Essentials
ARHGEF10 single‐nucleotide polymorphism provides risk of ischemic and atherothrombotic stroke.
The role of ARHGEF10 in platelet function was examined using ARHGEF10 knockout mice.
ARHGEF10 ...deficiency inhibits platelet function and arterial thrombus formation.
ARHGEF10 knockout protects mice from stroke‐induced infarction.
Summary
Background
ARHGEF10, a member of the Rho guanine nucleotide exchange factor (GEF) family, stimulates Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors, such as cell polarity, cytoskeletal organization, and gene transcription. ARHGEF10 single‐nucleotide polymorphisms are linked to the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown.
Objective
To examine the role of ARHGEF10 in platelet function.
Methods
ARHGEF10−/−were generated. We examined the in vitro and in vivo effects of ARHGEF10 knockout on platelet function and arterial thrombosis formation.
Results
ARHGEF10−/− mice had normal platelet counts, but showed altered aggregation in response to thrombin, collagen, ADP, protease‐activated receptor‐4 peptide, and U46619 stimulation. ARHGEF10 knockout influenced platelet spreading on fibrinogen‐coated surfaces, and caused the platelets to show less lamellipodia‐like extension than wild‐type platelets. ARHGEF10 knockout also inhibited platelet clot retraction induced by thrombin stimulation. ARHGEF10 knockout resulted in prolonged tail bleeding time and inhibited the stable thrombus formation induced by FeCl3 in the carotid artery.
Conclusions
ARHGEF10 serves as an important regulator in platelet shape change, spreading, and aggregation. Moreover, ARHGEF10 also plays an important role in arterial thrombosis formation.
Summary
Background
Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in ...hemostasis has not yet been elucidated.
Objectives
The hemostatic activity of Reelin is investigated and defined in this study.
Methods
The interplay of Reelin with coagulation components was elucidated by far‐Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis‐related analyses of Reelin‐deficient mice and plasma were also performed.
Results
Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin β1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nm, respectively. Reelin‐deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern.
Conclusions
By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.
Due to the demand for reduced energy consumption by transportation vehicles, lighter weight high-entropy alloys (with density comparable to that of commercial Ti alloys around 4.5–5 g/cm3) are ...attracting more attention in terms of alloy design and application as structural materials. In this study, a nonequiatomic quaternary alloy system, Tix(AlCrNb)100-x, was designed through the calculation of phase diagrams. Simulation results reveal that a single body-centered cubic (BCC) phase can be formed and can be stable at temperatures above 950 °C. Accordingly, a series of Tix(AlCrNb)100-x (x = 45–80) alloys containing a BCC structure were prepared through vacuum arc melting and rapid cooling. The designed alloys can exhibit desirable mechanical properties with high compression yield strength about 1500 MPa, high compression fracture strength about 1800 MPa and high compression plasticity more than 30% at room temperature. Moreover, the Ti65 alloy can demonstrate a tensile strength of 1200 MPa with a tensile elongation of 32%, after a homogenization treatment for 24 h. The specific compression and tensile strength can reach 0.36 and 0.24 GPa cm3/g.
•Novel alloys designing of light weight high entropy alloys by calculation of phase diagrams.•High strength with high ductility medium-entropy alloys (MEAs).•Both of the as-cast and homogenized samples possess BCC structures and perform superior tensile strength as well plasticity.
•Previous comparisons of metaraminol, ephedrine and phenylephrine show equipoise.•A meta-analysis of metaraminol use during spinal anaesthesia at caesarean section.•Metaraminol appears superior to ...ephedrine for the prevention of feto-maternal complications.•Metaraminol is associated with better umbilical arterial pH values than phenylephrine.•Metaraminol is a suitable vasopressor for use in obstetric anaesthesia.
During caesarean section, the use of a vasopressor is often required to achieve haemodynamic stability of the parturient. Metaraminol is a vasopressor used in this context in some countries. However, the differences between metaraminol and other vasopressors remain unclear.
A search of the PubMed, Cochrane Library, and Embase databases was performed to identify randomised controlled trials comparing the use of metaraminol with other vasopressors during spinal anaesthesia at caesarean section. The selected studies were subjected to meta-analysis and risk-of-bias assessment.
Four randomised, controlled trials met the selection criteria and 409 parturients who underwent an elective caesarean section were included in this meta-analysis. The quality of these trials was good. Metaraminol was associated with higher umbilical arterial pH (standardised mean difference SMD 0.82, 95% CI 0.01 to 1.62, P=0.05); a lower incidence of fetal acidosis (RR 0.08, 95% CI 0.01 to 0.63, P=0.02); and a lower incidence of nausea or vomiting (RR 0.16, 95% CI 0.04 to 0.57, P=0.0005) than was ephedrine. Metaraminol resulted in higher umbilical arterial pH (SMD 0.42, 95% CI 0.15 to 0.68, P=0.002) but a higher incidence of reactive hypertension (RR 1.80, 95% CI 1.32 to 2.46, P=0.0002) than did phenylephrine.
The results of this study showed that for spinal anaesthesia at elective caesarean section, metaraminol may be a more suitable vasopressor than ephedrine and its effects are at least not inferior to those of phenylephrine.
The soil‐water characteristic curve (SWCC) plays an essential role in the analysis of the shear strength, deformation, hydraulic conductivity, and aqueous diffusion of unsaturated soils. A review of ...methods proposed for fitting the main SWCCs is presented. The methods can be categorized into three groups, namely, (i) empirical methods, (ii) domain methods, and (iii) theoretical methods. A hysteretic model considering the contact angle hysteresis is proposed for fitting the main SWCCs based on a theoretical method. The model links the physical quantities at the micro‐and macro‐scale. Specifically, a modified expression describing the relationship between the volume of the liquid bridge and the water content is derived, and the contact angle hysteresis behavior is modeled based on the study of total thermodynamic potential energy. The model has a clear physical meaning, and the parameters can be obtained easily. Comparisons of the model simulation and experimental data show that the proposed model accurately captures the main features of the SWCC and describes the nonlinear relationship between the matric suction and the water content during wetting and drying processes.
Plain Language Summary
The relationship between the matric suction and the water content in the soil is known as the soil‐water characteristic curve (SWCC). The SWCC is crucial for analyzing the shear strength, deformation, hydraulic conductivity, and aqueous diffusion of unsaturated soils. The drying SWCC is typically located above the wetting SWCC in a given plane. This phenomenon can be described by the hysteretic behavior of the SWCC. The determination of a complete set of hysteretic SWCCs involves measuring the matric suction and water content during wetting and drying processes. However, these measurements are time‐consuming and costly, and the use of raw experimental data without a fitted model is impractical. Therefore, we developed a novel hysteretic model based on the Young‐Laplace equation to address these issues. The model links the physical quantities at the micro‐and macro‐scale and accurately captures the main features of the SWCCs.
Key Points
A hysteretic model considering the contact angle hysteresis is proposed for fitting the main soil‐water characteristic curves based on the Young‐Laplace equation
An evolution of the contact angle during the wetting and drying process is considered
A modified expression between the volume of the liquid bridge and the water content is derived
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