End-to-End Autonomous Driving Decision Method Based on Improved TD3 Algorithm in Complex Scenarios.

The ability to make informed decisions in complex scenarios is crucial for intelligent automotive systems. Traditional expert rules and other methods often fall short in complex contexts. Recently, reinforcement learning has garnered significant attention due to its superior decision-making capabilities. However, there exists the phenomenon of inaccurate target network estimation, which limits its decision-making ability in complex scenarios. This paper mainly focuses on the study of the underestimation phenomenon, and proposes an end-to-end autonomous driving decision-making method based on an improved TD3 algorithm. This method employs a forward camera to capture data. By introducing a new critic network to form a triple-critic structure and combining it with the target maximization operation, the underestimation problem in the TD3 algorithm is solved. Subsequently, the multi-timestep averaging method is used to address the policy instability caused by the new single critic. In addition, this paper uses Carla platform to construct multi-vehicle unprotected left turn and congested lane-center driving scenarios and verifies the algorithm. The results demonstrate that our method surpasses baseline DDPG and TD3 algorithms in aspects such as convergence speed, estimation accuracy, and policy stability.

Discovery of Highly Selective, Potent, Covalent, and Orally Bioavailable Factor XIIa Inhibitors for the Treatment of Thrombo-Inflammation.

Thrombo-inflammation is closely associated with a few severe cardiovascular and infectious diseases. Factor XIIa (FXIIa) in the intrinsic coagulation pathway plays a pivotal role in the development of thrombo-inflammation and its inhibition has emerged as a potential therapeutic approach for thrombo-inflammatory disorders. Nonetheless, as of now, few small-molecule FXIIa inhibitors have demonstrated notable effectiveness against thrombo-inflammation, with none progressing into clinical stages. Herein, we present potent, covalent, reversible, and selective small-molecule FXIIa inhibitors such as 4a and 4j obtained through structure-based drug design. Compounds 4a and 4j showed significant anticoagulation and substantial anti-inflammatory effects in vitro, coupled with exceptional plasma stability. Furthermore, in carrageenan-induced thrombosis models, 4a and 4j demonstrated remarkable dual antithrombotic and anti-inflammatory activity when administered orally. Compound 4j exhibited a favorable safety profile without obvious tissue toxicity in mice, suggesting its potential as an oral therapeutic option for thrombo-inflammation.

Factor XIa Inhibitors in Anticoagulation Therapy: Recent Advances and Perspectives.

Factor XIa (FXIa) in the intrinsic pathway of the coagulation process has been proven to be an effective and safe target for anticoagulant discovery with limited or no bleeding. Numerous small-molecule FXIa inhibitors (SMFIs) with various scaffolds have been identified in the early stages of drug discovery. They have served as the foundation for the recent discovery of additional promising SMFIs with improved potency, selectivity, and pharmacokinetic profiles, some of which have entered clinical trials for the treatment of thrombosis. After reviewing the coagulation process and structure of FXIa, this perspective discusses the rational or structure-based design, discovery, structure-activity relationships, and development of SMFIs disclosed in recent years. Strategies for identifying more selective and druggable SMFIs are provided, paving the way for the design and discovery of more useful SMFIs for anticoagulation therapy.

Tin (IV) chloride-promoted one-pot synthesis of novel tacrine analogues.

A facile synthesis of potential acetylcholinesterase (AChE) inhibitors, the tacrine analogues 3a-p, has been accomplished by direct cyclocondensation of 1-aryl-4-cyano-5-aminopyrazole with ß-ketoesters using tin(IV) chloride as catalyst. The structures of all the compounds have been confirmed by IR, ¹H- and ¹³C-NMR.