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        Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the “TRPV1-NFATc1-ATF3” pathway and tumor microenvironment engineering

        Jiachen Shi,Qiuling Ma,Wenting Su,Congyan Liu,Huangqin Zhang,Yuping Liu,Xiaoqi Li,Xi Jiang,Chang Ge,Fei Kong,Yan Chen,Ding Qu 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Background Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration. Methods In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@ DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the “one-step micro-molding” method for boosted transdermal and tumoral delivery of cannabidiol (CBD). Results Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@ DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a “one stone, two birds” strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo. Conclusions This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.

      • Perceptual Quality Driven Frame-Rate Selection (PQD-FRS) for High-Frame-Rate Video

        Huang, Qin,Jeong, Se Yoon,Yang, Shanglin,Zhang, Dichen,Hu, Sudeng,Kim, Hui Yong,Choi, Jin Soo,Kuo, C.-C. Jay IEEE 2016 IEEE transactions on broadcasting Vol.62 No.3

        <P>Video of higher frame rates (HFR) reduces the visual artifact in large screen display at the cost of a higher coding bit rate (or transmission bandwidth). In this work, we propose a perceptual quality driven frame rate selection (PQD-FRS) method that assigns a time-varying frame rate to a sequence so as to reduce its transmission cost. The objective of the PQD-FRS method is to offer perceptually indistinguishable experience for a certain percentage of viewers. We first conduct a subjective test to characterize the relationship between human perceived quality and video contents, and build a frame-rate-dependent video quality assessment dataset to serve as the ground truth. Then, we use a machine learning approach for the design of the key module of the PQD-FRS method, called the 'satisfied user ratio (SUR) prediction.' The SUR prediction module predicts the percentage of satisfied viewers, who cannot differentiate video quality of a lower and HFR, using the support vector regression. It is confirmed by experimental results that the proposed SUR module can offer a so highly accurate prediction that the PQD-FRS system can dynamically assign a proper frame rate to video without any perceptual quality degradation for a majority of viewers.</P>

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