Hsp90 Inhibitors(University of Kansas)

Antibiotic resistance genes (ARGs) are a global environmental concern, yet their vertical distribution in pristine marine ecosystems remains poorly understood. This study investigated the distribution of ARG distribution in both the water column and sediments of the Yap Trench, which reaches depths over 6500 m Results revealed significant variations in ARG diversity and abundance across depths and habitats. The deep-water (DW) zones exhibited the highest diversity (291-472 subtypes) and abundance (1.79 copies/cell), followed by upper-water (UW) zones (240-314 subtypes, 0.31 copies/cell), while sediments had the lowest diversity (72-236 subtypes) and abundance (0.03 copies/cell). The most prevalent resistance genes included those conferring resistance to multidrug, polymyxin, and beta-lactam in the Yap Trench. ARG distribution closely correlated with microbial hosts, including Pseudomonadota, Chloroflexota, Bacteroidota, and Planctomycetota. Risk assessment showed high-risk ARGs were most abundant in DW zones, with pathogenic groups capable of spreading multiple ARGs (e.g., macAB, mexDJKW, mdtE, muxC). This study provides a systematic understanding of the distribution patterns and potential risks of ARGs in the water column and sediments of pristine marine ecosystems, underscoring the penetration of antibiotic pollution into the deep ocean and offering new insights for marine pollution control strategies.

The molecular chaperone Heat shock protein 90 (Hsp90), essential for protein homeostasis and cellular stress response, has emerged as a promising therapeutic target across various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. Although numerous Hsp90 inhibitors have been developed and extensively evaluated in clinical studies, progress has been impeded by limited clinical efficacy, narrow therapeutic windows, and challenges in assessing target engagement. These limitations highlight the importance of developing complementary non-invasive molecular imaging tools to better understand Hsp90 function in vivo and optimize therapeutic strategies, including assessing target engagement, refining dosing strategies, monitoring treatment response, and enabling patient stratification. This review provides a comprehensive overview of the current landscape of Hsp90-targeted molecular imaging. We discuss imaging modalities applicable to Hsp90, optical imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET), and highlight key molecular probes developed to visualize Hsp90 expression and function in vivo using these modalities. Furthermore, we summarize significant findings that have deepened our fundamental understanding of Hsp90's role in disease, supported the development of novel therapeutic approaches, demonstrated imaging effectiveness in preclinical models, and suggested potential for integration into clinical research. We also address current challenges and propose future directions for the field. Through this review, we aim to illustrate the translational potential of molecular imaging in advancing our understanding of Hsp90 in disease and optimizing Hsp90-targeted therapeutics, thereby contributing to precision medicine approaches.