Sookmyung Women's University

p21-Activated kinase 4 (PAK4) is a Group II serine/threonine kinase implicated in tumor growth and immune evasion, and is therefore a promising target for anticancer therapy. Leveraging structure-guided design, we report a novel series of 6-aminopyridine derivatives that target a previously underexplored deep hydrophobic subpocket adjacent to Phe461, which extends from the floor pocket of PAK4. Even with a relatively concise compound set, the focused SAR study identified key substituent features required for deep-pocket engagement, and subsequent molecular docking and dynamics simulations supported an underexploited binding mode centered on the key residue Phe461. Among the synthesized compounds, 17 (PAK4 IC₅₀ 0.71 μM) and 29 (PAK4 IC₅₀ 1.88 μM) demonstrated comparable enzymatic potency, consistent with ATP-competitive inhibition, while compound 29 was effective in inhibiting cancer cell proliferation (HCT-116 GI₅₀ 23.0 μM; A549 GI₅₀ 11.3 μM). In conclusion, this study highlights the potential of targeting underexplored subpockets in PAK4 and provides new molecular insights for the discovery of PAK4 inhibitors.

van der Waals (vdW) layered semiconductors have emerged as a unique class of quantum materials distinguished from their bulk counterparts by reduced dielectric screening, strong Coulomb interactions, large exciton binding energies, strong spin-orbit coupling, and pronounced thickness-dependent band structures. These fundamental attributes have enabled the exploration of exotic many-body physics and a broad spectrum of device applications, ranging from field-effect transistors and ferroelectric switches to optoelectronics, magnetic semiconductors, neuromorphic computing, and energy harvesting systems. Despite remarkable advances, critical challenges remain in the controlled synthesis of high-quality crystals, formation of low-resistance contacts, integration of stable and scalable gate dielectrics, and reliable device performance at the wafer scale. In this mega-review, we provide a comprehensive overview of contemporary challenges and future opportunities in vdW-layered semiconductors, structured across nine themes: growth and heterostructures of transition metal dichalcogenides, Ohmic contacts, emerging gate dielectrics, high-performance low-power field-effect transistors (FETs), diluted magnetic semiconductors, plasmonics and exciton propagation, hot-carrier solar cells, bioinspired neuromorphic computing, and electrocatalytic/photocatalytic energy conversion. By consolidating fundamental insights and device-level perspectives, this review aims to chart a roadmap for advancing vdW semiconductors from laboratory-scale discoveries to transformative technologies in electronics, optoelectronics, spintronics, and sustainable energy systems.

Background: The intake of red or processed meat remains controversial as a crucial factor for CRC. Thus, we performed in-depth biological monitoring. Methods: We performed a case- control study and analyzed various exposure and response biomarkers including 1-OHP, MeIQx, and PhIP, and malondialdehyde (MDA), and heterocyclic amine (HCA)-DNA adducts in Korean cases and controls (N = 218). Results: They consumed 53.4 ± 74.0 g/day of red meat and 1.1 ± 3.7 g/day of processed meat. The CRC presence was associated with sex, BMI, tobacco smoking, alcohol drinking, cooking method of meat, and vegetable consumption, rather than red or processed meat intake. The levels of MDA were positively associated with those of 1-OHP, MeIQx, or PhIP. The sum of 1-OHP, MeIQx, and PhIP was associated with the levels of HCA-DNA adducts and cooking method of meat. In addition, the above biomarkers for CRC were associated with each other. However, most of these biomarkers were not higher in CRC patients than those in controls. Conclusion: The present in-depth biological monitoring provides that red or processed meat may induce oxidative stress; however, present intake of the meat and the intake-related oxidative stress may not affect CRC prevalence among the Korean population, who consume less meat than Westerners.