Development of in vitro microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two in vitro microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an in vitro microfluidic system. The performance of the two systems was verified by numerical simulations and in vitro experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca2+, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model.

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

Study on the hemodynamic effects of different pulsatile working modes of a rotary blood pump using a microfluidic platform that realizes in vitro cell culture effectively.

Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure.

Microfluidic characterization of single-cell biophysical properties and the applications in cancer diagnosis.

Single-cell biophysical properties play a crucial role in regulating cellular physiological states and functions, demonstrating significant potential in the fields of life sciences and clinical diagnostics. Therefore, over the last few decades, researchers have developed various detection tools to explore the relationship between the biophysical changes of biological cells and human diseases. With the rapid advancement of modern microfabrication technology, microfluidic devices have quickly emerged as a promising platform for single-cell analysis offering advantages including high-throughput, exceptional precision, and ease of manipulation. Consequently, this paper provides an overview of the recent advances in microfluidic analysis and detection systems for single-cell biophysical properties and their applications in the field of cancer. The working principles and latest research progress of single-cell biophysical property detection are first analyzed, highlighting the significance of electrical and mechanical properties. The development of data acquisition and processing methods for real-time, high-throughput, and practical applications are then discussed. Furthermore, the differences in biophysical properties between tumor and normal cells are outlined, illustrating the potential for utilizing single-cell biophysical properties for tumor cell identification, classification, and drug response assessment. Lastly, we summarize the limitations of existing microfluidic analysis and detection systems in single-cell biophysical properties, while also pointing out the prospects and future directions of their applications in cancer diagnosis and treatment.

Temperature-mediated diffusion of nanoparticles in semidilute polymer solutions.

The temperature is often a critical factor affecting the diffusion of nanoparticles in complex physiological media, but its specific effects are still to be fully understood. Here, we constructed a temperature-regulated model of semidilute polymer solution and experimentally investigated the temperature-mediated diffusion of nanoparticles using the particle tracking method. By examining the ensemble-averaged mean square displacements (MSDs), we found that the MSD grows gradually as the temperature increases while the transition time from sublinear to linear stage in MSD decreases. Meanwhile, the temperature-dependent measured diffusivity of the nanoparticles shows an exponential growth. We revealed that these temperature-mediated changes are determined by the composite effect of the macroscale property of polymer solution and the microscale dynamics of polymer chain as well as nanoparticles. Furthermore, the measured non-Gaussian displacement probability distributions were found to exhibit non-Gaussian fat tails, and the tailed distribution is enhanced as the temperature increases. The non-Gaussianity was calculated and found to vary in the same trend with the tailed distribution, suggesting the occurrence of hopping events. This temperature-mediated non-Gaussian feature validates the recent theory of thermally induced activated hopping. Our results highlight the temperature-mediated changes in diffusive transport of nanoparticles in polymer solutions and may provide the possible strategy to improve drug delivery in physiological media.

A mathematical model for intracellular NO and ROS dynamics in vascular endothelial cells activated by exercise-induced wall shear stress.

Vascular endothelial cells (ECs) residing in the innermost layer of blood vessels are exposed to dynamic wall shear stress (WSS) induced by blood flow. The intracellular nitric oxide (NO) and reactive oxygen species (ROS) in ECs modulated by the dynamic WSS play important roles in endothelial functions. Mathematical modeling is a popular methodology for biophysical studies. It can not only explain existing cell experiments, but also reveal the underlying mechanism. However, the previous mathematical models of NO dynamics in ECs are limited to the static WSS induced by constant flow, while arterial blood flow is a periodic pulsatile flow with varying amplitude and frequency at different exercise intensities. In this study, a mathematical model of intracellular NO and ROS dynamics activated by dynamic WSS based on the in vitro cell experiments is developed. With the hypothesis of the viscoelastic body, the Kelvin model is adopted to simulate the mechanosensors on EC. Thus, the NO dynamics activated by dynamic shear stresses induced by constant flow, pulsatile flow, and oscillatory flow are analyzed and compared. Moreover, the roles of ROS have been considered for the first time in the modeling of NO dynamics in ECs based on the analysis of cell experiments. The predictions of the proposed model coincide fairly well with the experimental data when ECs are subjected to exercise-induced WSS. The mechanism is elucidated that WSS induced by moderate-intensity exercise is most favorable to NO production in ECs. This study can provide valuable insights for further study of NO and ROS dynamics in ECs and help develop appropriate exercise regimens for improving endothelial functions.

Fabricating a multi-component microfluidic system for exercise-induced endothelial cell mechanobiology guided by hemodynamic similarity.

Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments. First, based on the equivalent of blood pressure (BP) and wall shear stress (WSS) waveforms, we establish a hemodynamic similarity principle to efficiently map the input impedance in vivo to that in vitro, after which the multi-component microfluidic system is designed and fabricated using a lumped parameter hemodynamic model. Second, numerical simulation and experimental studies are carried out to validate the performance of the designed microfluidic system. Finally, the intracellular Ca2+ responses after exposure to different intensities of exercise-induced BP and WSS waveforms are measured to improve the reliability of EC mechanobiological studies using the designed microfluidic system. Overall, the proposed hemodynamic similarity principle can guide the fabrication of a multi-component microfluidic system for endothelial cell mechanobiology.

Ginkgo biloba L. extract prevents steroid-induced necrosis of the femoral head by rescuing apoptosis and dysfunction in vascular endothelial cells via the PI3K/AKT/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. extract (EGb) is one of the world's most extensively used herbal medicines. Due to the diverse pharmacological properties of EGb, it has been used in the treatment of neurological illnesses, as well as cardiovascular and cerebrovascular ailments. However, the effect and pharmacological mechanism of EGb on steroid-induced necrosis of the femoral head (SINFH) are still unclear. AIM OF THE STUDY: SINFH remains a challenging problem in orthopedics. Previous investigations have shown that EGb has the potential to reduce the occurrence of SINFH. The goal was to determine the effect and mechanism of EGb in preventing SINFH by inhibiting apoptosis and improving vascular endothelial cells (VECs) functions. MATERIALS AND METHODS: CCK-8, nitric oxide (NO) production and flow cytometry were used to determine the cell apoptosis and function. The scratch and angiogenesis tests assessed migration and tube formation. Western blot analysis detected the expressions of apoptosis-related proteins and PI3K/AKT/eNOS pathway-related proteins. Apoptosis and angiogenesis were also detected treated with the inhibitors. A mouse model of SINFH was established. Paraffin section was used to determine the necrotic pathology and apoptosis. Vessels in the femoral heads were assessed by immunofluorescence staining. RESULTS: When stimulated by methylprednisolone (MPS), cell viability, NO generation and tube formation were decreased, the apoptotic rate increased. Simultaneously, MPS decreased the expression levels of p-PI3K, p-AKT, and p-eNOS. EGb increased the expression levels of these proteins, restrained apoptosis, and restored cell functions. The addition of the inhibitors decreased anti-apoptotic effect and angiogenesis. In addition, when compared to the model mice, there were fewer empty lacunae and normal trabecular arrangement after taking different doses of EGb. The protective effect was also confirmed by the vascular quantitative analysis in vivo. CONCLUSION: This study established that EGb increased endothelial cell activity and inhibited apoptosis and function loss induced by MPS, elucidating the effect and molecular mechanism of EGb on early SINFH.

Vortex evolution patterns for flow of dilute polymer solutions in confined microfluidic cavities.

Flow instability in confined cavities has attracted extensive interest due to its significance in many natural and engineering processes. It also has applications in microfluidic devices for biomedical applications including flow mixing, nanoparticle synthesis, and cell manipulation. The recirculating vortex that characterizes the flow instability is regulated by the fluid rheological properties, cavity geometrical characteristics, and flow conditions, but there is a lack of quantitative understanding of how the vortex evolves as these factors change. Herein, we experimentally study the flow of dilute polymer solutions in confined microfluidic cavities and focus on a quantitative characterization of the vortex evolution. Three typical patterns of vortex evolution are identified in the cavity flow of dilute polymer solutions over a wide range of flow conditions. The geometrical characteristics of the cavity are found to have little effect on the patterns of vortex evolution. The geometry-independent patterns of vortex evolution provide us an intuitive paradigm, from which the interaction and competition among inertial, elastic and shear-thinning effects in these cavity-induced flow instabilities are clarified. These results extend our understanding of the flow instability of complex fluids in confined cavities, and provide useful guidelines for the design of cavity-structured microfluidic devices and their applications.

Clinical Application of the Musculoperiosteal Iliac Flap for Osteonecrosis of the Femoral Head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) often affects young, active patients, and the femoral head's preservation is the primary goal of treatment for this disease. Vascularized iliac crest bone grafting is one of the many vascularized procedures used in treating ONHF. In some cases, we selectively performed this procedure using the musculoperiosteal iliac flap with the ascending branch of the lateral femoral circumflex artery for ONFH treatment. METHODS: Twelve patients (12 hips) with nontraumatic femoral head necrosis underwent musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery. The Harris Hip Score (HHS), visual analog scale score, and double-hip X-ray findings were used to analyze hip function changes within 10 days preoperatively and 6 and 12 months postoperatively. RESULTS: The mean HHS increased from 52.33 ± 3.34 preoperatively to 65.92 ± 5.04 6 months postoperatively and 79.75 ± 3.84 12 months postoperatively, and the data showed a statistical significance difference between preoperative and postoperative (F = 131.90, P < 0.01). The HHS at 6 and 12 months after surgery were significantly different (P < 0.01). The visual analog scale score showed the same trend. The x-ray of hip joints at 6 and 12 months after surgery showed that the femoral heads' shape and contour were good, femoral heads did not collapse, and the transferred bone flaps healed well. CONCLUSIONS: Musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery may be an effective method with a high clinical success rate for treating young patients with early to midstage ONFH.

A microfluidic system for precisely reproducing physiological blood pressure and wall shear stress to endothelial cells.

To reproduce hemodynamic stress microenvironments of endothelial cells in vitro is of vital significance, by which one could exploit the quantitative impact of hemodynamic stresses on endothelial function and seek innovative approaches to prevent circulatory system diseases. Although microfluidic technology has been regarded as an effective method to create physiological microenvironments, a microfluidic system to precisely reproduce physiological arterial hemodynamic stress microenvironments has not been reported yet. In this paper, a novel microfluidic chip consisting of a cell culture chamber with on-chip afterload components designed by the principle of input impedance to mimic the global hemodynamic behaviors is proposed. An external feedback control system is developed to accurately generate the input pressure waveform. A lumped parameter hemodynamic model (LPHM) is built to represent the input impedance to mimic the on-chip global hemodynamic behaviors. Sensitivity analysis of the model parameters is also elaborated. The performance of reproducing physiological blood pressure and wall shear stress is validated by both numerical characterization and flow experiment. Investigation of intracellular calcium ion dynamics in human umbilical vein endothelial cells is finally conducted to demonstrate the biological applicability of the proposed microfluidic system.

A microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow.

Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

Modeling of Endothelial Calcium Responses within a Microfluidic Generator of Spatio-Temporal ATP and Shear Stress Signals.

Intracellular calcium dynamics play essential roles in the proper functioning of cellular activities. It is a well known important chemosensing and mechanosensing process regulated by the spatio-temporal microenvironment. Nevertheless, how spatio-temporal biochemical and biomechanical stimuli affect calcium dynamics is not fully understood and the underlying regulation mechanism remains missing. Herein, based on a developed microfluidic generator of biochemical and biomechanical signals, we theoretically analyzed the generation of spatio-temporal ATP and shear stress signals within the microfluidic platform and investigated the effect of spatial combination of ATP and shear stress stimuli on the intracellular calcium dynamics. The simulation results demonstrate the capacity and flexibility of the microfluidic system in generating spatio-temporal ATP and shear stress. Along the transverse direction of the microchannel, dynamic ATP signals of distinct amplitudes coupled with identical shear stress are created, which induce the spatio-temporal diversity in calcium responses. Interestingly, to the multiple combinations of stimuli, the intracellular calcium dynamics reveal two main modes: unimodal and oscillatory modes, showing significant dependence on the features of the spatio-temporal ATP and shear stress stimuli. The present study provides essential information for controlling calcium dynamics by regulating spatio-temporal biochemical and biomechanical stimuli, which shows the potential in directing cellular activities and understanding the occurrence and development of disease.

The intracellular calcium dynamics in a single vascular endothelial cell being squeezed through a narrow microfluidic channel.

Revealing the mechanisms underlying the intracellular calcium responses in vascular endothelial cells (VECs) induced by mechanical stimuli contributes to a better understanding for vascular diseases, including hypertension, atherosclerosis, and aneurysm. Combining with experimental measurement and Computational Fluid Dynamics simulation, we developed a mechanobiological model to investigate the intracellular [Ca2+] response in a single VEC being squeezed through narrow microfluidic channel. The time-dependent cellular surface tension dynamics was quantified throughout the squeezing process. In our model, the various Ca2+ signaling pathways activated by mechanical stimulation is fully considered. The simulation results of our model exhibited well agreement with our experimental results. By using the model, we theoretically explored the mechanism of the two-peak intracellular [Ca2+] response in single VEC being squeezed through narrow channel and made some testable predictions for guiding experiment in the future.

Acute Effects of Different Intensities of Cycling Acute Exercise on Carotid Arterial Apparent Elasticity and Hemodynamic Variables.

BACKGROUND: Cardiovascular disease (CVD) is closely related to arterial elasticity and hemodynamics. Exercises have been reported to immediately decrease arterial apparent elasticity and regulate hemodynamic variables. However, the relationship between them and exercise intensity remains elusive. The purpose of this study was to determine the acute effects of different intensities of acute cycling exercise on carotid arterial apparent elasticity and hemodynamics. METHODS: 32 healthy men (age: 19.4 ± 0.6 years) attended the laboratory on five occasions and completed cycling acute exercise for 20 minutes at five intensities (40%, 50%, 60%, 70%, and 80% heart rate reserve (HRR)). At the right carotid artery, center-line velocity and arterial inner diameter waveforms were examined before and immediately after exercise. Based upon the measured data, the classical hemodynamic theory was used to calculate the apparent elasticity and the local hemodynamic variables. RESULTS: The arterial apparent stiffness and the apparent elastic modulus following acute cycling exercise at 60% to 80% HRR were significantly higher than baseline. The mean center-line velocity accelerated from 50% to 80% HRR, but no intensity of intervention altered mean blood flow. Immediately after intervention, the mean wall shear stress and oscillatory shear index increased. CONCLUSIONS: Aerobic cycling intervention, with intensity from 40% to 80% HRR, did not change the brain blood supply. A bout of cycling intervention decreased apparent elasticity, and there was an intensity-dependent effect on apparent elasticity and hemodynamic variables. This study would provide referable data for the further study on the effects of aerobic exercise on arterial hemodynamics and elasticity and underlying physiological mechanisms.

Breakup Dynamics of Semi-dilute Polymer Solutions in a Microfluidic Flow-focusing Device.

Droplet microfluidics involving non-Newtonian fluids is of great importance in both fundamental mechanisms and practical applications. In the present study, breakup dynamics in droplet generation of semi-dilute polymer solutions in a microfluidic flow-focusing device were experimentally investigated. We found that the filament thinning experiences a transition from a flow-driven to a capillary-driven regime, analogous to that of purely elastic fluids, while the highly elevated viscosity and complex network structures in the semi-dilute polymer solutions induce the breakup stages with a smaller power-law exponent and extensional relaxation time. It is elucidated that the elevated viscosity of the semi-dilute solution decelerates filament thinning in the flow-driven regime and the incomplete stretch of polymer molecules results in the smaller extensional relaxation time in the capillary-driven regime. These results extend the understanding of breakup dynamics in droplet generation of non-Newtonian fluids and provide guidance for microfluidic synthesis applications involving dense polymeric fluids.

Separation of micro and sub-micro diamagnetic particles in dual ferrofluid streams based on negative magnetophoresis.

In the present study, we numerically demonstrate an approach for separation of micro and sub-micro diamagnetic particles in dual ferrofluid streams based on negative magnetophoresis. The dual streams are constructed by an intermediate sheath flow, after which the negative magnetophoretic force induced by an array of permanent magnets dominates the separation of diamagnetic particles. A simple and efficient numerical model is developed to calculate the motions of particles under the action of magnetic field and flow field. Effects of the average flow velocity, the ratio of sheath fluid flow to sample fluid flow, the number of the magnet pair as well as the position of magnet pair are investigated. The optimal parametric condition for complete separation is obtained through the parametric analysis, and the separation principle is further elucidated by the force analysis. The separation of smaller micro and sub-micro diamagnetic particles is finally demonstrated. This study provides an insight into the negative magnetophoretic phenomenon and guides the fabrication of feasible, low-cost diagnostic devices for sub-micro particle separation.

Precise generation of dynamic biochemical signals by controlling the programmable pump in a Y-shaped microfluidic chip with a "christmas tree" inlet.

The generation of dynamic biochemical signals in a microfluidic control system is of importance for the study of the interaction between biological cells and their niches. However, most of microfluidic control systems are not able to provide dynamic biochemical signals with high precision and stability due to inherent mechanical vibrations caused by the actuators of the programmable pumps. In this paper, we propose a novel microfluidic feedback control system integrating an external feedback control system with a Y-shaped microfluidic chip with a "Christmas tree" inlet. The Proportional Integral Derivative (PID) controller is implemented to reduce the influence of vibrations. In order to regulate the control parameters efficiently, a mathematical model is built to describe the actuator of the programmable pump, in which a fractional-order model is utilized. Both simulation and experimental studies are carried out, confirming that the microfluidic feedback control system can precisely and stably generate desired dynamic biochemical signals.

ROS and NO Dynamics in Endothelial Cells Exposed to Exercise-Induced Wall Shear Stress.

INTRODUCTION: Intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels are associated with vascular homeostasis and diseases. Exercise can modulate ROS and NO production through increasing frequency and magnitude of wall shear stress (WSS). However, the details of ROS and NO production in endothelial cells and their interplay under WSS induced by exercise at different intensities remain unclear. METHODS: In this study, we developed an in vitro multicomponent nonrectangular flow chamber system to simulate pulsatile WSS waveforms induced by moderate and high intensity exercise. Furthermore, the dynamic responses of ROS and NO in endothelial cells and the relationship between ROS and NO were investigated under the WSS induced by different intensity exercise. RESULTS: After exposing to WSS induced by moderate intensity exercise, endothelial cells produced more NO than those under high intensity exercise-induced WSS. In this process, ROS was found to play a dual role in the generation of intracellular NO. Under WSS induced by moderate intensity exercise, modest elevated ROS promoted NO production, whereas excessive ROS in endothelial cells exposed to WSS induced by high intensity exercise attenuated NO bioavailability. Interestingly, antioxidant N-acetylcysteine (NAC) could increase NO production under WSS induced by high intensity exercise. CONCLUSIONS: Our results provide some cues for selecting appropriate exercise intensities and elevating benefits of exercise on endothelial function. Additionally, owing to the consistency of our results and some in vivo phenomena, this flow chamber system may serve as an in vitro exercise model of arterial vessel for future studies.

A Capillary-Evaporation Micropump for Real-Time Sweat Rate Monitoring with an Electrochemical Sensor.

Sweat collection and real time monitoring of sweat rate play essential roles in physiology monitoring and assessment of an athlete's performance during exercise. In this paper, we report a micropump for sweat simulant collection based on the capillary-evaporation effect. An electrochemical sensor is integrated into the micropump, which monitors the flow rate in real-time by detecting the current using three electrodes. The evaporation rate from micropore array, equivalent to the sweat rate, was theoretically and numerically investigated. The designed micropump yields the maximum collection rate as high as 0.235 µ L/min. In addition, the collection capability of the micropump was validated experimentally; the flow rate through the microchannel was further detected in real-time with the electrochemical sensor. The experimental maximum collection rate showed good consistency with the theoretical data. Our proposed device shows the potential for sweat collection and real-time monitoring of sweat rate, which is a promising candidate for being a wearable platform for real-time physiology and performance monitoring during exercise.