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Median filtering forensics has attracted much attention in recent years. However, most existing methods exploit either spatial domain or frequency domain features, while neglect the correlation between them. Moreover, they often suffer from inadequate generalization in cross-database and cross-parameter. To solve these problems, we propose an attention-based dual-domain fusion network (DDFNet) to fuse spatial domain and frequency domain features in a mutually complementary way. In the spatial domain, we use four types of modules aimed at extracting the pixel residual features. In the frequency domain, the discrete cosine transform (DCT) coefficients are fed into a residual network to capture the frequency residual features. Finally, the features obtained from the two domains are fused by an attention module to mine their latent complementary relationships. Extensive experiments demonstrate that the proposed DDFNet outperforms the state-of-the-art methods in terms of robustness and generalization capacity.

Surface-modified mesoporous silica nanoparticles (MSNs) have attracted more and more attention as promising materials for biomolecule delivery. However, the lack of detailed evaluation relevant to the potential cytotoxicity of these MSNs is still a major obstacle for their applications. Unlike the bare MSNs and amino- or liposome-modified MSNs, we found that polyethylenimine-modified MSNs (MSNs-PEI) had no obvious toxicity to human umbilical vein endothelial cells (HUVECs) at the concentrations up to 100 μg/mL. However, MSNs-PEI induced autophagosomes accumulation by blocking their fusion with lysosomes, an essential mechanism for the cytotoxicity of many nanoparticles (NPs). Thus, we predicted that an alternative pathway for autophagosome clearance exists in HUVECs to relieve autophagic stress induced by MSNs-PEI. We found that MSNs-PEI prevented STX17 loading onto autophagosomes instead of influencing lysosomal pH or proteolytic activity. MSNs-PEI induced the structural alternation of the cytoskeleton but did not cause endoplasmic reticulum stress. The accumulated autophagosomes were released to the extracellular space viamicrovesicles (MVs) when the autophagic degradation was blocked by MSNs-PEI. More importantly, blockade of either autophagosome formation or release caused the accumulation of damaged mitochondria and excessive ROS production in the MSNs-PEI-treated HUVECs, which in turn led to cell death. Thus, we propose here that the MV-mediated autophagosome release, a compensation mechanism, allows the vascular endothelial cell survival when the degradation of autophagosomes is blocked by MSNs-PEI. Accordingly, promoting the release of accumulated autophagosomes may be a protective strategy against the endothelial toxicity of NPs.

Coenzyme Q10 (CoQ10) has a wide range of nutraceutical functions and therapeutic values, nevertheless, its biomedical application as a health product or drug is hampered by the low absorption efficiency and bioavailability. In the present study, the hybrid mesoporous silica nanoparticle-supported lipid bilayers (LMSNs) as nanocarriers for CoQ10 are prepared by fusing the phospholipid membrane onto MSNs cores. Further, LMSNs are functionalized with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), deoxycholic acid (Doca) and chitosan (CS) sequentially, to obtain the TPGS-LMSNs and DCs-TPGS-LMSNs samples, respectively. MSNs, liposomes, and unmodified LMSNs are also prepared as controls. The results reveal that various nanocarriers have a high loading capacity for CoQ10, low cytotoxicity towards Caco-2 cells, and sustained release property in different pH mediums. In contrast to other nano-formulations, DC-TPGS-LMSNs@CoQ10 show the higher cellular uptake efficiency and the resulting ROS inhibition effect, which can be taken up by cells via caveolae-mediated route, macropinocytosis, and unique bile acid uptake pathway mediated by ASBT. Efficient delivery of DC-TPGS-LMSNs is further illustrated by in vivointestinal uptake and pharmacokinetics study, in which DC-TPGS-LMSNs@CoQ10 exhibit higher absorption efficiency, longer circulation time, and more enhanced bioavailability than other formulations after oral administration. The results suggest that multifunctional LMSNs might be the potent candidate for CoQ10 delivery, and the findings will contribute to the rational design of novel drug delivery vehicles.