Roles of reconstituted high-density lipoprotein nanoparticles in cardiovascular disease: A new paradigm for drug discovery

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear

Balance, Imbalance, and Rebalance: Understanding Robust Overfitting from a Minimax Game Perspective

Adversarial Training (AT) has become arguably the state-of-the-art algorithm for extracting robust features. However, researchers recently notice that AT suffers from severe robust overfitting problems, particularly after learning rate (LR) decay. In this paper, we explain this phenomenon by viewing adversarial training as a dynamic minimax game between the model trainer and the attacker. Specifically, we analyze how LR decay breaks the balance between the minimax game by empowering the trainer with a stronger memorization ability, and show such imbalance induces robust overfitting as a result of memorizing non-robust features. We validate this understanding with extensive experiments, and provide a holistic view of robust overfitting from the dynamics of both the two game players. This understanding further inspires us to alleviate robust overfitting by rebalancing the two players by either regularizing the trainer's capacity or improving the attack strength. Experiments show that the proposed ReBalanced Adversarial Training (ReBAT) can attain good robustness and does not suffer from robust overfitting even after very long training. Code is available at https://github.com/PKU-ML/ReBAT.Comment: Accepted by NeurIPS 202

Determination of fundamental properties of an M31 globular cluster from main-sequence photometry

M31 globular cluster B379 is the first extragalactic cluster, the age of which was determined by main-sequence photometry. In this method, the age of a cluster is obtained by fitting its CMD with stellar evolutionary models. However, different stellar evolutionary models use different parameters of stellar evolution, such as range of stellar masses, different opacities and equations of state, and different recipes, and so on. So, it is interesting to check whether different stellar evolutionary models can give consistent results for the same cluster. Brown et al. (2004a) constrained the age of B379 by comparing its CMD with isochrones of the 2006 VandenBerg models. Using SSP models of BC03 and its multi-photometry, Ma et al. (2007) independently determined the age of B379, which is in good agreement with the determination of Brown et al. (2004a). The BC03 models are calculated based on the Padova evolutionary tracks. It is necessary to check whether the age of B379 which, being determined based on the Padova evolutionary tracks, is in agreement with the determination of Brown et al. (2004a). So, in this paper, we re-determine its age using isochrones of the Padova stellar evolutionary models. In addition, the metal abundance, the distance modulus, and the reddening value for B379 are also determined in this paper. The results obtained in this paper are consistent with the previous determinations, which including the age obtained by Brown et al. (2004a). So, this paper confirms the consistence of the age scale of B379 between the Padova isochrones and the 2006 VandenBerg isochrones, i.e. the results' comparison between Brown et al. (2004a) and Ma et al. (2007) is meaningful. The results obtained in this paper are: the metallicity [M/H]=-0.325, the age $\tau=11.0\pm1.5$ Gyr, the reddening value E(B-V)=0.08, and the distance modulus $(m-M)_{0}=24.44\pm0.10$.Comment: Accepted for Publication in PASP, 7 pages, 1 figure and 1 tabl