A Self-Delivery Nanodrug Simultaneously Inhibits COX-2/PGE2 Mediated Inflammation and Downregulates PD-L1 to Boost Photoimmunotherapy.

Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.

Morphological Changes of Amygdala in Turner Syndrome Patients.

AIMS: Turner's syndrome (TS) losts one of the X chromosomes and exhibits social cognition deficits. Previous studies have reported that women with TS demonstrated structural and functional abnormalities in brain, including increased volume in amygdala. However, most studies regarded the amygdala as a whole, and the abnormalities in the specific subregions of amygdala in TS have not been studied. Here, we aimed to investigate the local morphological changes of amygdala in TS using the surface morphology analysis method. METHODS: A total of 19 adolescents with 45XO TS and 20 matched adolescents with typical development were evaluated using magnetic resonance imaging. The amygdalae of all participants were manually delineated. 3D surface remodeling and parameterization were performed based on the outlined boundaries of amygdalae. We extracted two surface metrics, namely direct Euclidean displacement and normal projection that were used to represent the morphology of amygdala. RESULTS: Statistical analysis showed significant outward deformation in the laterobasal subregion of left amygdala in patients with TS, compared with the controls using either direct Euclidean displacement or normal displacement. CONCLUSIONS: Our findings provide novel insight into the pathological changes in the amygdala of patients with TS.