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Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s−1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s−1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND Increased reactive oxygen species (ROS) and oxidative stress response lead to cardiomyocyte hypertrophy and apoptosis, which play crucial roles in the pathogenesis of heart failure. The purpose of current research was to explore the role of antioxidant N -acetylcysteine (NAC) on cardiomyocyte dysfunction and the underlying molecular mechanisms. METHODS AND RESULTS Compared with control group without NAC treatment, NAC dramatically inhibited the cell size of primary cultured neonatal rat cardiomyocytes (NRCMs) tested by immunofluorescence staining and reduced the expression of representative markers associated with hypertrophic, fibrosis and apoptosis subjected to phenylephrine administration examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Moreover, enhanced ROS expression was attenuated, whereas activities of makers related to oxidative stress response examined by individual assay Kits, including total antioxidation capacity (T-AOC), glutathione peroxidase (GSH-Px), and primary antioxidant enzyme Superoxide dismutase (SOD) were induced by NAC treatment in NRCMs previously treated with phenylephrine. Mechanistically, we noticed that the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and AKT were increased by NAC stimulation. More importantly, we identified that the negative regulation of NAC in cardiomyocyte dysfunction was contributed by PI3K/AKT signaling pathway through further utilization of PI3K/AKT inhibitor (LY294002) or agonist (SC79). CONCLUSIONS Collected, NAC could attenuate cardiomyocyte dysfunction subjected to phenylephrine, partially by regulating the ROS-induced PI3K/AKT-dependent signaling pathway. [ABSTRACT FROM AUTHOR]

Background P21-activated kinase 1 (Pak1) has an effect on cell apoptosis and has recently been reported to play an important role in various cardiovascular diseases, in which vascular smooth muscle cell (VSMC) apoptosis is a key process. Thus, we hypothesized that Pak1 may be a novel target to regulate VSMC behaviors. Methods and Results In the present study, we found that the expression of Pak1 was dramatically upregulated in vascular smooth muscle cells (VSMCs) on H2O2 administration and was dependent on stimulation time. Through a loss-of-function approach, Pak1 knockdown increased apoptosis of VSMCs, as tested by TUNEL (TdT-mediated dUTP Nick-End Labeling) immunofluorescence staining, whereas it inhibited the proliferation of VSMCs examined by EdU staining. Moreover, we also noticed that Pak1 silencing promoted the mRNA and protein levels of pro-apoptosis genes but decreased anti-apoptosis marker expression. Importantly, we showed that Pak1 knockdown reduced the phosphorylation of Bad. Moreover, increased Pak1 expression was also noticed in carotid arteries on the wire jury. Conclusions Our study identified that Pak1 acted as a novel regulator of apoptosis of VSMCs partially through phosphorylation of Bad. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the postactivation performance enhancement (PAPE) effects of medicine ball throwing (MBT) and bench pressing (BP) on punching impact at different recovery times. Methods: Fourteen amateur boxers performed three lead-hand (lead-hand) and rear-hand straight punches (rear-hand) at 3, 6, 9, 12, and 15 min after MBT or BP exercise. Peak force, time to the peak force, and rate of force development (RFD) of each punch was measured by a force plate. Results: There was no significant condition × time interaction effect for any variables (lead-hand: F = 0.744–0.913, p = 0.448–0.542; rear-hand: F = 0.240–1.355, p = 0.245–0.944). No significant main effect for condition for any variables (lead-hand: F = 0.103–0.219, p = 0.644–0.751; rear-hand: F = 0.070–0.459, p = 0.504–0.793). The time effect was significant on peak force (F = 4.411, p = 0.005) and RFD (F = 5.002, p = 0.002) of lead-hand, time to the peak force (F = 5.791, p = 0.001) and RFD (F = 5.514, p = 0.001) of rear-hand. Peak force and RFD of the lead-hand, as well as time to the peak force and RFD of the rear-hand enhanced significantly at 6–15 min (p = 0.001–0.042), compared to the baseline. Conclusions: MBT and BP may equally enhance punching impact for amateur boxers; moreover, there was no difference in recovery time between conditioning activities. [ABSTRACT FROM AUTHOR]

We agree that smoking might be a risk factor for the severity of COVID‐19, but in our previous study, smoking was not so robust compared with our conclusion. Also, we strongly agreed that COVID‐19 patients with diabetes or other chronic diseases might worsen the situation of the disease. But these factors were out of the scope of our study and we had published other research on this topic related to diabetes. Because of the limited sample size and original medical records, our study could not cover many factors. But we wish our study will be a useful and meaningful pilot study for future studies. [ABSTRACT FROM AUTHOR]