Design strategies and recent development of bioactive modulators for glutamine transporters.

Glutamine transporters are integral to the metabolism of glutamine in both healthy tissues and cancerous cells, playing a pivotal role in maintaining amino acid balance, synthesizing biomolecules, and regulating redox equilibrium. Their critical functions in cellular metabolism make them promising targets for oncological therapies. Recent years have witnessed substantial progress in the field of glutamine transporters, marked by breakthroughs in understanding of their protein structures and the discovery of novel inhibitors, prodrugs, and radiotracers. This review provides a comprehensive update on the latest advancements in modulators targeting the glutamine transporter, with special attention given to LAT1 and ASCT2. It also discusses innovative approaches in drug design aimed at these transporters.

Dual-target Janus kinase (JAK) inhibitors: Comprehensive review on the JAK-based strategies for treating solid or hematological malignancies and immune-related diseases.

Janus kinases (JAKs) are the non-receptor tyrosine kinases covering JAK1, JAK2, JAK3, and TYK2 which regulate signal transductions of hematopoietic cytokines and growth factors to play essential roles in cell growth, survival, and development. Dysregulated JAK activity leading to a constitutively activated signal transducers and activators of transcription (STAT) is strongly associated with immune-related diseases and cancers. Targeting JAK to interfere the signaling of JAK/STAT pathway has achieved quite success in the treatment of these diseases. However, inadequate clinical response and serious adverse events come along by the treatment of monotherapy of JAK inhibitors. With better and deeper understanding of JAK/STAT pathway in the pathogenesis of diseases, researchers start to show huge interest in combining inhibition of JAK and other oncogenic targets to realize a broader regulation on pathological processes to block disease development and progression, which has hastened extensive research of dual JAK inhibitors over the past decades. Until now, studies of dual JAK inhibitors have added BTK, SYK, FLT3, HDAC, Src, and Aurora kinases to the overall inhibitory profile and demonstrated significant advantage and superiority over single-target inhibitors. In this review, we elucidated the possible mechanism of synergic effects caused by dual JAK inhibitors and briefly describe the development of these agents.

Research on Modern Marine Environmental Governance in China: Subject Identification, Structural Characteristics, and Operational Mechanisms.

Under the guidance of modern environmental governance concepts, there have been profound changes in the subject, structure, and operational mechanism of the modern marine environmental governance in China. This paper first classifies the subjects of modern marine environmental governance in China, as well as their relationships; analyses the structural characteristics from the three levels of rights, society, and region; explores the operational mechanism; and builds the framework of the modern marine environmental governance system in China. Both the central and local governments act as the leaders of the modern marine environmental governance system in China, and there have been many new changes in their relationships. On the one hand, the interest and goals of the central and local governments have gradually converged under the pressure system. On the other hand, local governments follow the principles of comprehensive governance regarding the coastline and collaborative cooperation is gradually beginning to occur. Different governance subjects are interrelated and intertwined to form a complete modern marine environmental governance structure, which includes the following three levels: the governmental power structure; the social structure, which involves collaboration between multiple entities; and the regional structure, which involves land-sea coordination in environmental governance. These structures each play their parts in the overall process of the marine environmental governance's institutional arrangements, process coordination, and feedback adjustments and ultimately constitute a dynamic and complete modern marine environmental governance operational system.