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In this study, a pH-responsive nano-prodrug was fabricated by conjugating emodin to the PEGylated polyethyleneimine (mPEG-PEI) with acid-sensitive boronate ester bonds. 1H NMR spectra results showed that emodin was effectively bonded to mPEG-PEI, and acid-sensitive assay further confirmed the formation of boronate ester bonds. The size and morphology of the nano-prodrug were ascertained through transmission electron microscopy (TEM) and dynamic light scattering (DLS), which showed that the prodrug has a sphere-like shape with hydrodynamic size around 102 nm at pH 7.4. Subsequently, a drug-release behavior assay was carried out to carefully investigate the acid-sensitive drug-delivery property of the prodrug. Moreover, in vitro cell viability assay confirmed the superior cytotoxic effect of the nano-prodrug against HeLa cells compared to free emodin. Furthermore, the antibacterial study showed that the nano-prodrug could inhibit the bacterial (both Gram-positive and Gram-negative) growth more effectively than free emodin. Overall, this study provides a promising paradigm of the multifunctional nano-prodrug for pH-responsive tumor therapy and antibacterial activity.

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Background: Black-blood thrombus imaging (BTI) has shown to be advantageous for the diagnosis of deep vein thrombosis (DVT). However, previous techniques using fast spin echo have a high specific absorption rate. As DANTE (delay alternating with nutation for tailored excitation) black-blood preparation can suppress blood flows over a broad range of velocities, we hypothesized that a DANTE black-blood preparation combined with a fast low-angle shot (FLASH) gradient-echo readout-DANTE-FLASH could be used to diagnose DVT.Methods: Eleven healthy volunteers and 30 suspected DVT patients were recruited to undergo DANTE-FLASH and magnetic resonance direct thrombus imaging (MRDTI). The suspected DVT patients were also examined by ultrasound (US). For the segment level, a total of 1,066 venous vessel segments were analyzed.Using US and MRDTI as the references, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of DANTE-FLASH were calculated. To quantitatively compare image quality between DANTE-FLASH and MRDTI, image signal-to-noise ratio (SNR), apparent contrastto-noise ratio (CNR) between muscle and the venous lumen, and the apparent CNR between the thrombus and venous lumen were measured. Additionally, diagnostic confidence, image quality, and clot burden were also evaluated.Results: Using the consensus results of US and MRDTI as a standard reference, the diagnostic SE, SP, PPV, NPV, and ACC of DANTE-FLASH for the 2 readers were 97.0% and 93.2%, 99.0% and 98.2%, 93.4% and 87.9%, 99.6% and 99.0%, and 98.8% and 97.6%, respectively. According to the image quantitative analysis results, DANTE-FLASH demonstrated higher image SNR and CNR than MRDTI.The image quality and diagnostic confidence scores of DANTE-FLASH were higher than MRDTI (3.66±0.44 vs. 3.52±0.52, P<0.001, and 3.84±0.36 vs. 3.76±0.41, P<0.001). There was excellent agreement between DANTE-FLASH and MRDTI on clot burden evaluation.Conclusions: DANTE-FLASH provided better image quality than MRDTI and accurately detected thrombi. It may, therefore, serve as a safe and convenient alternative for the diagnosis of DVT.