Effect Of Shear Stress Research Articles

Analytical method for calculation of the strength of cylindrical rock specimens during their longitudinal stress

The goal of this research is to develop a method for calculating the strength of cylindrical rock specimens under axial failure. This will allow for the management of the stress-strain state of rock masses, which is an important issue for many mining companies. To achieve this goal, analytical modeling of the process of failure of cylindrical rock specimens under axial failure was carried out. This was done using experimental values of four indicators of rock properties: shear strength, coefficients of internal and external friction, and elasticity modulus. The results of this research allow for the determination of the ultimate strength and residual strength of cylindrical rock specimens using the four property indicators. These indicators can be experimentally determined using simple methods in laboratory conditions of mining companies. The scientific novelty of this research lies in the fact that analytical modeling of the process of failure of cylindrical rock specimens under axial failure was conducted for the first time, taking into account internal and external friction. This allowed for new results to be obtained and provided a basis for the development of new methods for managing the state of rock masses. The practical significance of this research lies in the fact that the proposed method allows for the determination of the ultimate and residual strength of rock specimens using four property indicators. These indicators can be experimentally determined in mining company laboratories, making the calculation results applicable for the management of the state of rock masses and the efficient destruction of rocks during disintegration. Thus, this method has significant practical significance for the mining industry. A method for calculating the strength of cylindrical specimens under longitudinal failure mode has been developed. The average convergence of calculated strength values with fс = 0.5 to experimental data is 83.4%, which corresponds to a good level of reliability for rock materials. It has been shown that the self-organization of longitudinal failure mode in cylindrical rock specimens occurs in accordance with Coulomb's criterion of maximum effective shear stress, which has been improved to account for contact friction.

Stirred culture of cartilaginous microtissues promotes chondrogenic hypertrophy through exposure to intermittent shear stress.

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.

A Soil-Structure Interaction Study using Sustainable Structural Fill below Foundations

Structural fill is utilized to improve the bearing capacity and reduce settlement below foundations supported on weak soils or when foundations are supported on filled up soil. The present study evaluates the potential application of municipal solid waste finer fraction (MSW-FF) as a sustainable structural fill material. The finer fraction constitutes significant proportion of old landfill waste in cities, and do not easily find applications as compared to the other fraction of old waste. The present work determines the engineering properties of MSW-FF. A detailed assessment has also been carried out to evaluate the bearing capacity, settlement and modulus of subgrade reaction for the shallow foundation of different sizes and shapes resting on (a) soil with low subgrade modulus and (b) soil improved with a layer of MSW-FF as structural fill. A soil-structure interaction analysis has also been carried out by utilizing STAAD Pro. software, to understand the effect of soil and foundation stiffness on the foundation design parameters, viz., base pressure, settlement, bending moment and shear stress in shallow foundations for both cases (natural soil and with MSW-FF as structural fill). The comparison of different foundation systems resting on soil improved with MSW-FF structural fill layer and soil with low subgrade modulus has been presented to demonstrate the efficacy of MSW-FF as a suitable structural fill material. From the soil-structure interaction analysis, it is observed that the effect of soil subgrade modulus on foundation base pressure and settlement is prominent, while having a negligible effect of bending moment and shear stress in the foundation. Further, the relative stiffness of foundation and soil has a significant effect on the foundation design parameters. The study results are quite encouraging with respect to the potential of utilizing MSW-FF as a sustainable structural fill and put forward a new and promising alternate material for application in different infrastructure projects.

Simulation of LDL permeation into multilayer wall of a coronary bifurcation using WSS-dependent model: effects of hemorheology.

Atherosclerosis, due to the permeation of low-density lipoprotein (LDL) particles into the arterial wall, is one of the most common and deadly diseases in today's world. Due to its importance, numerous studies have been conducted on the factors affecting this disease. In this study, using numerical simulation, the effects of Wall Shear Stress (WSS), non-Newtonian behavior of blood, different values of hematocrit and blood pressure on LDL permeation into the arterial wall layers are investigated in a 4-layer wall model of a coronary bifurcation. To obtain the velocity and concentration fields in the fluid domain, the Navier-Stokes, Brinkman, and mass transfer equations are numerically solved in the lumen and wall layers. Results show that it is important to consider the effects of WSS on transport properties of endothelium layer in bifurcations and this leads to completely different concentration profiles compared to the constant properties model. Our computations show that a giant accumulation of LDL in the intima layer of the outer wall of the left anterior descending artery, especially in low WSS regions, may lead to atherosclerosis. It is also, necessary to consider the non-Newtonian behavior of blood in bifurcations due to its direct effect on WSS. A pressure-induced increase in the half-width of leaky junctions may be responsible for the higher risk of atherosclerosis in hypertension. In addition, it is shown that the dominant mechanism in LDL permeation into the wall is convection, and also, hypertension increases the effect of mass transfer by convection mechanism more than the diffusion mechanism. Furthermore, our results are consistent with various clinical studies.

Effects of shear stress and shear protectants on heterotrophic culture of Haematococcus pluvialis

A strategy named “Sequential Heterotrophy-Dilution-Photoinduction” is used for commercial production of astaxanthin in Haematococcus pluvialis. However, shear stress during heterotrophic culture has become the technical bottleneck for the wide application and amplification of this technology in microalgae culture, especially in the heterotrophic culture of H. pluvialis. To clarify the effects of shear stress, the influence of shear stress generated by different aeration rates on the heterotrophic growth of H. pluvialis was first investigated. The results showed that shear stress could cause the transformation of motile cells to non-motile cells, resulting in decrease in growth rate. The critical shear stress was produced by a superficial gas velocity of >3.21 × 10−3 m·s−1. The further analysis based on computational fluid dynamics indicated that shear stress-induced damage to cells was mainly caused by bubble rupture. To reduce the negative effects of shear stress, 0.05 % of Pluronic F-68 was selected for shear protection. Finally, it was successfully applied to the heterotrophic culture of H. pluvialis in a 500 L fermenter, increasing the cell yield by 30.39 %. This study could provide a reference and basis for the control of heterotrophic culture conditions and scale-up of H. pluvialis, and a feasible strategy for reducing the shear stress-induced damage during the heterotrophic process.

Effects of initial static shear stress on cyclic behaviour of sand stabilised with colloidal silica

Colloidal silica (CS) grouting is a soil improvement technique introduced as an innovative remedial measure against seismic liquefaction. It consists of injecting soils with a time-hardening, nanosilica-based solution forming a silica gel among soil particles. This paper presents the results of an experimental study on the effects of an initial static shear stress on the behaviour of a cyclically loaded clean sand stabilised with 5% CS. Undrained cyclic triaxial tests were performed to analyse the cyclic response of loose untreated and stabilised sand specimens, isotropically or anisotropically consolidated at the same initial mean effective stress. The consolidation stage was used to provide insight on the compressibility of stabilised soil. Stress–strain behaviour, pore water pressure response and cyclic shear resistance were investigated. The results showed that: (i) stabilised sand exhibits higher compressibility than the untreated one during isotropic consolidation; (ii) cyclic strength is higher for stabilised sand than for the untreated one, increasing as the degree of anisotropic initial stress increases; and (iii) extra pore water pressure development does not depend on the degree of initial anisotropy for stabilised sand, while the same does not hold for untreated sand. Simplified relationships are proposed to describe the consolidation process and the residual extra pore water pressure build-up process.

Dynamic evolution of membrane biofouling in feed channels affected by spacer–membrane clearance and the induced hydrodynamic conditions

Membrane biofouling is regarded as a Gordian knot in applying reverse osmosis and nanofiltration for water treatment. It occurs in the feed spacer channels of spiral wound membrane elements. The influence of feed spacer structure on hydrodynamic condition and biofouling development remains yet to be fully understood. This study aims to quantify the dynamic evolution and spatial distribution of biomass in feed spacer channels, and reveal the great importance of spacer–membrane clearance in the biofouling development. Four kinds of feed spacers with the same thickness (28 mil) but different clearance width, by varying filament diameter (0.4, 0.45, 0.55 and 0.6 mm), were used. A relatively long-term (20 d) biofouling experiment was conducted by using a feed solution of lower bacterial load and nutrient dosage. Results showed that the “shear stress effect” dominated the early stage of biofouling as biofilm was first attached to the low-shear regions, regardless of the spacer–membrane clearance width. In the middle and late stage, the “blocking effect” emerged with the continuous accumulation of biomass, as was especially the case in the feed channel with narrow spacer–membrane clearance. In this period, biofilm was prone to deposit and block the narrow flow passage between the spacer filaments and membrane surface, which decreased the uniformity of flow field, expanded the flow “dead zone” area, boosted the feed channel pressure (FCP) drop, and resultantly accelerated the rate of membrane biofouling. Enhancement of the “shear stress effect” under an appropriate range of spacer–membrane clearance width and thus channel porosity, as well as customed design of feed spacer geometries according to specific fouling locations are suggested for the future optimization of feed spacer.

Cell senescence alters responses of porcine trabecular meshwork cells to shear stress.

Mechanical microenvironment and cellular senescence of trabecular meshwork cells (TMCs) are suspected to play a vital role in primary open-angle glaucoma pathogenesis. However, central questions remain about the effect of shear stress on TMCs and how aging affects this process. We have investigated the effect of shear stress on the biomechanical properties and extracellular matrix regulation of normal and senescent TMCs. We found a more significant promotion of Fctin formation, a more obvious realignment of F-actin fibers, and a more remarkable increase in the stiffness of normal cells in response to the shear stress, in comparison with that of senescent cells. Further, as compared to normal cells, senescent cells show a reduced extracellular matrix turnover after shear stress stimulation, which might be attributed to the different phosphorylation levels of the extracellular signal-regulated kinase. Our results suggest that TMCs are able to sense and respond to the shear stress and cellular senescence undermines the mechanobiological response, which may lead to progressive failure of cellular TM function with age.

Mechano-regulation of Wnt/β-Catenin signaling to control paraxial versus lateral mesoderm lineage bifurcation.

Mechanical cues are involved in many biological processes, including embryonic development and patterning. For example, external mechanical forces (shear stress), lateral cell-cell interactions, and mechanical properties (stiffness and composition) of the extracellular matrix are thought to modulate Wnt signaling, which is a highly conserved pathway involved in regulating stem cell renewal, proliferation, and differentiation. In this work, we employed a customized higher-throughput shear stress induction device for the controlled application of mechanical stress to study the effects of shear stress on the differentiation of human induced pluripotent stem cells (hiPSCs) toward the three germ layers. We found that mechanical stress alters lineage commitment during ectoderm and mesoderm differentiation. We show that this effect correlates with reduced Wnt signaling, evaluated in terms of the promoter activity of an established TCF3-responsive promoter. Whole transcriptome sequencing and pathway enrichment analysis of the differentially expressed genes between hiPSC-derived mesoderm cells differentiated in the presence or absence of piston-induced shear stress confirmed that Wnt/β-catenin signaling is among the most affected developmental pathways. Furthermore, our results suggest that suitably programmed shear stress application could be used to selectively promote differentiation of hiPSCs to either lateral or paraxial mesoderm in commercially available media.

Abstract 14699: Effect of Shear Stress on Arterial Inflammation and Development of Healed Plaque: A Comprehensive Shear Stress-Molecular Imaging Study Based on a Novel Multispectral Fluorescence Lifetime Imaging Catheter

Introduction and Hypothesis: Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) in vivo in beating human coronary arteries. Methods and Results: We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaque in vivo in a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p>0.001) and a positive correlation between ESS and ch.1 lifetime (p>0.001). Conclusions: Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.

Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling

BackgroundIn brain, microvascular endothelial cells are exposed to various forces, including shear stress (SS). However, little is known about the effects of high shear stress (HSS) on human brain microvascular endothelial cells (HBMECs) and the underlying mechanism. The cholesterol efflux regulator ATP-binding cassette subfamily A member 1 (ABCA1) has been demonstrated to exert protective effect on HBMECs. However, whether ABCA1 is involved in the mechanism underneath the effect of HSS on HBMECs remains obscure. In the present study, a series of experiments were performed to better understand the effect of HSS on cellular processes of HBMECs and the possible involvement of ABCA1 and PI3K/Akt/eNOS in the underlying mechanisms.ResultsHBMECs were subjected to physiological SS (PSS) or high SS (HSS). Cell migration was evaluated using Transwell assay. Apoptotic HBMECs were detected by flow cytometry or caspase3/7 activity. IL-1β, IL-6, MCP-1 and TNF-α levels were measured by ELISA. RT-qPCR and western blotting were used for mRNA and protein expression detection, respectively. ROS and NO levels were detected using specific detection kits. Compared to PSS, HBMECs exhibited decreased cell viability and migration and increased cell apoptosis, increased levels of inflammatory cytokines, and improved ROS and NO productions after HSS treatment. Moreover, HSS downregulated ABCA1 but upregulated the cholesterol efflux-related proteins MMP9, AQP4, and CYP46 and activated PI3K/Akt/eNOS pathway. Overexpression of ABCA1 in HBMECS inhibited PI3K/Akt/eNOS pathway and counteracted the deleterious effects of HSS. Contrary effects were observed by ABCA1 silencing. Inhibiting PI3K/Akt/eNOS pathway mimicked ABCA1 effects, suggesting that ABCA1 protects HBMECs from HSS via PI3K/Akt/eNOS signaling.ConclusionThese results advanced our understanding on the mechanisms of HSS on HBMECs and potentiated ABCA1/PI3K/Akt/eNOS pathway as therapeutic target for cerebrovascular diseases.

Assessing local scour at rectangular bridge piers

The scour depth at bridge piers depends on a large number of variables. This study aims at revisiting the influence of rectangular piers' shape on local scouring. The scour around circular and rectangular bridge piers with length to width (L/D) of 1, 3, 4.5, 6, 7.5, and 9 was experimentally and numerically investigated at shallow water conditions (water depth to pier width (h/D) ratio varied from 1.4 to 2.32). Fifty-two experimental runs were carried out with a mobile bed made of non-ripples uniform sand with a median sediment grain size (d50) of 0.6 mm. The results show that L/D would influence the dimensionless scour depth (ys/D). The rectangular pier with L/D of 4.5 had the maximum ys/D and at L/D of 7.5 and 9 the ys/D was highly reduced. The Flow 3D model was used to verify the effect of downflow, shear stress, streamwise velocity and turbulence (energy and intensity) on the ys/D. The numerical results emphasized that the maximum scour would occur in terms of downflow and shear stress at L/D of 4.5. A new empirical equation (R2 = 0.904 and RMSE = 0.238) for predicting the maximum ys/D at rectangular piers was obtained. Compared with the similar formulas in the literature for predicting ys/D, accurate predictions at the rectangular pier with L/D of 1–9 were registered in this study.

Accelerated testing methods to analyse long term stability of a Phase Change Material under the combined effect of shear stress and thermal cycling

The long-term stability of a Phase Change Material (PCM) is a key point for its selection in energy storage devices. This work studies the suitability of a commercial paraffin wax in an active scraped surface heat exchanger for solar energy storage purposes. In these devices, the continuous scraping of inner walls during solidification removes PCM and increases the released heat. Hence, the PCM is affected by a high level of shear stress. In order to study a potential degradation of the paraffin, a novel accelerated procedure has been designed for obtaining samples with a different number of thermal and scraping cycles. The procedure allows to evaluate the effect of shear stresses, thermal cycles and their combined effects separately. Up to 3000 cycles have been generated, which accounts for around 8 years of continuous daily work in the heat exchanger. The measurements through Differential Scanning Calorimetry, rheometry and thermal conductivity analysis have shown that neither the thermal nor the scraping cycling have a significant impact on the paraffin thermo-physical properties. According to the findings reported in this work, paraffin wax RT44HC can be successfully used in scraped surface heat exchangers. It is expected that other commercial paraffins would be also suitable since most of them share the fact of being blends of alkanes and other hydrocarbons.

Determination of shear strength parameters of compacted high plasticity clay soils based on different laboratory tests

In civil engineering projects, soils are compacted to improve their engineering behavior and properties. Compacted soils are widely used in dams, embankments and road infrastructure. Compacted fine-grained soils, especially clay-containing soils, are frequently used as barriers to water and pollutant movement in landfills. Shear strength parameters of compacted high plasticity clay soils depend on many variables such as consistency limits, dry density, and degree of saturation. In this study, 20 high plasticity clay soil samples were used and geotechnical identification tests were performed on each of them. Direct shear box and unconfined compression tests were carried out to determine the shear strength parameters of the samples prepared by compression in their compaction characteristics. As a result of this study, the relationships between the geotechnical properties of soil samples and both the effective shear strength parameters and total shear stress parameters were evaluated.

Failure mechanism of methane drainage borehole in soft coal seams: Insights from simulation, theoretical analysis and in-borehole imaging

Methane drainage borehole in soft coal seams is prone to instability. This could seriously compromise methane drainage efficiency, leading to risks of methane hazards at coal mines. In this paper, the failure of methane drainage boreholes in soft coal seams is studied through theoretical analysis, numerical simulation and field monitoring methods, which aims to guide the borehole protection and improve the methane drainage capacity. The functional relationship between effective radial normal stress and effective tangential shear stress at the unstable position of the borehole and the in-situ stress and pore pressure is constructed through the theoretical study. The equation to derive borehole wall collapse pressure is established, considering cohesion, internal friction angle, coal seam porosity, pore pressure, in-situ stress and other factors. The numerical modelling shows that the coal around the borehole undergoes tensile breakage towards the borehole in both single and multiple borehole conditions. The vertical displacement at the borehole top is the largest and the borehole turned into an elliptical shape under compression. Also, it shows the opening and the end of the borehole are at higher failure risks than middle sections. The horizontal and vertical displacements of multiple boreholes are larger than that of a single borehole. While the usage of multiple boreholes improves the methane drainage efficiency, it brings more challenges to the borehole stability. The creep deformation law of borehole is revealed based on new developed in-borehole imaging monitoring system, including four stages: first (transient), second (steady-state), tertiary (accelerating state) and closure. The field measurement shows that the methane drainage efficiency was relatively high in the first two stages, and then the efficiency dropped rapidly when borehole closing. The research results are critical for guiding methane drainage borehole protection, improving the methane drainage efficiency and enhancing safety in production.

Resuspension of trace explosive particle residues by planar impinging jet: Effects of exposure duration and wall shear stress

Aerodynamic particle resuspension is important in many practical applications, such as surface cleaning, understanding particle fate in the environment, and surface sampling. In practical application, the probability of particle resuspension from the surface depends on several parameters, such as particle size, morphology, chemical composition, surface properties, environmental and flow conditions. The wall shear stress (τw) links fluid motion and forces acting on the particle and can be used to characterize particle resuspension. The literature reports that the resuspension rates decay as 1/t at long exposure times; however, the effect of very short exposures to aerodynamic forces on the resuspension of irregular microparticles has not been characterized. This work examines the effect of τw and exposure duration utilizing planar jet pulses. We evaluated resuspension silica spheres and irregular Trimethylenetrinitramine (RDX) microparticles from a smooth glass surface with a 10–100 ms pulse duration and extended exposure (60 s) for the same wall shear stresses. Reducing the jet duration shows that the removal rate is inversely proportional to exposure time; the trend is more visible at lower τw. At higher shear stresses, up to 80% of particles are removed in the first 10 ms of exposure to aerodynamic force.

Notch signaling and fluid shear stress in regulating osteogenic differentiation.

Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, a locked nucleic acid (LNA)/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation.

Influence of sloping ground conditions on cyclic liquefaction behavior of sand under simple shear loading

An experimental program of undrained cyclic simple shear tests was undertaken on Ticino sand, covering a broad range of initial relative densities and static stress levels, to investigate the effect of an initial static shear stress on failure mechanism, cyclic resistance, and pore water pressure generation. The results indicated that two types of failure mechanisms occurred, namely cyclic mobility and plastic strain accumulation, depending on the magnitude of the initial static shear stress with respect to the applied cyclic shear stress. Test results showed that the cyclic resistance of Ticino sand may either increase or decrease with an increasing initial static shear stress depending on the density state of the sand. The Kα correction factors measured under cyclic simple shear loading were compared with the values reported in the literature based on both cyclic triaxial and simple shear tests, suggesting that Kα could be dependent on the particle gradations and grain shape for a given depositional mechanism. Finally, it was verified that the initial static shear stress has a remarkable impact on the development of cyclic pore-water pressures (PWP) of the sands so that a modified PWP generation model has been effectively proposed in the present study.

Influence of Shear Stress, Inflammation and BRD4 Inhibition on Human Endothelial Cells: A Holistic Proteomic Approach.

Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome.

A novel ceRNA regulatory network involving the long noncoding NEAT1, miRNA-466f-3p and its mRNA target in osteoblast autophagy and osteoporosis.

Osteoporosis (OP) is a systemic metabolic disorder characterized by a reduction in bone tissue volume. LncRNAs have been reported to act as regulators of several human diseases. Specifically, lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in proliferation, differentiation and apoptosis in osteoclasts and bone marrow mesenchymal stem cells and regulates the occurrence and development of OP. However, the relationship between NEAT1 and osteoblast autophagy and its mechanism are still unclear. Western blotting of LC3 and P62 was used to evaluate the effect of fluid shear stress (FSS) on autophagy in MC3T3-E1 osteoblasts. Total transcriptome sequencing and bioinformatics analyses were performed on osteoblasts loaded with and without FSS. qPCR was performed to examine the expression of NEAT1 in OP bone tissues and osteoblasts. The RNA-FISH was performed to study the localization of lncRNA NEAT1 and miR-466f-3p in MC3T3-E1 osteoblasts. In vitro, western blotting, transmission electron microscopy (TEM), immunofluorescence (IF) staining and qPCR were performed to verify the biological functions of NEAT1, miR-466f-3p and HK2. Subsequently, we conducted bioinformatics analysis and dual luciferase reporter assays to identify the relationships among NEAT1, miR-466f-3p and HK2. Additionally, rescue assays were conducted on osteoblasts to clarify the regulatory network of the NEAT1/miR-466f-3p/HK2 signalling pathway. In vivo, the OVX mouse model was used to investigate the effects of si-NEAT1 on autophagy in OP mice. The distal femur and serum were collected for further micro-CT analysis, blood biochemistry, and haematoxylin-eosin and Alizarin red staining (ARS). Immunohistochemistry (IHC) was performed to assess the protein expression of LC3 and HK2. NEAT1 expression was upregulated in OP tissues and osteoblast lines exposed to FSS. Knockdown of NEAT1 inhibited autophagy in vitro and in vivo. Further studies demonstrated that NEAT1 positively regulated HK2 expression via its competing endogenous RNA effects on miR-466f-3p. Moreover, we found the NEAT1/miR-466f-3p/HK2 axis regulated autophagy in osteoblasts. Knocking down NEAT1 inhibited autophagy in osteoblasts via the miR-466f-3p/HK2 signalling pathway, which may provide new ideas for novel molecular therapeutic targets of postmenopausal OP. KEY MESSAGES: • Fluid shear stress (FSS) can promote autophagy of osteoblast and performed transcriptome sequencing. • NEAT1 is overexpressed in osteoporosis and could regulate osteoblast cells autophagy. • Knockdown of lncRNA NEAT1 inhibited osteoblast cells autophagy by sponging miRNA-466f-3p and targeting HK2 in osteoporosis.