Association between the variability of non-high-density lipoprotein cholesterol and the neutrophil-to-lymphocyte ratio in patients with coronary heart disease

BackgroundLowering lipid variability may be a potential strategy for improving the inflammatory state in patients with coronary heart disease (CHD). This study investigated the association between the variability of non-high-density lipoprotein cholesterol (non-HDL-C) and the neutrophil-to-lymphocyte ratio (NLR).MethodsThis study enrolled 2,711 CHD patients subjected to percutaneous coronary intervention (PCI). During the 1-year follow-up period after PCI, the variability of non-HDL-C was assessed using standard deviation (SD), coefficient of variation (CV), and variability independent of mean (VIM). NLR was calculated as the ratio of absolute neutrophil count to absolute lymphocyte count. The relationship between the non-HDL-C variability and the average NLR level during follow-ups was examined using a linear regression analysis.ResultsThe mean age of the patients was 64.4 ± 10.8 years, with 72.4% being male. The average NLR level was 2.98 (2.26–4.14) during the follow-up (1 year after PCI). The variability of non-HDL-C was 0.42 (0.26–0.67) for SD, 0.17 (0.11–0.25) for CV, and 0.02 (0.01–0.03) for VIM. A locally weighted scatterplot smoothing curve indicates that the average levels of NLR increased with increasing variability of non-HDL-C. Regardless of the variability assessment method used, non-HDL-C variability was significantly positively associated with the average NLR level during follow-ups: SD [β (95% CI) = 0.681 (0.366–0.996)], CV [β (95% CI) = 2.328 (1.458–3.197)], and VIM [β (95% CI) = 17.124 (10.532–23.715)]. This association remained consistent across subgroups stratified by age, gender, diabetes, and hypertension.ConclusionThe variability of non-HDL-C was positively associated with NLR in patients with CHD, suggesting that reducing non-HDL-C variability may improve the low-grade inflammatory state in CHD patients

Mechanical Properties of Natural Rubber Filled with Foundry Waste Derived Fillers

The main aim of this study is to evaluate the possibility of applying foundry dust (FD) derived filler for the preparation of natural rubber (NR) based composites by characterizing the mechanical properties. The as-received FD was processed via a simple and low-cost procedure, including sieving, deironing and milling using a variety of industrial equipment. FD powders before and after silane coupling agent (Si 69) modification were used as fillers for NR. NR composites inserted with different content of modified and unmodified FD up to 50 phr were prepared via dry-mixing method. Then, comprehensive mechanical performances were performed on the corresponding vulcanizates. It was demonstrated that NR composite filled with 50 phr of modified FD exhibited optimized comprehensive mechanical performance. Tear strength and hardness is increased by 21.3% and 12.8% than pure NR, respectively. Tensile strength is reduced by 21% and elongation at break remained nearly unchanged. Additionally, the composite showed a large increment of 50.9% for its wet grip property, while exhibited an increment of only 11.9% for its rolling resistance in comparison with the composite containing 10 phr of FD. The findings of this study may provide a new application area for the large amounts of utilization of foundry waste with a high level of value being added

An episomal vector-based CRISPR/Cas9 system for highly efficient gene knockout in human pluripotent stem cells

Abstract Human pluripotent stem cells (hPSCs) represent a unique opportunity for understanding the molecular mechanisms underlying complex traits and diseases. CRISPR/Cas9 is a powerful tool to introduce genetic mutations into the hPSCs for loss-of-function studies. Here, we developed an episomal vector-based CRISPR/Cas9 system, which we called epiCRISPR, for highly efficient gene knockout in hPSCs. The epiCRISPR system enables generation of up to 100% Insertion/Deletion (indel) rates. In addition, the epiCRISPR system enables efficient double-gene knockout and genomic deletion. To minimize off-target cleavage, we combined the episomal vector technology with double-nicking strategy and recent developed high fidelity Cas9. Thus the epiCRISPR system offers a highly efficient platform for genetic analysis in hPSCs

Efficacy of Mobile-Based Cognitive Behavioral Therapy on Lowering Low-density Lipoprotein Cholesterol Levels in Patients With Atherosclerotic Cardiovascular Disease: Multicenter, Prospective Randomized Controlled Trial

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. ObjectiveThis trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. MethodsThis multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: “CBT ASCVD.” The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (<1.8 mmol/L) at the first, third, and sixth months. ResultsFinally, 296 participants completed the 6-month follow-up (CBT group: n=148; control group: n=148). At baseline, the mean LDL-C level was 2.48 (SD 0.90) mmol/L, and the LDL-C up-to-standard rate (<1.8 mmol/L) was 21.3%. Mobile-based CBT intervention significantly increased the reduction of LDL-C change (%) at the 6-month follow-up (β=–10.026, 95% CI –18.111 to –1.940). In addition, this benefit remained when baseline LDL-C <1.8 mmol/L (β=–24.103, 95% CI –43.110 to –5.095). Logistic regression analysis showed that mobile-based CBT intervention moderately increased the LDL-C up-to-standard rates (<1.8 mmol/L) in the sixth month (odds ratio 1.579, 95% CI 0.994-2.508). For GSE and QL-index, mobile-based CBT intervention significantly increased the change of scores (%) at the 1-, 3-, and 6-month follow-up (all P values <.05). ConclusionsIn patients with ASCVD, mobile-based CBT is effective in reducing LDL-C levels (even for those who already had a standard LDL-C) and can improve self-efficacy and quality of life. Trial RegistrationChinese Clinical Trial Registry ChiCTR2100046775; https://www.chictr.org.cn/showproj.aspx?proj=12714

TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice

Tumor progression locus 2 (TPL2) (MAP3K8) is a central signaling node in the inflammatory response of peripheral immune cells. We find that TPL2 kinase activity modulates microglial cytokine release and is required for microglia-mediated neuron death in vitro. In acute in vivo neuroinflammation settings, TPL2 kinase activity regulates microglia activation states and brain cytokine levels. In a tauopathy model of chronic neurodegeneration, loss of TPL2 kinase activity reduces neuroinflammation and rescues synapse loss, brain volume loss, and behavioral deficits. Single-cell RNA sequencing analysis indicates that protection in the tauopathy model was associated with reductions in activated microglia subpopulations as well as infiltrating peripheral immune cells. Overall, using various models, we find that TPL2 kinase activity can promote multiple harmful consequences of microglial activation in the brain including cytokine release, iNOS (inducible nitric oxide synthase) induction, astrocyte activation, and immune cell infiltration. Consequently, inhibiting TPL2 kinase activity could represent a potential therapeutic strategy in neurodegenerative conditions