PCSK9 inhibitors ameliorate arterial stiffness in ACS patients: evidences from Mendelian randomization, a retrospective study and basic experiments

BackgroundCurrent evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions.MethodsThis study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group (n = 36, PCSK9 inhibitors combined with statins) and control group (n = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements.ResultsThe results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group (p < 0.05). Additionally, PWV in the PCSK9i group demonstrated significant reduction after 6 months of treatment and was found to be associated with the circulating CRP level. In cell experiments, PCSK9i pretreatment ameliorated osteogenesis of VSMCs through reducing the deposition of calcium ions, alkaline phosphatase (ALP) activity, and expression of runt-related transcription factor 2 (RUNX2).ConclusionPCSK9i have potential to enhance arterial stiffness in ACS patients. Specifically, at the clinical level, this impact may be attributed to alterations in circulating CRP levels. At the cellular level, it is associated with the signaling pathway linked to RUNX2

Analysis of subcarrier multiplexing signals in optical fibre communication

This thesis aims to provide a comprehensive analysis of the nonlinear distortion in SCM optical communication systems. After the basic introduction to subcarrier multiplexed optical communication systems, the three most significant types of nonlinear distortions are analyzed. For each type of nonlinear distortion, an analytical model is presented and verified by numerical simulations and experiments. These analytical models result in many new closed-form expressions. Therefore, the analytical models enable one to get a better physical insight into the nonlinear distortion phenomena and help one to evaluate the impact of these distortions quickly. Hence, these analytical models can facilitate the task of system design greatly. The thesis concludes by mentioning the major conclusions and achievements of the work presented here and the proposed future work.DOCTOR OF PHILOSOPHY (EEE

Miniature Fiber-Optic Magnetic Field Sensor Based on Ampere Force and Fiber Laser

Abstract A compact fiber-optic magnetic field sensor is proposed by packaging an orthogonal dual-frequency fiber grating laser and a copper wire with alternating electrical current together inside epoxy resin. The alternating current generates Ampere force in a magnetic field, which changes the birefringence of the fiber laser and hence tunes the frequency of the beat signal after photodetection. The magnetic field magnitude can then be detected by measuring the frequency change of the beat signal. The sensitivity of the sensor can be tuned with a maximum response of 35.21 kHz/kGs demonstrated. Moreover, the sensor shows good immunity to environment interference

The pattern between nitrogen mineralization and grazing intensities in an Inner Mongolian typical steppe

Abstract Ungulate grazing is known to play a crucial role in regulating energy flow and nutrient cycling in grassland ecosystems. However, previous studies of the effect of grazing on soil N dynamics have showed controversial results. Some studies indicate that grazing stimulates N mineralization while others report that grazing suppresses N mineralization. In order to reconcile these contrasting results, we investigated the response pattern of nitrogen transfor-mation to multiple grazing intensities in an Inner Mongolian steppe. In our study, we measured net nitrogen mineralization rates and nitrification rates during a whole growing season in a 17-year field experiment that had five grazing intensities (0.00, 1.33, 2.67, 4.00 and 5.33 sheep ha−1). Primaril

Brillouin Scattering Spectrum Analysis Based on Auto-Regressive Spectral Estimation

Abstract Auto-regressive (AR) spectral estimation technology is proposed to analyze the Brillouin scattering spectrum in Brillouin optical time-domain refelectometry. It shows that AR based method can reliably estimate the Brillouin frequency shift with an accuracy much better than fast Fourier transform (FFT) based methods provided the data length is not too short. It enables about 3 times improvement over FFT at a moderate spatial resolution