| 2 | Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation ofβ-catenin显示文摘Vestibular schwannoma(VS),one of characteristic tumors of neurofibromatosis type 2(NF2),is an intracranial tumor that arises from Schwann cells of the vestibular nerve.VS results in hearing loss,tinnitus,dizziness,and even death,but there are currently no FDA-approved drugs for treatment.In this study,we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells.Among 1019 natural products from the Korea Chemical Bank screened,we found that celastrol,a pentacyclic triterpene derived from a Tripterygium Wilfordi plant,exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5µM.Celastrol(0.5,1µM)dose-dependently inhibited the proliferation of primary VS cells derived from VS patients.Celastrol also inhibited the growth,and induced apoptosis of two other VS cell lines(HEI-193 and SC4).Aberrant activation of Wnt/β-catenin signaling has been found in VS isolated from clinically defined NF2 patients.In HEI-193 and SC4 cells,we demonstrated that celastrol(0.1,0.5μM)dose-dependently inhibited TOPFlash reporter activity and protein expression ofβ-catenin,but not mRNA level ofβ-catenin.Furthermore,celastrol accelerated the degradation ofβ-catenin by promoting the formation of theβ-catenin destruction complex.In nude mice bearing VS cell line SC4 allografts,administration of celastrol(1.25 mg·kg^(−1)·d^(−1),i.p.once every 3 days for 2 weeks)significantly suppressed the tumor growth without showing toxicity.Collectively,this study demonstrates that celastrol can inhibit Wnt/β-catenin signaling by promoting the degradation ofβ-catenin,consequently inhibiting the growth of VS. | Na Hui Kim Minji Kwon Jiwoo Jung Hyo Byeong Chae Jiwoo Lee Yeo-Jun Yoon In Seok Moon Ho KLee Wan Namkung Konstantina M.Stankovic Se A.Lee Jong Dae Lee Sin-Aye Park | 2022 | Acta Pharmacologica Sinica2022，43，11： | 0 |
| 3 | Inhomogeneous lithium-storage reaction triggering the inefficiency of all-solid-state batteries显示文摘All-solid-state batteries offer an attractive option for developing safe lithium-ion batteries.Among the various solid-state electrolyte candidates for their applications,sulfide solid electrolytes are the most suitable owing to their high ionic conductivity and facile processability.However,their performance is extensively lower compared with those of conventional liquid electrolyte-based batteries mainly because of interfacial reactions between the solid electrolytes and high capacity cathodes.Moreover,the kinetic evolution reaction in the composite cathode of all-solid-state lithium batteries has not been actively discussed.Here,electrochemical analyses were performed to investigate the differences between the organic liquid electrolyte-based battery and all-solid-state battery systems.Combined with electrochemical analyses and synchrotron-based in situ and ex situ X-ray analyses,it was confirmed that inhomogeneous reactions were due to physical contact.Loosely contacted and/or isolated active material particles account for the inhomogeneously charged regions,which further intensify the inhomogeneous reactions during extended cycles,thereby increasing the polarization of the system.This study highlighted the benefits of electrochemo-mechanical integrity for securing a smooth conduction pathway and the development of a reliable homogeneous reaction system for the success of solid-state batteries. | Jaeyoung Kim Wontae Lee Jangwhan Seok Eunkang Lee Woosung Choi Hyunyoung Park Soyeong Yun Minji Kim Jun Lim Won-Sub Yoon | 2022 | Journal of Energy Chemistry2022，31，3： | 0 |
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