the space and time domains and can potentially assist clinical evaluation. [ABSTRACT FROM AUTHOR]

A particle image velocimetry (PIV) technique was used to measure velocity fields of single- and multi-phase fluid flow in a stirred, flat-panel photobioreactor and to validate the computational fluid dynamics (CFD) model. The paper presents the grid independence study, velocity profiles, and shear stresses that were studied under four different operating conditions, i.e. two different agitation speeds, 360 rpm, and 480 rpm, and with or without aeration of 200 ml min−1. The single-phase numerical model showed a correlation in the improved accuracy, and the mesh refinement, even though using a very fine mesh, did not justify the increased computational costs, making a medium mesh more practical. Similarly, the two-phase flow analyses showed a good qualitative agreement with the PIV data. However, PIV measurement in bubbly flows is a challenging task, possibly having large uncertainties due to light effects at the gas–liquid interface. Nevertheless, the large vortex formed near the rotating magnetic stirrer was found to dominate the flow pattern in both, single- and multi-phase, simulations. The effect of the aeration on shear stresses was, naturally, more noticeable with lower agitation speeds. However, with both agitation speeds, the highest shear stresses around the stir bar were found to quickly decay. Thus, the environment in the photobioreactor can be considered appropriate for the cultivation of microalgae. • Coarse to medium meshes provided a satisfactory description of the flow. • A large vortex near the rotating magnetic stirrer dominates the flow. • Distribution of velocity showed a good qualitative agreement with the PIV data. • The magnetic stirrer is the main source of the shear stress. • Shear stress above 2 Pa, critical to microalgae, is within 15% of the PBR volume. [ABSTRACT FROM AUTHOR]

The Vein‐Chip recapitulates CVST Virchow's triad and enables systematic characterization of venous thrombogenesis with respect to fibrin formation and platelet aggregation. Distinct from the arterial setting, platelets universally adhere across the entire CVS Vein‐Chip independent of stenotic geometry and flow disturbance. Intriguingly, fibrin propagates along with the flow direction, but exclusively deposits to the inner vessel wall. Upon inflammatory endothelial injury, fibrin deposition mirrors to the outer vessel wall, but still not in the lumen. Together, the Vein‐Chip promises future applications for personalized thrombotic assessment and monitoring. [ABSTRACT FROM AUTHOR]

The armored layer is crucial for protecting the riverbed. The bed layer of the river is a movable material that protects the material below the surface layer. This study aimed to develop formulas to estimate the thickness of a mobile armor layer with noncohesive materials and establish a correlation between the flow velocity and shear stress under conditions of erosion and sedimentation. The research methods included field measurements, laboratory tests, and numerical simulations. The primary data included grain size gradation profiles, river topography, and flood discharge. The results demonstrated consistency in the behavior of the riverbed under various flood discharge conditions. The fundamental variables affecting the mobile armor thickness included the gradation coefficient (v) and the dimensionless shear stress (0/c). The fundamental novelty of this study is the derivation of the mobile armor layer thickness, which is influenced by grain size and shear stress. The present findings significantly contribute to the design of more efficient and environmentally friendly riverbed protection rather than rigid structures. These results indicated that erosion and sedimentation were primarily influenced by the flow velocity and the applied shear stress above the riverbed. [ABSTRACT FROM AUTHOR]

Except for biochemical effects, suspension state (Sus) is proved to induce epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) mechanically. However, the difference between the effects of the mechanical microenvironment in capillaries (simplified as shear stress (SS) and Sus) and single Sus on EMT is unclear, nor the underlying mechanism. Here, breast tumor cells (BTCs) were loaded with Sus and SS to mimic the situation of CTCs stimulated by these two kinds of mechanics. It was demonstrated that the EMT of BTCs was enhanced by Sus and SS and the mechanotransductor yes-associated protein (YAP) was partially cytoplasmic stored with microRNA (miR)-29b decreased, which was detected by miR sequencing. Though it couldn't possess a feedback regulation, YAP promoted miR-29b expression and posttranscriptionally regulated BTCs EMT through miR-29b, where transforming growth factor β involved. Analysis of clinical database showed that high miR-29b expression was beneficial to high survival rate stabilizing its role of tumor suppressor. This study discovers the mechanism that Sus and SS promote BTCs EMT by YAP through miR-29b posttranscriptionally and highlight the potential of YAP and miR-29b in tumor therapy. The combination of suspension state and shear stress promotes transforming growth factor β involved epithelial-mesenchymal transition by yes-associated protein through microRNA-29b [ABSTRACT FROM AUTHOR]

Shear stress is a frictional drag generated by the flow of fluid, such as blood or interstitial fluid, and plays a critical role in regulating cellular gene expression and functional phenotype. The matricellular CCN family proteins are dynamically regulated by shear stress of different flow patterns, and their expression significantly alters the microenvironment of cells. Secreted CCN proteins mainly bind to several cell surface integrin receptors to mediate their diverse functions in regulating cell survival, function, and behavior. Gene-knockout studies indicate major functions of CCN proteins in the cardiovascular and skeletal systems, the two primary systems in which CCN expressions are regulated by shear stress. In the cardiovascular system, the endothelium is directly exposed to vascular shear stress. Unidirectional laminar blood flow generates laminar shear stress, which promotes a mature endothelial phenotype and upregulates anti-inflammatory CCN3 expression. In contrast, disturbed flow generates oscillatory shear stress, which induces endothelial dysfunction through the induction of CCN1 and CCN2. Shear-induced CCN1 binds to integrin α6β1 and promotes superoxide production, NF-κB activation, and inflammatory gene expression in endothelial cells. Although the interaction between shear stress and CCN4-6 is not clear, CCN 4 exhibits a proinflammatory property and CCN5 inhibits vascular cell growth and migration. The crucial roles of CCN proteins in cardiovascular development, homeostasis, and disease are evident but not fully understood. In the skeletal system, mechanical loading on bone generates shear stress from interstitial fluid in the lacuna-canalicular system and promotes osteoblast differentiation and bone formation. CCN1 and CCN2 are induced and potentially mediate fluid shear stress mechanosensing in osteocytes. However, the exact roles of interstitial shear stress-induced CCN1 and CCN2 in bone are still not clear. In contrast to other CCN family proteins, CCN3 inhibits osteoblast differentiation, although its regulation by interstitial shear stress in osteocytes has not been reported. The induction of CCN proteins by shear stress in bone and their functions remain largely unknown and merit further investigation. This review discusses the expression and functions of CCN proteins regulated by shear stress in physiological conditions, diseases, and cell culture models. The roles between CCN family proteins can be compensatory or counteractive in tissue remodeling and homeostasis. [ABSTRACT FROM AUTHOR]

For three-dimensional multi-layer molecularly thin-film lubrication system with elastic substrates, roles of hysteresis on tribological properties are investigated by using the multiscale simulation method. It is found that multiple stick-slip transitions with/without hysteresis loops appear in a sliding process and form a quasi-periodic progress with lattice distance. For the few-/multi-layer thin-film lubrication system, as the load increases, the hysteresis length monotonously increases/tends to keep constant. The hysteresis is mainly caused by the relaxation of metastable states of solid atoms in the elastic substrates, which delays the system back to its equilibrium states. In the quasi-periodic shearing progress, the effective elastic coefficients and the hysteresis lengths approximately remain unchanged, which reveals that although the hysteresis loops with the same lengths appear in the sliding process, the total systematic energy is still conserved. These findings not only provide a profound understanding of roles of hysteresis in the thin-film lubrication system but also show the effects of film layers and loads on the systematic tribological properties, which are of great significance for practical applications. [ABSTRACT FROM AUTHOR]

The Superconducting Conductor Testing Facility, which is developed to evaluate the reliability of engineering technology and safe operation in fusion reactor operation environment, is under engineering design by ASIPP. In case of an emergency shut-down like in succession of a quench, the voltage across the coil may rise to about 2.5 kV. The facility has to be reliably insulated. In this study, we present the preliminary design of the insulation system of the Superconducting Conductor Testing Facility, which includes turn and ground insulation. Since the magnet of the facility adopts the manufacturing process of “Wind&React”, the turn insulation material should withstand a heat treatment with temperature up to 650 °C. The insulation system is composed of S-glass fiber reinforced tape and vacuum-pressure impregnated in a DGEBF epoxy system. The mechanical properties are being subjected to investigations with respect to the design requirements and operating conditions. The test results are analyzed to verify the feasibility of the insulation system design. [ABSTRACT FROM AUTHOR]

Fill-finish of parenteral formulations represents a crucial step in the pharmaceutical industry that necessitates careful monitoring of product stability down the line. Shear stress and interfacial stress are two elements that threaten product stability, the respective contributions of which are still up for debate. This article focuses on the analysis of shear stress in the sampling phase of the filling line. Specifically, Computational Fluid Dynamics (CFD) simulations were employed to determine the shear stress distribution experienced by a protein-based parenteral drug as it passes through sampling fittings of various shapes under laminar and turbulent regime conditions. Rather than seeking the specific mechanism triggering the destabilization of a product, an attempt was made to analyze the fluid dynamics within these fittings and offer further understanding of the resulting shear stress. In addition, information was collected on the product path within the fittings, which allowed the identification of equations suitable for describing the shear stress distribution. The proposed approaches made it possible to consider the actual flowrate subjected to a given shear stress at a given time. Finally, a comparison was drawn with respect to the fluid dynamics within classical straight tubing to outline differences. This study revealed that the shear stress experienced within the fittings was higher than that in the tubing. Moreover, significant differences were reported in the T-fitting case under turbulent conditions. [ABSTRACT FROM AUTHOR]

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action. [ABSTRACT FROM AUTHOR]

Gaining insight into the in situ receptor–ligand binding is pivotal for revealing the molecular mechanisms underlying the physiological and pathological processes and will contribute to drug discovery and biomedical application. An important issue involved is how the receptor–ligand binding responds to mechanical stimuli. This review aims to provide an overview of the current understanding of the effect of several representative mechanical factors, such as tension, shear stress, stretch, compression, and substrate stiffness on receptor–ligand binding, wherein the biomedical implications are focused. In addition, we highlight the importance of synergistic development of experimental and computational methods for fully understanding the in situ receptor–ligand binding, and further studies should focus on the coupling effects of these mechanical factors. [ABSTRACT FROM AUTHOR]

Membrane bioreactors (MBRs) are high-tech systems for water recycling and reusing of unconventional water resources such as municipal wastewater. However, the fouling of polymeric membranes is the main impediment to the market development of MBR. The polyolefin-based membranes are subjected to more severe organic fouling than other hydrophilic membranes due to their inherent strong hydrophobic properties, therefore, proposing efficient, fast, and economic fouling mitigation methods is vital for durable and long-standing performance. In this research, the hydrodynamics of a lab-scale membrane bioreactor with different configurations of aerators and nozzle sizes were used to investigate the air scouring efficiency. It was gained that aerators with higher air flow rates, e.g., 5.5 m/s can produce slug bubbles which are capable of foulant removal from the membrane surface. In comparison with a non-central aerator, the satisfactory scouring zone of the central aerator is narrow and the edge nozzles on both sides of the aerator are blocked. Under constant air flow rate, when the inlet air is injected into the aerator from two and three points, not only the end nozzles are blocked but also the liquid is penetrated into the aerator and the shear stress on the membrane surface decreased to 0.765 Pa. In the case of the non-central aerator, the satisfactory scouring zone becomes wider and neither nozzle blockage nor liquid penetration down to the aerator has occurred. The distribution of bubbles was optically evaluated by video imaging through the transparent plexiglass tank using aerators with different inlet flow rates and various configurations. Numerical simulations and related experimental analyses demonstrated that air inlet velocity has an important role in creating larger slug bubbles. It was shown that a non-central aerator in which the central nozzle in front of the inlet air stream is blocked, produces slug bubbles and sufficient air scoring on the flat sheet membrane. Configuration of a non-central aerator with 4 nozzles not only increased the satisfactory zone of each aerator without blockage of edge nozzles and liquid penetration into the aerator but also provided a higher shear rate over 1.104 Pa under a constant flow rate, which consequently removed the foulant from the membrane surface. [ABSTRACT FROM AUTHOR]

Suspension cultures are widely used for cell expansion in regenerative medicine and production. Shaking culture is one of the useful suspension culture methods that ensures gentle agitation. There are other shaking methods, including orbital shaking, reciprocating, and rocking; however, optimizing the shaking conditions for each method to meet cell culture requirements is time-consuming. In this study, we used a particle-tracking-based strategy for optimizing the agitation conditions. When the average accelerations of aggregates were calculated, high acceleration occurred periodically, and acceleration of the aggregates in orbital shaking was stable. Furthermore, the number of dead cells correlated with the average time of acceleration. We observed that cell growth was ideally maintained by factors such as optimal acceleration, aggregate formation, and cell death. These results indicate that the image-based analyses of aggregates help optimize the agitation conditions for the shaking suspension culture of induced pluripotent stem cells (iPSCs). [ABSTRACT FROM AUTHOR]

Cartilage microtissues are promising tissue modules for bottom up biofabrication of implants leading to bone defect regeneration. Hitherto, most of the protocols for the development of these cartilaginous microtissues have been carried out in static setups, however, for achieving higher scales, dynamic process needs to be investigated. In the present study, we explored the impact of suspension culture on the cartilage microtissues in a novel stirred microbioreactor system. To study the effect of the process shear stress, experiments with three different impeller velocities were carried out. Moreover, we used mathematical modeling to estimate the magnitude of shear stress on the individual microtissues during dynamic culture. Identification of appropriate mixing intensity allowed dynamic bioreactor culture of the microtissues for up to 14 days maintaining microtissue suspension. Dynamic culture did not affect microtissue viability, although lower proliferation was observed as opposed to the statically cultured ones. However, when assessing cell differentiation, gene expression values showed significant upregulation of both Indian Hedgehog (IHH) and collagen type X (COLX), well known markers of chondrogenic hypertrophy, for the dynamically cultured microtissues. Exometabolomics analysis revealed similarly distinct metabolic profiles between static and dynamic conditions. Dynamic cultured microtissues showed a higher glycolytic profile compared with the statically cultured ones while several amino acids such as proline and aspartate exhibited significant differences. Furthermore, in vivo implantations proved that microtissues cultured in dynamic conditions are functional and able to undergo endochondral ossification. Our work demonstrated a suspension differentiation process for the production of cartilaginous microtissues, revealing that shear stress resulted to an acceleration of differentiation towards hypertrophic cartilage. [ABSTRACT FROM AUTHOR]

This study characterized biofilm formation of various Salmonella strains on common processing plant surface materials (stainless steel, concrete, rubber, polyethylene) under static and fluidic shear stress conditions. Surface-coupons were immersed in well-plates containing 1 mL of Salmonella (6 log CFU/mL) and incubated aerobically for 48 h at 37 °C in static or shear stress conditions. Biofilm density was determined using crystal violet assay, and biofilm cells were enumerated by plating on tryptic soy agar plates. Biofilms were visualized using scanning electron microscopy. Data were analyzed by SAS 9.4 at a significance level of 0.05. A surface–incubation condition interaction was observed for biofilm density (p < 0.001). On stainless steel, the OD600 was higher under shear stress than static incubation; whereas, on polyethylene, the OD600 was higher under static condition. Enumeration revealed surface–incubation condition (p = 0.024) and surface–strain (p < 0.001) interactions. Among all surface–incubation condition combinations, the biofilm cells were highest on polyethylene under fluidic shear stress (6.4 log/coupon; p < 0.001). Biofilms of S. Kentucky on polyethylene had the highest number of cells (7.80 log/coupon) compared to all other strain–surface combinations (p < 0.001). Electron microscopy revealed morphological and extracellular matrix differences between surfaces. Results indicate that Salmonella biofilm formation is influenced by serotype, surface, and fluidic shear stress. [ABSTRACT FROM AUTHOR]

The importance of the microenvironment is widely recognized as it regulates not only malignant cell behavior but also drug sensitivity. The cancer cell microenvironment is composed of biological, physical and chemical elements, and simultaneous reproduction of these three elements are important conditions investigated in cancer research. In the present study, we focused on the epidemiological and anatomical specificities of endometrioid carcinoma, obesity (biological), fluid flow (physical) and anticancer agents (chemical) to target the specific microenvironmental elements of endometrioid carcinoma. To elucidate the individual effects of these elements on endometrioid carcinoma and to investigate the relationships between these factors, we developed an adipose tissue fragments (ATFs)-embedded cell disc under a rotational culture method to generate carcinoma-stroma interactions and to create fluid flow. ATFs and fluid flow individually or synergistically influenced proliferative cellular behavior and the morphological changes underlying endometrioid carcinoma. ATFs and fluid flow also governed the expression of extracellular signal-regulated kinase and p38 signaling synergistically or individually, depending on the endometrioid carcinoma cell type. Adipose tissue induced chemoresistance to cis-diamminedichloro-platinum (CDDP) in endometrioid cancer, but the resistance effect was abolished by fluid flow. Thus, a simple reconstructed model was established to investigate three elements of the microenvironment of endometrioid carcinoma in vitro. This culture model unequivocally demonstrated the individual and synergistic effects of the three elements on endometrioid carcinoma. This new culture model is a promising tool for elucidating the mechanisms underlying endometrioid carcinoma and for developing further treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: Wind speeds over different averaging times significantly influence the assessment of wind erosivity, which describes the capacity of wind to cause soil erosion. This study aims to quantify this time interval effect on wind erosivity assessment. Methods: This study took the wind erosion region of northern China as the study area and compared the changes in wind erosivity indexes (including wind-generated near-surface shear stress and drift potential (DP)) over different averaging times based on wind speed conversion. Results: Both DP and the effective shear stress (generated by sand-driving wind) decreased as the averaging time increased. On the contrary, total shear stress (generated by all the wind) exhibited an opposite trend and is much higher than effective shear stress. Compared to DP, near-surface shear stress can better reflect the erosion capacity of wind on the land surface. This is because the calculation of near-surface shear stress considered the differences in land surface aerodynamic properties. Land surface properties play an important role in the assessment of wind erosivity. Conclusion: Wind erosivity will be underestimated when wind speed with a larger averaging time is used. Wind speed below the threshold that drives sand transport should be eliminated to improve the accuracy of wind erosivity assessment. Surface properties are important factors influencing wind erosivity evaluation. Results from this study will provide a basis for the establishment of wind erosion force conversion models over different averaging times, and provide accurate data support for sand control engineering. [ABSTRACT FROM AUTHOR]

Blood flow produces shear stress that homeostatically regulates the phenotype of pulmonary endothelial cells, exerting antiinflammatory and antithrombotic actions and maintaining normal barrier function. Hypoxia due to diseases, such as chronic obstructive pulmonary disease (COPD), causes vasoconstriction, increased vascular resistance, and pulmonary hypertension. Hypoxia-induced changes in endothelial function play a central role in the development of pulmonary hypertension. However, the interactive effects of hypoxia and shear stress on the pulmonary endothelial phenotype have not been studied. Human pulmonary microvascular endothelial cells were cultured in normoxia or hypoxia while subjected to physiological shear stress or in static conditions. Unbiased proteomics was used to identify hypoxia-induced changes in protein expression. Using publicly available single-cell RNA sequencing datasets, differences in gene expression between the alveolar endothelial cells from COPD and healthy lungs were identified. Sixty proteins were identified whose expression changed in response to hypoxia in conditions of physiological shear stress but not in static conditions. These included proteins that are crucial for endothelial homeostasis (e.g., JAM-A [junctional adhesion molecule A], ERG [ETS transcription factor ERG]) or implicated in pulmonary hypertension (e.g., thrombospondin-1). Fifty-five of these 60 have not been previously implicated in the development of hypoxic lung diseases. mRNA for 5 of the 60 (ERG, MCRIP1 [MAPK regulated corepressor interacting protein 1], EIF4A2 [eukaryotic translation initiation factor 4A2], HSP90AA1 [heat shock protein 90 alpha family class A member 1], and DNAJA1 [DnaJ Hsp40 (heat shock protein family) member A1]) showed similar changes in the alveolar endothelial cells of COPD compared with healthy lungs in females but not in males. These data show that the proteomic responses of the pulmonary microvascular endothelium to hypoxia are significantly altered by shear stress and suggest that these shear-hypoxia interactions are important in the development of hypoxic pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

Stirred suspension culture is becoming a popular method for expanding human pluripotent stem cells (hPSCs). While stirring generates adequate fluid motions to lift the cells and facilitates mass transfers (of nutrients, dissolved gases, and metabolic wastes), excessive stirring could impose hydrodynamic forces deleterious for the growth of the cells. In this study, computational fluid dynamics (CFD) simulations were performed to first investigate hydrodynamic characteristics of fluid flows in a spinner flask, a common stirred suspension culture vessel used in laboratories. Flow patterns and distributions of shear stresses and the Kolmogorov length scales at varying impeller speeds were obtained. Comparison of the Kolmogorov length scales and sizes of hPSC aggregates, measured in the authors’ previous experimental study, showed a strong correlation between the two. In addition to the spinner flask which generated complex and transient turbulent flows, this study investigated a newly developed rotary wall vessel that had been designed to produce laminar, circular Couette flows in order to control shear stress. CFD simulations revealed significantly more uniform and homogeneous flows compared to those in the spinner flask, suggesting that the rotary wall vessel is a suitable culture vessel to investigate roles of shear stress on hPSCs in suspension.

Stirred suspension culture is becoming a popular method for expanding human pluripotent stem cells (hPSCs). While stirring generates adequate fluid motions to lift the cells and facilitates mass transfers (of nutrients, dissolved gases, and metabolic wastes), excessive stirring could impose hydrodynamic forces deleterious for the growth of the cells. In this study, computational fluid dynamics (CFD) simulations were performed to first investigate hydrodynamic characteristics of fluid flows in a spinner flask, a common stirred suspension culture vessel used in laboratories. Flow patterns and distributions of shear stresses and the Kolmogorov length scales at varying impeller speeds were obtained. Comparison of the Kolmogorov length scales and sizes of hPSC aggregates, measured in the authors’ previous experimental study, showed a strong correlation between the two. In addition to the spinner flask which generated complex and transient turbulent flows, this study investigated a newly developed rotary wall vessel that had been designed to produce laminar, circular Couette flows in order to control shear stress. CFD simulations revealed significantly more uniform and homogeneous flows compared to those in the spinner flask, suggesting that the rotary wall vessel is a suitable culture vessel to investigate roles of shear stress on hPSCs in suspension.

Astrocytes respond to brain injury at a cellular level by the process of reactive astrogliosis, and are able to adjust their response according to the severity of the insult. Included in the reactive response is the process of phagocytosis, where astrocytes clean up surrounding cellular debris from damaged cells. In this study, we observe the process of phagocytosis by primary cortical astrocytes in the presence of media flow across the apical surface of the cells. Both static and cells under flow conditions respond consistently via phagocytosis of laser-induced cellular debris. We found that astrocytes exposed to shear flow initiate phagocytosis at a consistently faster rate than cells observed under static conditions. Shear forces created by laminar flow were analyzed as well as the flow fields created around astrocyte cells. Results suggest astrocyte phagocytosis is a mechanosensitive response, thus revealing the potential to enhance astrocyte phagocytic cleanup of damaged nervous tissue.

Microcirculatory preservation is essential for patient recovery from hemorrhagic shock. In hemorrhagic shock, microcirculatory flow and pressure are greatly reduced, creating an oxygen debt that may eventually become irreversible. During shock, tissues become hypoxic, cellular respiration turns to anaerobic metabolism, and the microcirculation rapidly begins to fail. This condition requires immediate fluid resuscitation to promote tissue reperfusion. The choice of fluid for resuscitation is whole blood; however, this may not be readily available and, on a larger scale, may be globally insufficient. Thus, extensive research on viable alternatives to blood has been undertaken in an effort to develop a clinically deployable blood substitute. This has not, as of yet, achieved fruition, in part due to an incomplete understanding of the complexities of the function of blood in the microcirculation. Hemodynamic resuscitation is acknowledged to be contingent on a number of factors other than volume expansion. The circulation of whole blood is carefully regulated to optimize oxygen delivery to the tissues via shear stress modulation through blood viscosity, inherent oxygen-carrying capacity, cell-free layer variation, and myogenic response, among other variables. Although plasma expanders can address a number of these issues, hemoglobin-based oxygen carriers (HBOCs) introduce a method of replenishing the intrinsic oxygen-carrying capacity of blood. There continue to be a number of issues related to HBOCs, but recent advances in the next-generation HBOCs show promise in the preservation of microcirculatory function and limiting toxicities. The development of HBOCs is now focused on viscosity and the degree of microvascular shear stress achieved in order to optimize vasoactive and oxygen delivery responses by leveraging the restoration and maintenance of physiological responses to blood flow in the microcirculation. Blood substitutes with higher viscous properties tend to improve oxygen delivery compared to those with lower viscosities. This review details current concepts in blood substitutes, particularly as they relate to trauma/hemorrhagic shock, with a specific focus on their complex interactions in the microcirculation.

Introduction: Atherosclerotic complications represent the leading cause of cardiovascular mortality globally. Dysfunction of endothelial cells (ECs) often initiates the pathological events in atherosclerosis. Objectives: In this study, we sought to investigate the transcriptional profile of atherosclerotic aortae, identify novel regulator in dysfunctional ECs and hence provide mechanistic insights into atherosclerotic progression. Methods: We applied single-cell RNA sequencing (scRNA-seq) on aortic cells from Western diet-fed apolipoprotein E-deficient (ApoE−/−) mice to explore the transcriptional landscape and heterogeneity of dysfunctional ECs. In vivo validation of SOX4 upregulation in ECs were performed in atherosclerotic tissues, including mouse aortic tissues, human coronary arteries, and human renal arteries. Single-cell analysis on human aortic aneurysmal tissue was also performed. Downstream vascular abnormalities induced by EC-specific SOX4 overexpression, and upstream modulators of SOX4 were revealed by biochemical assays, immunostaining, and wire myography. Effects of shear stress on endothelial SOX4 expression was investigated by in vitro hemodynamic study. Results: Among the compendium of aortic cells, mesenchymal markers in ECs were significantly enriched. Two EC subsets were subsequently distinguished, as the ‘endothelial-like’ and ‘mesenchymal-like’ subsets. Conventional assays consistently identified SOX4 as a novel atherosclerotic marker in mouse and different human arteries, additional to a cancer marker. EC-specific SOX4 overexpression promoted atherogenesis and endothelial-to-mesenchymal transition (EndoMT). Importantly, hyperlipidemia-associated cytokines and oscillatory blood flow upregulated, whereas the anti-diabetic drug metformin pharmacologically suppressed SOX4 level in ECs. Conclusion: Our study unravels SOX4 as a novel phenotypic regulator during endothelial dysfunction, which exacerbates atherogenesis. Our study also pinpoints hyperlipidemia-associated cytokines and oscillatory blood flow as endogenous SOX4 inducers, providing more therapeutic insights against atherosclerotic diseases.

In this study, we sampled the original sediment columns from three points located in the eastern, central, and western areas of Chaohu Lake, and then investigated sediment resuspension under hydraulic disturbances in the laboratory. The results showed that when the hydraulic disturbance is weak and sediment surface shear stress is small (

The study examined the strength of the universal joint after it was loaded with torsion. It used different materials that can withstand tensile stress in accordance with accepted principles and made modifications to the yoke as a result of the topology optimization process. The topology optimization determined that the yoke's part needed to withstand load without changing its dimensions and minimize stress distribution. According to the results, the maximum shear stress on the spider of the original universal joint model made of JIS-SF590A steel was 84.57 MPa, the shear stress on the yoke component was 30.84 MPa, and the maximum von Mises was 341.1 MPa. As a result of using JIS-SF590A steel, yoke modification 3 has produced a reduction in shear stress of 12.97 % and a reduction in von Mises stress of 35.33 % from the original yoke. This is the most efficient design of yoke and also this modified yoke form provides a wider elevation angle and is easier to manufacture.

This paper investigates the effect of different geometries of approach embankments and guides banks on the flow pattern and bed shear stress values in the skewed bridges in the compound channel using three-dimensional numerical modelling. First, the numerical model was evaluated based on the results of existing laboratory studies. After ensuring its proper performance, the elliptical guide bank and the three types of abutments: vertical-wall, spill-through, and wing-wall, at different skew angles are examined. Investigation of the values of maximum velocity and bed shear stress at the flow-conducting embankment and the flow-splitting embankment showed that in the flow-conducting embankment, the best performance is assigned to the elliptical guide bank. In contrast, the performance of various abutments is different for the flow-splitting embankment depending on the skew angle of the bridge. Then, different patterns based on streamlines for the geometry plan of the guide bank were proposed and studied. The results show that the most suitable pattern for the guide bank reduces the maximum flow velocity by up to 15% and reduces the maximum bed shear stress by up to 80% around the flow-splitting embankments.

Abstract Background Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. Methods Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4–6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. Results Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. Conclusions Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.

Abstract Three-dimensional (3D) bioprinting fabricates 3D functional tissues/organs by accurately depositing the bioink composed of the biological materials and living cells. Even though 3D bioprinting techniques have experienced significant advancement over the past decades, it remains challenging for 3D bioprinting to artificially fabricate functional tissues/organs with high post-printing cell viability and functionality since cells endure various types of stress during the bioprinting process. Generally, cell viability which is affected by several factors including the stress and the environmental factors, such as pH and temperature, is mainly determined by the magnitude and duration of the stress imposed on the cells with poorer cell viability under a higher stress and a longer duration condition. The maintenance of high cell viability especially for those vulnerable cells, such as stem cells which are more sensitive to multiple stresses, is a key initial step to ensure the functionality of the artificial tissues/organs. In addition, maintaining the pluripotency of the cells such as proliferation and differentiation abilities is also essential for the 3D-bioprinted tissues/organs to be similar to native tissues/organs. This review discusses various pathways triggering cell damage and the major factors affecting cell viability during different bioprinting processes, summarizes the studies on cell viabilities and functionalities in different bioprinting processes, and presents several potential approaches to protect cells from injuries to ensure high cell viability and functionality.