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To reveal the mechanism of shear failure of en-echelon joints under cyclic loading, such as during earthquakes, we conducted a series of cyclic shear tests of en-echelon joints under constant normal stiffness (CNS) conditions. We analyzed the evolution of shear stress, normal stress, stress path, dilatancy characteristics, and friction coefficient and revealed the failure mechanisms of en-echelon joints at different angles. The results show that the cyclic shear behavior of the en-echelon joints is closely related to the joint angle, with the shear strength at a positive angle exceeding that at a negative angle during shear cycles. As the number of cycles increases, the shear strength decreases rapidly, and the difference between the varying angles gradually decreases. Dilation occurs in the early shear cycles (1 and 2), while contraction is the main feature in later cycles (3−10). The friction coefficient decreases with the number of cycles and exhibits a more significant sensitivity to joint angles than shear cycles. The joint angle determines the asperities on the rupture surfaces and the block size, and thus determines the subsequent shear failure mode (block crushing and asperity degradation). At positive angles, block size is more greater and asperities on the rupture surface are smaller than at nonpositive angles. Therefore, the cyclic shear behavior is controlled by block crushing at positive angles and asperity degradation at negative angles.

In vitro models of kidneys have limited effectiveness owing to the complex structure and functions of the kidney when compared with other organs. Therefore many renal function evaluations are currently being carried out through animal experiments. In contrast, efforts are being made to apply biomimetic systems, such as organ-on-a-chip, which is based on microfluidic device technology, to serve as an in vitro model for the kidney. These systems aimed to recreate a physiological cultivation environment. This review has provided an overview of organ-on-a-chip research focused on glomeruli and tubules as in vitro models for the kidney and discusses future prospects.

This work presents a theoretical analysis of the non-linear behavior of blood flow along an angled arterial section with overlapping stenosis. An elastic cylindrical tube with a moving wall is used to represent the artery, and a Casson liquid is used to simulate blood flowing through it. The nonlinear equations that govern blood flow are taken into account. The influence of the pulsatile pressure gradient caused by the regular heartbeat on the flow process in the stenosed artery is demonstrated mathematically. The current analytical method can compute the wall shear stress, flow resistivity, and velocity profiles with mild stenosis assumption by applying the boundary conditions. Numerical calculations of the desired quantities are carried out systematically. They provide an overview of how the degree of stenosis and the malleability of the artery wall influence blood flow abnormalities. Concerning the height of stenosis, the surface shear stress and the resistivity to flow increase together with an increase in the proclivity angle.

The efficacy of a sanitizer in biofilm removal may be influenced by a combination of factors such as sanitizer exposure time and concentration, bacterial species, surface topography, and shear stresses. We employed an inline biofilm reactor to investigate the interactions of these variables on biofilm removal with chlorine. The CDC bioreactor was used to grow E. coli O157:H7 and L. monocytogenes biofilms as a single species or with Ralstonia insidiosa as a dual-species biofilm on stainless steel, PTFE, and EPDM coupons at shear stresses 0.368 and 2.462 N/m2 for 48 hours. Coupons were retrieved from a CDC bioreactor and placed in an inline biofilm reactor and 100, 200, or 500 ppm of chlorine was supplied for 1- and 4 min. Bacterial populations in the biofilms were quantified pre- and posttreatment by plating on selective media. After chlorine treatment, reduction (Log CFU/cm2) in pathogen populations obtained from three replicates was analyzed for statistical significance. A 1-min chlorine treatment (500 ppm), on dual-species E. coli O157:H7 biofilms grown at high shear stress of 2.462 N/m2 resulted in significant E. coli O157:H7 reductions on SS 316L (2.79 log CFU/cm2) and PTFE (1.76 log CFU/cm2). Similar trend was also observed for biofilm removal after a 4-min chlorine treatment. Single species E. coli O157:H7 biofilms exhibited higher resistance to chlorine when biofilms were developed at high shear stress. The effect of chlorine in L. monocytogenes removal from dual-species biofilms was dependent primarily on the shear stress at which they were formed rather than the surface topography of materials. Besides surface topography, shear stresses at which biofilms were formed also influenced the effect of sanitizer. The removal of E. coli O157:H7 biofilms from EPDM material may require critical interventions due to difficulty in removing this pathogen. The inline biofilm reactor is a novel tool to evaluate the efficacy of a sanitizer in bacterial biofilm removal.

The ex vivo production of platelets from induced pluripotent cells (iPSCs) may offer a safer and sustainable alternative for transfusions and drug delivery systems (DDS). However, the mass production of the clinically required number of iPSC-derived platelets (iPSC-PLTs) is challenging. Here, we introduce recent technologies for mass production and the first-in-human clinical trial using ex vivo iPSC-PLTs. To this end, we established immortalized megakaryocyte progenitor cell lines (imMKCLs) as an expandable master cell bank (MCB) through the overexpression of c-MYC, BMI1 and BCL-XL, which modulated megakaryopoiesis and thrombopoiesis. We also optimized a culture cocktail for maturation of the imMKCLs by mixing an aryl hydrocarbon receptor (AhR) antagonist, SR1/GNF-316; a Rho-associated protein kinase (ROCK) inhibitor, Y-27632/Y-39983; and a small-molecule compound replacing recombinant thrombopoietin (TPO), TA-316. Finally, we discovered the importance of turbulence on the manufacturing of intact iPSC-PLTs, allowing us to develop a turbulence-based bioreactor, VerMES. Combination of the MCB and VerMES enabled us to produce more than 100 billion iPSC-PLTs, leading to the first-in-human clinical trial. Despite these advancements, many challenges remain before expanding the clinical implementation of this strategy.

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

During vascular development, endothelial cells (ECs) undergo arterialization in response to genetic programs and shear stress-triggered mechanotransduction, forming a stable vasculature. Although the Notch receptor is known to sense shear stress and promote EC arterialization, its downstream mechanisms remain unclear. In this study, the Notch downstream miR-342-5p was found to respond to shear stress and promote EC arterialization. Shear stress upregulated miR-342-5p in a Notch-dependent manner in human umbilical vein endothelial cells (HUVECs). miR-342-5p overexpression upregulated the shear stress-associated transcriptomic signature. Moreover, miR-342-5p upregulated arterial markers and promoted EC arterialization in a Matrigel plug assay and retinal angiogenesis model. In contrast, miR-342-5p knockdown downregulated arterial markers, compromised retinal arterialization, and partially abrogated shear stress and Notch activation-induced arterial marker upregulation. Mechanistically, miR-342-5p overexpression suppressed MYC to repress EC proliferation and promote arterialization, achieved by promoting MYC protein degradation by targeting the EYA3. Consistently, EYA3 overexpression rescued miR-342-5p-mediated MYC downregulation and EC arterialization. In vivo, miR-342-5p expression was notably decreased in the ligated artery in a hindlimb ischemia model, and an intramuscular injection of miR-342-5p promoted EC arterialization and improved perfusion. In summary, miR-342-5p, a mechano-miR, mediates the effects of shear stress-activated Notch on EC arterialization and is a potential therapeutic target for ischemic diseases.

This article presents the stresses at the center of a Brazilian disk (BD) for transversely isotropic rocks. It is shown that the solution of stresses at the center of an anisotropic disk is a function of the disk radius and the magnitude of applied load, as well as the material orientation with respect to the load axis and two dimensionless ratios with specific physical meanings and limitations. These two dimensionless parameters are the ratios of Young’s modulus and apparent shear modulus, although the ratio of apparent shear modulus will be eliminated if the Saint-Venant assumption is considered. Considerable finite element simulations are carried out to find the stresses at the disk center concerning the material orientation and the two dimensionless parameters. Also, an approximate formula obtained from analytical results, previously proposed in the literature for solving the tensile and compressive stresses at the disk center, is re-written and simplified based on these new definitions. The results of the approximate formula fitted to the analytical results are compared to those obtained from numerical solutions, suggesting a good agreement between the numerical and analytical methods. An approximate equation for the shear stress at the disk center is also formulated based on the numerical results. Finally, the influence of the assumptions for simplification of the proposed formula for the tensile, compressive, and shear stresses at the disk center is discussed, and simple and practical equations are proposed as estimations for the stresses at the center of the BD specimen for low to moderate anisotropic rocks. For highly anisotropic rocks, the reference plots can be used for more accuracy.

A Switched Reluctance Motor is designed for an electric auto rickshaw operating at 25 kmph. Different stator-rotor teeth combinations are worked out and the suitable combination for the application is chosen. As the application demands higher operating speeds (up to 9500 rpm), windage loss tends to hamper the machine's efficiency at these speeds. One parameter that affects the windage loss is the drag force. The drag force contributed by the rotor can be varied by changing the profile of the rotor slot. Hence, certain structural variations in the rotor slot are carried out and Computational Fluid Dynamics (CFD) is used to estimate the windage loss of each rotor slot profile. The rotor structure providing minimal windage loss is chosen for fabrication. Testing is performed on the fabricated motor and the results are compared.

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: 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.

Calcified aortic valve disease (CAVD) is a common cardiovascular disease in elderly individuals. Although it was previously considered a degenerative disease, it is, in fact, a progressive disease involving multiple mechanisms. Aortic valve endothelial cells, which cover the outermost layer of the aortic valve and are directly exposed to various pathogenic factors, play a significant role in the onset and progression of CAVD. Hemodynamic changes can directly damage the structure and function of valvular endothelial cells (VECs). This leads to inflammatory infiltration and oxidative stress, which promote the progression of CAVD. VECs can regulate the pathological differentiation of valvular interstitial cells (VICs) through NO and thus affect the process of CAVD. Under the influence of pathological factors, VECs can also be transformed into VICs through EndMT, and then the pathological differentiation of VICs eventually leads to the formation of calcification. This review discusses the role of VECs, especially the role of oxidative stress in VECs, in the process of aortic valve calcification.

In this article, the semi-analytical technique of the Hybrid Analytical and Numerical Method (the HAN Method) is used to study the non-transient forced non-Newtonian MHD Reiner-Rivlin viscoelastic fluid motion that is constrained between two plates. The magnetic field is also present in this model. The governing equations are in the PDE form and by using the Von Kármán similarity variables, they transformed into a set of ODEs. The HAN-method is applied to solve the ODEs and their associated boundary conditions, analytically. In addition, for the validation, the HAN solution results were compared with the HPM and numerical technique of Runge-Kutta results. And finally, new results were extracted from the HAN solutions in a quantitative form.

The loss of endothelial cells is associated with the accumulation of monocytes/macrophages underneath the surface of the arteries, where cells are prone to mechanical stimulation, such as shear stress. However, the impact of mechanical stimuli on monocytic cells remains unclear. To assess whether mechanical stress affects monocytic cell function, we examined the expression of inflammatory molecules and surface proteins, whose levels changed following shear stress in human THP-1 cells. Shear stress increased the inflammatory chemokine CCL2, which enhanced the migration of monocytic cells and tumor necrosis factor (TNF)-α and interleukin (IL)− 1β at transcriptional and protein levels. We identified that the surface levels of heat shock protein 70 (HSP70), HSP90, and HSP105 increased using mass spectrometry-based proteomics, which was confirmed by western blot analysis, flow cytometry, and immunofluorescence. Treatment with HSP70/HSP105 and HSP90 inhibitors suppressed the expression and secretion of CCL2 and monocytic cell migration, suggesting an association between HSPs and inflammatory responses. We also demonstrated the coexistence and colocalization of increased HSP90 immunoreactivity and CD68 positive cells in atherosclerotic plaques of ApoE deficient mice fed a high-fat diet and human femoral artery endarterectomy specimens. These results suggest that monocytes/macrophages affected by shear stress polarize to a pro-inflammatory phenotype and increase surface protein levels involved in inflammatory responses. The regulation of the abovementioned HSPs upregulated on the monocytes/macrophages surface may serve as a novel therapeutic target for inflammation due to shear stress.

At present, alloys are affected by various stress states during their deformation process. Various stresses can facilitate alloy deformation at the same time, and the influence of these stresses on material deformation is difficult to clarify. It is essential to clarify the difference in the deformation mechanism of an alloy in a single stress state In this work, the internal deformation mechanism of the Mg-13Gd-4Y–2Zn-0.5Zr alloy under two stress states at different deformation temperatures was studied by compression and torsion experiments. The results show that the grain is slightly deformed under shear stress deformation, and the long period stacking ordered (LPSO) phases of different forms show smaller kink angles, fewer kink times, and larger relative width ratios of the kink bands. Under compressive stress deformation, the grain is obviously compressed along the CD direction and presents a streamline, and the LPSO phase is severely kinked. Different stress states have a great influence on dislocation slip, and the shear stress state can easily provoke the initiation of non-basal slip. Non-basal slip has difficulty starting under compressive stress, which leads to dislocation packing. The dynamic recrystallization (DRX) fraction of compressive stress deformation is higher than that of shear stress deformation. Shear and compressive stress deformation alloys activate different kinds of twinning. In shear stress deformed alloys, tensile twins usually occur in grains with a small basal slip Schmid factor (SF). However, compression twins are activated in the compressive stress deformation alloy and occur in grains with larger SF values. When the slip is not fully coordinated with the deformation, kinking and twining occur to coordinate the deformation.

Different blood flow patterns in the arteries can alter the adaptive phenotype of vascular endothelial cells (ECs), thereby affecting the functions of ECs and are directly associated with the occurrence of lesions in the early stages of atherosclerosis (AS). Atherosclerotic plaques are commonly found at curved or bifurcated arteries, where the blood flow pattern is dominated by oscillating shear stress (OSS). OSS can induce ECs to transform into pro-inflammatory phenotypes, increase cellular inflammation, oxidative stress response, mitochondrial dysfunction, metabolic abnormalities and endothelial permeability, thereby promoting the progression of AS. On the other hand, the straight artery has a stable laminar shear stress (LSS), which promotes the transformation of ECs into an anti-inflammatory phenotype, improves endothelial cell function, thereby inhibits atherosclerotic progression. ECs have the ability to actively sense, integrate, and convert mechanical stimuli by shear stress into biochemical signals that further induces intracellular changes (such as the opening and closing of ion channels, activation and transcription of signaling pathways). Here we not only outline the relationship between functions of vascular ECs and different forms of fluid shear stress in AS, but also aim to provide new solutions for potential atherosclerotic therapies targeting intracellular mechanical transductions.

Sonothrombolysis is a technique that employs the ultrasound waves to break down the clot. Recent studies have demonstrated significant improvement in the treatment efficacy when combining two ultrasound waves of different frequencies. Nevertheless, the findings remain conflicted on the ideal frequency pairing that leads to an optimal treatment outcome. Existing experimental studies are constrained by the limited range of frequencies that can be investigated, while numerical studies are typically confined to spherical microbubble dynamics, thereby restricting the scope of the analysis. To overcome this, the present study investigated the microbubble dynamics caused by the different combinations of ultrasound frequencies. This was carried out using computational modelling as it enables the visualisation of the microbubble behaviour, which is difficult in experimental studies due to the opacity of blood. The results showed that the pairings of two ultrasound waves with low frequencies generally produced stronger cavitation and higher flow-induced shear stress on the clot surface. However, one should avoid the frequency pairings that are integer multipliers of each other, i.e., frequency ratio of 1/3, 1/2 and 2, as they led to resultant wave with low pressure amplitude that weakened the cavitation. At 0.5 + 0.85 MHz, the microbubble caused the highest shear stress of 60.5 kPa, due to its large translational distance towards the clot. Although the pressure threshold for inertial cavitation was reduced using dual-frequency ultrasound, the impact of the high-speed jet can only be realised when the microbubble travelled close to the clot. The results obtained from the present study provide groundwork for deeper understanding on the microbubble dynamics during dual-frequency sonothrombolysis, which is of paramount importance for its optimisations and the subsequent clinical translation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid-structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (-34.9%/-34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control). This fluid-structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A sedentary lifestyle, low levels of physical activity and fitness, poor dietary patterns, and psychosocial stress are strongly associated with increased morbidity and mortality from atherosclerotic cardiovascular disease (ASCVD). Conversely, engaging in regular physical activity, maintaining optimal fitness levels, adhering to a heart-healthy dietary pattern, effectively managing body weight, ensuring adequate sleep, implementing stress-reduction strategies, and addressing psychosocial risk factors are associated with a reduced risk of ASCVD. This comprehensive review synthesizes current evidence from large observational studies and randomized controlled trials on lifestyle factors as determinants of ASCVD health. It also briefly reviews mechanistic insights into how factors such as low shear stress, increased reactive oxygen species production, chronic inflammation, platelets and coagulation activation, endothelial dysfunction, and sympathetic hyperactivity contribute to the initiation and exacerbation of ASCVD risk factors. These include obesity, hyperglycemia, type 2 diabetes, hypertension, and dyslipidemia, subsequently leading to the development and progression of atherosclerosis, ultimately resulting in chronic ASCVD or acute cardiovascular events. To bridge the translational gap between epidemiologic and trial-based evidence and clinical practice, practical recommendations are summarized to facilitate the translation of scientific knowledge into actionable interventions to promote ASCVD health. Acknowledged is the gap between the evidence-based knowledge and adoption within healthcare systems, which remains a crucial objective in advancing cardiovascular health at the population level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein denaturation and aggregation resulting from the effects of interfacial stress, often enhanced by flow and shear stress, pose significant challenges in the production of therapeutic proteins and monoclonal antibodies. The influence of flow on protein stability is closely intertwined with interfacial effects. In this study, we have developed a microfluidic device capable of exposing low volume (< 320 µL) protein solutions to highly uniform shear. To disentangle the synergistic impact of flow and interfaces on protein aggregation, we fabricated two devices composed of different materials, namely poly(methyl methacrylate) (PMMA) and stainless steel. Upon application of shear, we observed formation of protein particles in the micron-size range. Notably, The number of particles generated in the steel devices was ∼ 3.5 fold lower than in the PMMA device, hinting at an interface-mediated effect. With increasing the protein concentration from 1 to 50 mg/mL we observed a saturation in the amount of aggregates, further confirming the key role of solid-liquid interfaces in inducing particle formation. Introduction of non-ionic surfactants prevented protein aggregation, even at the highest tested protein concentration and low surfactant concentrations of 0.05 mg/mL. Overall, our findings corroborate the synergistic impact of shear and interface effects on protein aggregation. The device developed in this study offers a small-scale platform for assessing the stability of antibody formulations throughout various stages of the development and manufacturing process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The efficacy of a sanitizer in biofilm removal may be influenced by a combination of factors such as sanitizer exposure time and concentration, bacterial species, surface topography, and shear stresses. We employed an inline biofilm reactor to investigate the interactions of these variables on biofilm removal with chlorine. The CDC bioreactor was used to grow E. coli O157:H7 and L. monocytogenes biofilms as a single species or with Ralstonia insidiosa as a dual-species biofilm on stainless steel, PTFE, and EPDM coupons at shear stresses 0.368 and 2.462 N/m 2 for 48 hours. Coupons were retrieved from a CDC bioreactor and placed in an inline biofilm reactor and 100, 200, or 500 ppm of chlorine was supplied for 1- and 4 min. Bacterial populations in the biofilms were quantified pre- and posttreatment by plating on selective media. After chlorine treatment, reduction (Log CFU/cm 2 ) in pathogen populations obtained from three replicates was analyzed for statistical significance. A 1-min chlorine treatment (500 ppm), on dual-species E. coli O157:H7 biofilms grown at high shear stress of 2.462 N/m 2 resulted in significant E. coli O157:H7 reductions on SS 316L (2.79 log CFU/cm 2 ) and PTFE (1.76 log CFU/cm 2 ). Similar trend was also observed for biofilm removal after a 4-min chlorine treatment. Single species E. coli O157:H7 biofilms exhibited higher resistance to chlorine when biofilms were developed at high shear stress. The effect of chlorine in L. monocytogenes removal from dual-species biofilms was dependent primarily on the shear stress at which they were formed rather than the surface topography of materials. Besides surface topography, shear stresses at which biofilms were formed also influenced the effect of sanitizer. The removal of E. coli O157:H7 biofilms from EPDM material may require critical interventions due to difficulty in removing this pathogen. The inline biofilm reactor is a novel tool to evaluate the efficacy of a sanitizer in bacterial biofilm removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Computational fluid dynamics (CFD) simulations, in-vitro setups, and experimental ex-vivo approaches have been applied to numerous alveolar geometries over the past years. They aimed to study and examine airflow patterns, particle transport, particle propagation depth, particle residence times, and particle-alveolar wall deposition fractions. These studies are imperative to both pharmaceutical and toxicological studies, especially nowadays with the escalation of the menacing COVID-19 virus. However, most of these studies ignored the surfactant layer that covers the alveoli and the effect of the air-surfactant surface tension on flow dynamics and air-alveolar surface mechanics. Methods: The present study employs a realistic human breathing profile of 4.75s for one complete breathing cycle to emphasize the importance of the surfactant layer by numerically comparing airflow phenomena between a surfactant-enriched and surfactant-deficient model. The acinar model exhibits physiologically accurate alveolar and duct dimensions extending from lung generations 18 to 23. Airflow patterns in the surfactant-enriched model support previous findings that the recirculation of the flow is affected by its propagation depth. Proximal lung generations experience dominant recirculating flow while farther generations in the distal alveolar region exhibit dominant radial flows. In the surfactant-enriched model, surface tension values alternate during inhalation and exhalation, with values increasing to 25 mN/m at the inhalation and decreasing to 1 mN/m at the end of the exhalation. In the surfactant-deficient model, only water coats the alveolar walls with a high surface tension value of 70 mN/m. Results: Results showed that surfactant deficiency in the alveoli adversely alters airflow behavior and generates unsteady chaotic breathing through the production of vorticities, accompanied by higher vorticity magnitudes (100% increase at the end of exhalation) and higher velocity magnitudes (8.69% increase during inhalation and 11.9% increase during exhalation). In addition, high air-water surface tension in the surfactant-deficient case was found to induce higher shear stress values (by around a factor of 10) on the alveolar walls than that of the surfactant-enriched case. Conclusion: Overall, it was concluded that the presence of the surfactant improves respiratory mechanics and allows for smooth breathing and normal respiration.

Many studies have shown that microbubble cavitation is one mechanism for vascular injury under ultrasonic excitation. Previous work has attributed vascular damage to vessel expansions and invaginations due to the expansion and contraction of microbubbles. However, the mechanisms of vascular damage are not fully understood. In this paper, we investigate, theoretically and experimentally, the vessel injury due to stress induced by ultrasound-induced cavitation (UIC). A bubble-fluid-vessel coupling model is constructed to investigate the interactions of the coupling system. The dynamics process of vessel damage due to UIC is theoretically simulated with a finite element method, and a focused ultrasound (FU) setup is carried out and used to assess the vessel damage. The results show that shear stress contributes to vessel injury by cell detachment while normal stress mainly causes distention injury. Similar changes in cell detachment in a vessel over time can be observed with the experimental setup. The severity of vascular injury is correlated to acoustic parameters, bubble-wall distance, and microbubble sizes, and the duration of insonation..

The connections made for steel beams are used quite often, in which a part of the beam cross-section needs to be cut at the connection joint. There are many shapes in which the location of the cutting part of the web is formed, but this is done in a manner where previous studies or calculations have not been made and may cause an adverse effect on the section's resistance to stresses. For this reason, a finite element (FE) analysis was conducted on 34 models in this research, among which many variables and notched shapes were selected that could be implemented in the web cutting process. Some specimens were first compared that were used for studying in the experiments of the previous research. Great agreement and high accuracy were obtained in the use of FE numerical analysis in the modeling of this type of steel structural elements. The maximum load capacity, the distribution of normal stresses as well as the shear stresses at the notched zone were measured. From the study of the different variables, it was observed that the use of a quarter-circle notch was the best shape for locating the beam web cutting, as the increase of the load ratio reached 1.14 when compared to the right angle. The use of a half-circle notch, either from one or both sides of the beam web, negatively affects the web's resistance to stress. A quarter-circle notched from both sides must also be used to increase the load capacity if the flange is cut from both sides.

In Malaysia, solid depositions of paraffin wax in the inner walls of production and transportation pipelines, and on the surface of production equipment have been identified as the utmost challenge in production and transportation of crude oil. In order to overcome the wax deposition issue, physical characterization of crude oil is crucial. In this study, the performance of wax inhibitor and nanoparticle, sodium cloisite Na+ is evaluated to determine their effects on the viscosity of crude oil using Brookfield DV-III viscometer. Nanoparticle was used along with 500, 800, 1000, 2000 and 5000 ppm of Poly (ethylene-co-vinyl acetate) (EVA) and Poly (maleic anhydride-alt-1-octadecene) (MA). Nanoparticle alone was able to lower the viscosity of crude oil to about 92.5%. EVA and MA were able to reduce the viscosity up to 88% and 86.4%, respectively while EVA and MA added to nanoparticle was able to reduce the viscosity up to about 94% and 89.2%. The blend between wax inhibitor and nanoparticle provides significant reduction in viscosity of crude oil.

Background/purpose: Significant research has proposed that the implant with microthread in the neck can significantly reduce marginal bone loss, but whether it is consistent in the condition of marginal bone loss is still unknown. The objective of this study is to investigate the effect of microthread on stress distribution in peri-implant bone with different bone level using finite element analysis. Materials and methods: A series of computational models of mandible segments with different bone resorption and implant models with or without microthread in the neck was installed by computer-aided design software. The simulated occlusal force of 150N was applied buccolingually on the top center point of implant. The FEA was performed, and the von Mises stress, principal stress and shear stress in peri-implant bone were recorded and analyzed. Results: In all models, the T-neck group exhibits higher von Mises stress and principal stress, as well as lower shear stress than S-neck group. Three types of stresses increase with the depth of bone resorption developed, but the differences of shear stress between two groups of implants were gradually decreased. Conclusion: The micro-thread design in implant neck can reduce marginal bone loss by decreasing shear stress in peri-implant bone, but this effect is gradually weakened with the decline of the marginal bone level.

One of the key issues involved in successfully achieving hydroxyapatite (HA) ceramic body without defects using colloidal processing technique, is the preparation of homogeneously high solid loading HA ceramic suspension. This could be achieved via controlling the HA powder properties. The maximum achievable solid loading suspension from the as received HA powder was found to be 14 vol%. The treatment of the as received powder via heat treatment process play a very versatile role in changing the physical properties of the powder. Owing to these changes, well dispersed high solid loading HA suspensions reaching 57 and 59 vol% were successfully prepared from HA powder heat-treated at 1000 and 1100 °C, respectively. The suspensions prepared from the heat-treated powder was found to have acceptable rheological properties for casting processes in terms of low particle interaction, lower number of floc and floc network and higher fluidity.

The purpose of this paper is to evaluate the exact solution of the unsteady flow of a generalized Brinkman type fluid under the effect of MHD in a channel. The classical Brinkman model reduced to non-dimensional form by using appropriate dimensionless variables. Furthermore, the non-dimensional Brinkman model is transformed to a generalize Brinkman model with Caputo-Fabrizio fractional derivative. The dimensionless Brinkman model has been solved with applicable conditions by integral transforms techniques that is Fourier and Laplace. The effect of different physical parameters and fractional order on fluid velocity and shear stress are illustrated graphically. Moreover, through this recent work, the recovery of classical Brinkman type fluid is possible through graphs.

Abstract Background Hemostatic clots have a P‐selectin positive platelet core covered with a shell of P‐selectin negative platelets. Objective To develop a new human blood microfluidic assay to interrogate core/shell mechanics. Methods A 2‐stage assay perfused whole blood over collagen/± tissue factor (TF) for 180 seconds at 100 s−1 wall shear rate, followed by buffer perfusion at either 100 s−1 (venous) or 1000 s−1 (arterial). This microfluidic assay used an extended channel height (120 µm), allowing buffer perfusion well before occlusion. Results Clot growth on collagen stopped immediately with buffer exchange, revealing ~10% reduction in platelet fluorescence intensity (at 100 s−1) and ~30% (at 1000 s−1) by 1200 seconds. Thrombin generation (on collagen/TF) reduced erosion at either buffer flow rate. P‐selectin–positive platelets were stable (no erosion) against 1000 s−1, in contrast to P‐selectin negative platelets. Thrombin inhibition (with D‐Phe‐Pro‐Arg‐CMK) reduced the number of P‐selectin‐positive platelets and lowered thrombus stability through the reduction of P‐selectin–positive platelets. Interestingly, fibrin inhibition (with H‐Gly‐Pro‐Arg‐Pro‐OH acetate salt) increased the number of P‐selectin–positive platelets but did not lower stability, suggesting that fibrin was only in the core region. Thromboxane inhibition reduced P‐selectin–positive platelets and caused a nearly 60% reduction of the clot at arterial buffer flow. P2Y1 antagonism reduced clot size and the number of P‐selectin–positive platelets and reduced the stability of P‐selectin–negative platelets. Conclusion The 2‐stage assay (extended channel height plus buffer exchange) interrogated platelet stability using human blood. Under all conditions, P‐selectin–positive platelets never left the clot.

In this study, the effects of incorporating of SiO2 nanoparticles into the ethylene glycol on the viscosity were examined. Many samples were prepared by two-step method to investigate the effects of temperature (5–65 ℃), mass fraction (0.005−5 wt.%), shear rate (3–110 1s) and sonication time (15−60 min) on viscosity. Rheological analysis revealed that despite the EG Newtonian behavior, it was found that SiO2/EG conforms to the non-Newtonian shear-thinning model. However, as the shear rate raised, the behavior tends to Newtonian. For all samples, the viscosity of SiO2/EG was higher than EG viscosity. At higher temperature as well as mass fraction and the lowest shear rate, the maximum intensification in viscosity was reported to be 133.7%. The sonication energy diminishes clustering length and consequently reduces the viscosity. It was found that the increase in sonication time from 15 min to 60 min, diminished the viscosity up to 14%.

Stenosis due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans.

Objective: The arteriovenous fistula (AVF) is the preferred method of dialysis access because of its proven superior long-term outcomes. However, women have lower rates of AVF patency and utilization than men. We used a novel mouse AVF model that recapitulates human AVF maturation to determine whether there are differences in AVF patency in female and male mice. Methods: Aortocaval fistulas were created in female and male C57BL/6 mice (9-10 weeks). At days 0, 3, 7, and 21, infrarenal inferior vena cava (IVC) and aortic diameters and flow velocity were monitored by Doppler ultrasound and used to calculate the vessel diameter, blood flow, and shear stress. AVF were harvested, and expression of proteins was examined by proteomic analysis and immunofluorescence and of messenger RNA by quantitative polymerase chain reaction analysis. Results: At baseline, female mice weighed less and had lower IVC velocity and smaller magnitudes of shear stress, but there was no significant difference in IVC diameter and thickness. After AVF creation, both female and male mice had similar IVC dilation and thickening with no significant differences in IVC wall thickness at day 21. However, female mice had diminished AVF patency by day 42 (25.7% vs 64.3%; P = .039). During fistula remodeling, female mice had lower IVC mean velocity and shear stress magnitude and increased spectral broadening (days 0-21). Messenger RNA and protein expression of Krüppel-like factor 2, endothelial nitric oxide synthase, and vascular cell adhesion molecule 1 was similar at baseline in female and male mice but increased in the AVF only in male mice but not in female mice (day 21). Proteomic analysis of female and male mice detected 56 proteins expressed at significantly higher levels in the IVC of female mice and 67 proteins expressed at significantly higher levels in the IVC of male mice (day 7); function-specific analysis showed that the IVC of male mice overexpressed proteins that belong to pathways implicated in the regulation of vascular function, thrombosis, response to flow, and vascular remodeling. Conclusions: AVF in female mice have diminished patency, preceded by lower velocity, reduced magnitudes of shear stress, and less laminar flow during remodeling. There is also sex-specific differential expression of proteins involved in thrombosis, response to laminar flow, inflammation, and proliferation. These findings suggest that hemodynamic changes during fistula maturation may play an important role underlying the diminished rates of AVF utilization in women. : Clinical Relevance: Women have lower rates of arteriovenous fistula (AVF) utilization than men. Using a mouse AVF model that recapitulates human AVF maturation, we show that female mice have similar AVF remodeling but diminished patency. AVF remodeling in female mice is associated with reduced shear stress and laminar flow; lack of increased transcription and translation of several anti-inflammatory, antiproliferative, and laminar flow response proteins (endothelial nitric oxide synthase, Krüppel-like factor 2, and vascular cell adhesion molecule 1); and different patterns of expression of pathways that regulate thrombosis and venous remodeling. Identifying downstream targets involved in these mechanisms may improve AVF outcomes in female patients.

Objective: Central venous stenosis (CVS) is a major cause of arteriovenous fistula (AVF) failure. However, central veins are relatively inaccessible to study with conventional Doppler ultrasound methods. To understand mechanisms underlying AVF failure owing to CVS, an animal model was established that creates a stenosis distal to an AVF. We hypothesized that this mouse model will show comparable morphology and physiology to human CVS. Methods: An aortocaval fistula was created between the distal aorta and inferior vena cava (IVC); a stenosis was then created distal to the fistula by partial IVC ligation. Sham-operated animals, AVF without venous stenosis, and venous stenosis without AVF were used as controls. Physiologic properties of the IVC, both upstream and downstream of the stenosis, or the corresponding sites in models without stenosis, were assessed with ultrasound examination on days 0 to 21. The spectral broadening index was measured to assess the degree of disturbed shear stress. The IVC was harvested at day 21 and specimens were analyzed with immunofluorescence. Results: The IVC diameter of mice with an AVF and stenosis showed increased upstream (P = .013), but decreased downstream diameter (P = .001) compared with mice with an AVF but without a stenosis, at all postoperative times (days 3-21). IVC wall thickness increased in mice with an AVF, compared with IVC without an AVF (upstream of stenosis: 13.9 μm vs 11.0 μm vs 4.5 μm vs 3.9 μm; P = .020; downstream of stenosis: 6.0 μm vs 6.6 μm vs μm 4.5 μm vs 3.8 μm; P = .002; AVF with stenosis, AVF, stenosis, sham, respectively). AVF patency significantly decreased in mice with an AVF and stenosis by day 21 (50% vs 90%; P = .048). The IVC of mice with AVF and stenosis showed a venous waveform with pulsatility as well as enhanced velocity at and downstream of the stenosis; similar waveforms were observed in a human case of CVS. Downstream to the stenosis, the spectral broadening index was significantly higher compared with mice with AVF alone (1.06 vs 0.78; P = .011; day 21), and there was a trend towards less immunoreactivity of both Krüppel-like factor 2 and phosphorylated-endothelial nitric oxide synthase compared with mice with an AVF alone. Conclusions: Partial IVC ligation distal to a mouse aortocaval fistula alters the fistula diameter and wall thickness, decreases patency, and increases distal disturbed flow compared with fistulae without a distal stenosis. Our mouse model of stenosis distal to an AVF may be a faithful representation of human CVS that shows similar morphology and physiology, including disturbed shear stress. : Clinical Relevance: A mouse model of venous stenosis distal to an arteriovenous fistula shows similar Doppler waveforms as those observed in a human case of central venous stenosis. These mice retain disturbed shear stress in the vein distal to the fistula, characterized by a sustained increase of the spectral broadening index and diminished expression of proteins upregulated by laminar shear stress. This novel mouse model will enable investigation of the physiology and downstream molecular pathways involved in central venous stenosis in humans.

Interfacial shear stress transfer may occur in structural elements across concrete or between concrete and steel. The fundamental contributing parameters which improve the shear capacities are aggregate grading, compressive strength of concrete, type and area of the interfacial zone, and interfacial reinforcement pattern. During the event of a fire, these parameters are severely affected and mainly depend on the exposure level of the temperature and its duration. In the present investigation, the effect of elevated temperature on the interfacial Shear Transfer Capacity (STC) of Self-Compacting Concrete (SCC) was evaluated using shear (push-off) specimens. SCC was developed using Fly Ash (FA) and Ground Granulated Blast Furnace Slag (GGBFS) as Supplementary Cementitious Material (SCM). The study emphasises the proper understanding of degradation in shear strength of SCC exposed to elevated temperatures. Expanded Perlite Aggregate (EPA) is utilised as a partial replacement for fine aggregate. Also, a thermal protective coating is developed with Cement Perlite Plaster (CPP) for improving the performance of SCC. The European Federation of National Associations Representing for Concrete (EFNARC) guidelines were followed to ensure the workability of the developed SCC mix. Specimens were exposed to 30, 60, 90, and 120 min of heating durations following the International Organization for Standardization 834 (ISO 834) fire rating curve and tested to examine residual compressive strength, mass loss, STC after the natural air cooling process. The SCC specimens with EPA content have exhibited higher residual compressive strength and STC. All the protected SCC specimens coated with the CPP mixture contributed to retaining the original shear capacity by resisting the temperature. An empirical relationship was proposed to predict the residual STC of SCC after exposure to elevated temperature.

Background: The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited., Aims: The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses., Methods: In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support., Results: Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05)., Conclusions: Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Colonic motility plays a vital role in maintaining proper digestive function. The rhythmic contractions and relaxations facilitate various types of motor functions that generate both propulsive and non-propulsive motility modes which in turn generate shear stresses on the epithelial surface. However, the interplay between colonic mucus, shear stress, and epithelium remains poorly characterized. Here, we present a colonic computational model that describes the potential roles of mucus and shear stress in both homeostasis and ulcerative colitis (UC). Our model integrates several key features, including the properties of the mucus bilayer and faeces, intraluminal pressure, and crypt characteristics to predict the time-space mosaic of shear stress. We show that the mucus thickness which could vary based on the severity of UC, may significantly reduce the amount of shear stress applied to the colonic crypts and effect faecal velocity. Our model also reveals an important spatial shear stress variance in homeostatic colonic crypts that suggests shear stress may have a modulatory role in epithelial cell migration, differentiation, apoptosis, and immune surveillance. Together, our study uncovers the rather neglected roles of mucus and shear stress in intestinal cellular processes during homeostasis and inflammation., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Endothelial cells are sensitive to mechanical stress and respond differently to oscillatory flow versus unidirectional flow. This review highlights the mechanisms by which a wide range of unidirectional laminar shear stress induces activation of the redox sensitive antioxidant transcription factor nuclear factor-E2-related factor 2 (Nrf2) in cultured endothelial cells. We propose that fibroblast growth factor-2 (FGF-2), brain-derived neurotrophic factor (BDNF) and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) are potential Nrf2 activators induced by laminar shear stress. Shear stress-dependent secretion of FGF-2 and its receptor-mediated signaling is tightly controlled, requiring neutrophil elastase released by shear stress, αvβ3 integrin and the cell surface glycocalyx. We speculate that primary cilia respond to low laminar shear stress (15 dyn/cm2) induces vesicular exocytosis of BDNF from endothelial cells, and we propose that BDNF via the p75NTR receptor could induce CK2-mediated Nrf2 activation. Unidirectional laminar shear stress upregulates gene expression of FGF-2 and BDNF and generation of 15d-PGJ2, which cooperate in sustaining Nrf2 activation to protect endothelial cells against oxidative damage.

Thermomechanically active shape-programmable elastomer microparticles are very promising for development of particulate composites with unique operational properties, which could be attractive for various applications, e.g., in 3D printing. Liquid crystal elastomers are one of the suitable candidate materials due to their remarkable spontaneous shape change response. Performed rheological and thermomechanical tests demonstrate that shear stress can be used to efficiently manipulate the nematic order-driven morphology of liquid crystal elastomer microparticles (μLCEs). Specifically, by exploiting the soft-elasticity character of the material through manipulation of shear amplitude time profile, the nematic director can be oriented along the flow, which results in alignment of microparticles. Using this method, a suspension of well-aligned, thermomechanically elongated monodomain μLCEs can be created by shear stress-assisted cooling. Although the alignment can be lost in absence of persistent flow, it is restored instantaneously on re-application of the flow. The reason for this is the preservation of particle elongation at room temperature in zero flow. This shape memory can be erased by heating the system to the isotropic phase. Our work represents an important step forward in the development of a new generation of shape-programmable materials, which are potentially suitable for additive manufacturing of artefacts with anisotropic physical properties.

At cracked stage, the post-tensioned concrete beams resist shear through a different set of mechanisms, the accepted mechanisms are: interface shear transfer, dowel action of longitudinal reinforcements, shear transfer in compression zone, transversal reinforcements, and vertical component of the force in the draped of prestressing strands. To increase the shear capacity in such beams, special shear reinforcements can be used. This paper presents the results of an experimental investigation on shear strength for bonded post-tensioned concrete beams (PTB) reinforced with inverted-U shaped reinforcement; those results were compared with beams provided with stirrups reinforcements. Based on ACI code, the nominal shear stress in transversal reinforcement is limited to 8 fc' psi (0.67 fc' MPa), but however it does not differentiate between the types of shear reinforcements. The results indicate that the nominal shear stress in inverted-U shaped and stirrups reinforcements are 14.4 fc' psi (1.2 fc' MPa) and 12.72 fc' psi (1.06 fc' MPa), which it gives approximately 13 % increase in shearing strength. Good correlations exist between the predicted and the actual experimental results.

Magnesium/Ceria nanocomposites (Mg/xCeO 2 NCs (x = 0.5 %, 1 % and 1.5 %)) prepared by using powder metallurgy and microwave sintering method are assessed for their corrosion rate for a period of 28 days. As per the immersion tests results, the addition of ceria nanoparticles to pure Mg, brought about a noteworthy improvement to corrosion resistance. A corrosion rate of approximately 0.84 mm/year for Mg/0.5CeO 2 and 0.99 mm/year for Mg/1.0CeO 2 nanocomposites were observed. Another aspect of the study involves employing the simulation method i.e. finite element analysis (FEA) to compare the stress distribution in magnesium-ceria nanocomposite based screws and circular bars especially for Mg/0.5CeO 2 and Mg/1.0CeO 2 . Further, the simulation also gives a perception of the impact of masticatory forces, the biting force and shear stress exerted on the Mg/0.5CeO 2 and Mg/1.0CeO 2 based screws. The simulations results show that the screws showed an acceptable level of stresses for a biting force up to 300 N. The circular bar as well kept its stresses at acceptable levels for the same load of 300N. The shear stress results indicated that a biting force up to 602 N can be safely absorbed by Mg/0.5CeO 2 screw. The comprehensive approach allows for a better understanding of the corrosion behavior, stress distribution, and mechanical properties of the Mg/CeO 2 nanocomposites, enabling the development of effective temporary implants for craniofacial trauma fixation that can withstand normal physiological forces during mastication. The study reported in this paper aims to target Mg/xCeO 2 NCs for temporary implants for craniofacial trauma fixation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98.3% in the high shear stress group (45 dyn/cm 2 ). Furthermore, we found that Piezo1 served as a crucial mechanosensor for the differentiation and maturation of VELs. Mechanistically, the activation of Piezo1 by shear stress resulted in the influx of calcium ions, which in turn initiated the Akt signaling pathway and promoted the differentiation of hiPSCs into mature VELs. Moreover, VELs cultured on decellularized heart valves (DHVs) exhibited a notable propensity for proliferation, robust adhesion properties, and antithrombotic characteristics, which were dependent on the activation of the Piezo1 channel. Overall, our study demonstrated that proper shear stress activated the Piezo1 channel to facilitate the differentiation and maturation of hiPSC-VELs via the Akt pathway, providing a potential cell source for regenerative medicine, drug screening, pathogenesis, and disease modeling. STATEMENT OF SIGNIFICANCE: This is the first research that systematically analyzes the effect of shear stress on valvular endothelial-like cells (VELs) derived from human induced pluripotent stem cells (hiPSCs). Mechanistically, unidirectional shear stress activates Piezo1, resulting in an elevation of calcium levels, which triggers the Akt signaling pathway and then facilitates the differentiation of functional maturation VELs. After exposure to shear stress, the VELs exhibited enhanced proliferation, robust adhesion capabilities, and antithrombotic characteristics while being cultured on decellularized heart valves. Thus, it is of interest to develop hiPSCs-VELs using shear stress and the Piezo1 channel provides insights into the functional maturation of valvular endothelial cells, thereby serving as a catalyst for potential applications in the development of therapeutic and tissue-engineered heart valves in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: We sought to assess the accuracy of a novel parameter proportional to the rod shear stress (RSS) in identifying patients at risk of rod fracture (RF) after surgery for correction of adult spinal deformity., Methods: We performed a retrospective medical record review of patients aged ≥18 years treated for adult spinal deformity between 2004 and 2014 with ≥24 months of follow-up. The primary outcome was RFs identified radiographically. Patient weight (w), number of instrumented levels (N), and minimum rod diameter (d) were recorded and used to calculate the RSS parameter (RSS=Nwd 2 ). Receiver operating characteristic curves were produced and the area under the curve (AUC ± 95% confidence interval [CI]) was calculated to compare this parameter's discriminative accuracy to that of its constituent variables. The sensitivity, specificity, and likelihood ratios (LRs) were calculated., Results: A total of 28 RF-positive and 154 RF-negative patients were included. The average age was 59.2 ± 9.6 years, and 93.4% were women. The RSS parameter produced the greatest AUC (0.73 ± 0.11). At an RSS cutoff of 30.1, it achieved a sensitivity of 71.4% and specificity of 71.4% (LR, 2.5; 95% CI, 1.8-3.5). The number of instrumented levels produced the next-greatest AUC (0.65 ± 0.12), with a sensitivity of 78.6% and specificity of 50.0% at a cutoff of 15 (LR, 1.6; 95% CI, 1.2-2.0)., Conclusions: The RSS is calculated using easily obtainable information and shows potential as a tool for predicting patient-specific risk of RF after spinal fusion. The number of instrumented levels also correlates strongly with the occurrence of RFs and is not significantly less accurate than the RSS. A larger sample size and prospective validation would be useful in determining with greater confidence which parameter is superior for predicting RFs after spinal fusion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endothelial nitric oxide (NO) is a critical mediator of vascular function and vascular remodeling. NO is produced by endothelial nitric oxide synthase (eNOS), which is activated by calcium (Ca2+)-dependent and Ca2+-independent pathways. Here, we report that neurogranin (Ng), which regulates Ca2+-calmodulin (CaM) signaling in the brain, is uniquely expressed in endothelial cells (EC) of human and mouse vasculature, and is also required for eNOS regulation. To test the role of Ng in eNOS activation, Ng knockdown in human aortic endothelial cells (HAEC) was performed using Ng SiRNA along with Ng knockout (Ng −/−) in mice. Depletion of Ng expression decreased eNOS activity in HAEC and NO production in mice. We show that Ng expression was decreased by short-term laminar flow and long-them oscillating flow shear stress, and that Ng siRNA with shear stress decreased eNOS expression as well as eNOS phosphorylation at S1177. We further reveled that lack of Ng expression decreases both AKT-dependent eNOS phosphorylation, NF-κB-mediated eNOS expression, and promotes endothelial activation. Our findings also indicate that Ng modulates Ca2+-dependent calcineurin (CaN) activity, which suppresses Ca2+-independent AKT-dependent eNOS signaling. Moreover, deletion of Ng in mice also reduced eNOS activity and caused endothelial dysfunction in flow-mediated dilation experiments. Our results demonstrate that Ng plays a crucial role in Ca2+-CaM-dependent eNOS regulation and contributes to vascular remodeling, which is important for the pathophysiology of cardiovascular disease.

Fluid shear stress (FSS) induces a series of biochemical responses in osteoblasts, and this “mechanoresponse” regulates their survival, proliferation and differentiation. However, the events in cells immediately after FSS application are unclear, and how biochemical signals from soluble factors modify the mechanoresponses is largely unknown. We used the orbital shaking method, instead of the frequently used parallel plate method, to examine activation of ERK and AKT by FSS for detailed tracking of its temporal transition. We found that ERK activation by orbital shaking was biphasic. The early phase was independent of Ca2+, PI3-kinase, and Rho kinase but required RAF activity. The late phase was dependent on Ca2+ but not RAF. These results suggest that the superior time-resolving capability of the orbital shaking method to separate the previously unrecognized Ca2+-independent early phase of ERK activation from the late phase. We also found that a certain combination of serum starvation and medium renewal affected ERK activation by FSS, suggesting that a soluble factor(s) may be secreted during serum starvation, which modified the phosphorylation level of ERK. These findings revealed novel aspects of the osteoblastic mechanoresponses and indicated that the orbital shaking method would be a useful, complementary alternative to the parallel plate method for certain types of study on cellular mechanoresponses.

The aim of this article was to analyze the rotational flow of an Oldroyd-B fluid with fractional derivatives, induced by an infinite circular cylinder that applies a constant couple to the fluid. Such kind of problem in the settings of fractional derivatives has not been found in the literature. The solutions are based on an important remark regarding the governing equation for the non-trivial shear stress. The solutions that have been obtained satisfy all imposed initial and boundary conditions and can easily be reduced to the similar solutions corresponding to ordinary Oldroyd-B, fractional/ordinary Maxwell, fractional/ordinary second-grade, and Newtonian fluids performing the same motion. The obtained results are expressed in terms of Newtonian and non-Newtonian contributions. Finally, the influence of fractional parameters on the velocity, shear stress and a comparison between generalized and ordinary fluids is graphically underlined.

Background and Aims: Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries., Methods: Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS & MWS) and changes in coronary wall (ΔWT & ΔLRNC) were studied using linear mixed models., Results: In plaque-free sectors, higher MWS (p < 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p < 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 0.01)., Conclusions: In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joost Daemen received institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Biofouling is a specific lifestyle including both marine prokaryotic and eukaryotic communities. Hydrodynamics are poorly studied parameters affecting biofouling formation. This study aimed to investigate how water dynamics in the Etel Estuary (Northwest Atlantic coasts of France) influences the colonization of artificial substrates. Hydrodynamic conditions, mainly identified as shear stress, were characterized by measuring current velocity, turbulence intensity and energy using Acoustic Doppler Current Profiler (ADCP). One-month biofouling was analyzed by coupling metabarcoding (16S rRNA, 18S rRNA and COI genes), untargeted metabolomics (liquid chromatography coupled with high-resolution mass spectrometry, LC-HRMS) and characterization of the main biochemical components of the microbial exopolymeric matrix. A higher richness was observed for biofouling communities (prokaryotes and eukaryotes) exposed to the strongest currents. Ectopleura (Cnidaria) and its putative symbionts Endozoicomonas (Gammaproteobacteria) were dominant in the less dynamic conditions. Eukaryotes assemblages were specifically shaped by shear stress, leading to drastic changes in metabolite profiles. Under high hydrodynamic conditions, the exopolymeric matrix increased and was composed of 6 times more polysaccharides than proteins, these latter playing a crucial role in the adhesion and cohesion properties of biofilms. This original multidisciplinary approach demonstrated the importance of shear stress on both the structure of marine biofouling and the metabolic response of these complex communities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Portas reports financial support was provided by French National Research Agency. Portas reports financial support was provided by Horizon Europe., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The aim of this contribution was to present a study based on the determination and the visualization of the structural deformations due to the contact of slipping between the disc and the pads. The results of the calculations of the contact described in this work relate to displacements, Von Mises stress on the disc, and contact pressures on the inner and outer pad at various moments of simulation. We first proceed to view the meshed models and predicting variations of tensile or compressive stress normal to the plane and shear stress in rotating disc and ring bodies. One precedes then the influence of some parameters on the computation results such as rotation of the disc, the smoothness of the mesh, the material of the brake pads and the friction coefficient entering the disc and the pads, the number of revolutions and the material of the disc, the pad groove.