Objective To investigate the relationship of age-related macular degeneration (AMD) with blood-lipid levels. Methods Individuals 40 years old or older who had undergone a physical-health examination in our hospital between January and December 2017 were enrolled in this study. Information regarding medical history and the results of essential ophthalmological and physical-health examinations were examined to exclude individuals with serious chronic diseases such as malignant tumors, stroke, myocardial infarction, pulmonary heart disease, hypertension, diabetes, and kidney disease. One thousand nine individuals with AMD (all at the early stage) were included in the AMD group, and 3489 individuals without AMD were included in the non-AMD group. Data of all participants, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels, were collected and analyzed. Results The average age in the AMD group was higher than that in the non-AMD group, and the male to female ratio was significantly higher in the AMD group (P<0.05). After adjusting for age, gender, and BMI confounders, multiple linear stepwise regression analysis revealed that HDL-C was associated with AMD (β=-0.026, 95% CI: 0.045-0.006, P=0.011); there was no correlation between TC, TG, LDL-C, and AMD (all P>0.05). Conclusion Early stage AMD was related to a decrease in HDL-C, which may be a protective factor against AMD. Further study is warranted to validate this finding.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.