Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson’s disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

A parametric experimental study has been conducted to measure the discharge coefficient, the flow number, the film thickness, the spray angle, the velocity coefficient and droplet size of a large-scale simplex nozzle using ultrasonic and optical techniques. Seventeen nozzle geometries have been studied for three mass flow rates. The large-scale nozzle provides adequate resolution for measurements of film thickness, spray angle, and droplet size. The experimental data collected have been used to derive new and improved correlations for nozzle flow and breakup parameters. It is found that the atomizer constant (ratio of total inlet area to product of the swirl chamber and orifice diameter) is the primary parameter affecting the atomizer performance. As the atomizer constant increases, the discharge and velocity coefficients increase and the spray angle decreases.

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A temporal linear stability analysis has been carried out to predict the instability of a viscous liquid jet surrounded by a swirling air stream with three-dimensional disturbances. The effects of flow conditions and fluid properties on the instability of the liquid jet are investigated via a parametric study by varying axial Weber number axial velocity ratio of the gas to liquid phase, swirl Weber numbers, density ratio and the Ohnesorge number. It is observed that the relative axial velocity between the liquid and gas phases promotes the interfacial instability. As the axial Weber number increases, the growth rates of unstable waves, the most unstable wavenumber and the unstable range of wavenumbers increase. Meanwhile, the increasing importance of helical modes compared to the axisymmetric mode switches the breakup regime from the Rayleigh regime to the first wind-induced regime and on to the second wind-induced regime. The predicted range of wavenumbers in which the first helical mode has higher growth rates than the axisymmetric mode agrees very well with experimental data. Results show that the destabilizing effects of the density ratio and the axial Weber number are nearly the same. Liquid viscosity inhibits the disintegration process of the liquid jet by reducing the growth rate of disturbances and by shifting the most unstable wavenumber to a lower value. Moreover, it damps higher helical modes more significantly than the axisymmetric mode. Air swirl has a stabilizing effect on the liquid jet. As air swirl strength increases, the growth rates of helical modes are reduced more significantly than that of the axisymmetric mode. The air swirl profile is found to have a significant effect on the instability of the liquid jet. The global, as well as local, effects of the swirl profile are examined in detail.

The pressure swirl atomizer, or simplex atomizer, is widely used in liquid fuel combustion devices in the aerospace and power generation industries. A computational, experimental, and theoretical study was conducted to predict its performance. The Arbitrary-Lagrangian-Eulerian method with a finite-volume scheme is employed in the CFD model. Internal flow characteristics of the simplex atomizer, as well as its performance parameters such as discharge coefficient, spray angle and film thickness, are predicted. A temporal linear stability analysis is performed for cylindrical liquid sheets under three-dimensional disturbances. The model incorporates the swirling velocity component, finite film thickness and radius that are essential features of conical liquid sheets emanating from simplex atomizers. It is observed that the relative velocity between the liquid and gas phases, density ratio and surface curvature enhance the interfacial aerodynamic instability. The combination of axial and swirling velocity components is more effective than only the axial component for disintegration of liquid sheet. For both large and small-scale fuel nozzles, mean droplet sizes are predicted based on the linear stability analysis and the proposed breakup model. The predictions agree well with experimental data at both large and small scale.