A combination of excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) has opened new opportunities to develop color-tunable luminescent materials with high quantum yield. Understanding the emission mechanism of these luminophores is essential for the molecular design and construction of a functional system. Herein, we report QM (MS-CASPT2// TD-DFT, MS-CASPT2//CASSCF) and ONIOM (QM/ MM) studies on the fluorescence quenching and AIE mechanisms of 2-(2-hydroxy-phenyl)-4(3H)-quinazolinone with typical characteristics of AIE and ESIPT as an example. The computational results indicate that in the tetrahydrofuran solution, once being excited to the S 1 state, the molecule tends to undergo an ultrafast, barrierless ESIPT from enol to keto tautomer and then accesses a S 1 /S 0 conical intersection in the vicinity of a CC bond twisted intramolecular charge-transfer (TICT) intermediate, leading to a nonradiative decay from the excited to ground state. Hence, the TICT-induced nonadiabatic transition, which has been further confirmed by the on-the-fly trajectory surface hopping dynamics simulations, accounts for the fluorescence quenching in solution. In contrast, in the solid state, the nonradiative relaxation pathway via the CC bond rotation is suppressed due to environmental hindrance, leaving the ESIPT-induced enol−keto tautomerization as the only excited-decay channel, thus the fluorescence is observably enhanced in the crystal.

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Rho‐associated coiled‐coil kinase 1 (ROCK1) is proposed to be implicated in Aβ suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aβ was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased β‐secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y‐27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.

Magnetic resonance imaging (MRI) is currently considered the gold standard for assessing hemophilic arthropathy (HA) severity; however, MRI is often costly, time-consuming, and difficult to perform in children. In the present study, we evaluated the joint status of hemophilic patients from Shanxi Province, China, using musculoskeletal ultrasonography (MSKUS) and identified the factors that most strongly correlated with disease severity.The study included 104 patients with hemophilia, who underwent MSKUS examination. A total of 1248 joints (including the shoulder, elbow, wrist, hip, knee, and ankle joints on both sides) from these patients were evaluated. Effusion, hypertrophy, cartilage modification, and bone erosion were assessed. The chi-square test was used to analyze categorical variables, and multivariate logistic regression was used to analyze the relationship between joint disease and risk factors.MSKUS allowed clear visualization of synovial lesions, effusion, cartilage modification, and bone surface damage; however, it was unable to identify changes deep within bones. The distribution of damaged joints was as follows: shoulder, 2 (1.0%); elbow, 80 (38.5%); wrist, 4 (1.9%); hip, 4 (1.9%); knee, 126 (60.6%); and ankle, 90 (43.3%). Damage was more common in the knee, elbow, and ankle joints than in the shoulder, wrist, and hip joints (P < .001). Among the 1248 joints, 306 showed lesions, which included effusion in 102 (8.2%) joints, synovium hypertrophy in 176 (14.1%), cartilage modification in 193 (15.5%), and bone damage in 176 (14.1%). Many joints had multiple lesions at the same time. The chi-square test and multivariate logistic analysis showed that age and hemophilia severity were significantly associated with joint disease, while type of hemophilia and treatment categories were not associated with joint disease.MSKUS is a convenient and cost-effective examination that can play an important role in the diagnosis and long-term monitoring of HA.