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Uniform embedding was first introduced in 2012 for non-side-informed JPEG steganography, and then extended to the side-informed JPEG steganography in 2014. The idea behind uniform embedding is that, by uniformly spreading the embedding modifications to the quantized discrete cosine transform (DCT) coefficients of all possible magnitudes, the average changes of the first-order and the second-order statistics can be possibly minimized, which leads to less statistical detectability. The purpose of this paper is to refine the uniform embedding by considering the relative changes of statistical model for digital images, aiming to make the embedding modifications to be proportional to the coefficient of variation. Such a new strategy can be regarded as generalized uniform embedding in substantial sense. Compared with the original uniform embedding distortion (UED), the proposed method uses all the DCT coefficients (including the DC, zero, and non-zero AC coefficients) as the cover elements. We call the corresponding distortion function uniform embedding revisited distortion (UERD), which incorporates the complexities of both the DCT block and the DCT mode of each DCT coefficient (i.e., selection channel), and can be directly derived from the DCT domain. The effectiveness of the proposed scheme is verified with the evidence obtained from the exhaustive experiments using a popular steganalyzer with rich models on the BOSSbase database. The proposed UERD gains a significant performance improvement in terms of secure embedding capacity when compared with the original UED, and rivals the current state-of-the-art with much reduced computational complexity.

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681–4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC.

Numerous applications of polyethylene glycol derived polymers (PEGs) have been reported in the scientific literature for many years. With increasing experience and comfort by regulatory authorities, worldwide, in the utilization of these materials in drug and medical device applications, their use in a variety of research and development areas is expanding. This review will focus on just the range of applications of PEGs published in the first half of 2014 in the medical device, drug development, and diagnostics areas, including drug delivery, wound healing, cell culture models, and tissue regeneration.

BackgroundTrastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated with the colon cancer 1 (MACC1) predicted poor prognosis of GC and promoted tumor cells proliferation and invasion. In this study, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 reversed this resistance.MethodsThe effect of trastuzumab and glycolysis inhibitor combination on cell viability, apoptosis, and cell metabolism was investigated in vitro using established trastuzumab-resistant GC cell lines. We assessed the impact of trastuzumab combined with oxamate on tumor growth and metabolism in an established xenograft model of HER2-positive GC cell lines.ResultsHere, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 in trastuzumab-resistant cells reversed this resistance. Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects. Moreover, when the PI3K/AKT signaling pathway was inhibited, the effects of MACC1 on resistance and glycolysis were diminished. Our findings indicated that MACC1 promoted the Warburg effect mainly through the PI3K/AKT signaling pathway, which further enhanced GC cells trastuzumab resistance.ConclusionsOur results indicate that co-targeting of HER2 and the Warburg effect reversed trastuzumab resistance in vitro and in vivo, suggesting that the combination might overcome trastuzumab resistance in MACC1-overexpressed, HER2-positive GC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0302-1) contains supplementary material, which is available to authorized users.

Our recent studies suggest a role for the proteasome activator REG (11S regulatory particles, 28-kDa proteasome activator)γ in the regulation of tumor protein 53 (p53). However, the molecular details and in vivo biological significance of REGγ-p53 interplay remain elusive. Here, we demonstrate that REGγ-deficient mice develop premature aging phenotypes that are associated with abnormal accumulation of casein kinase (CK) 1δ and p53. Antibody array analysis led us to identify CK1δ as a direct target of REGγ. Silencing CK1δ or inhibition of CK1δ activity prevented decay of murine double minute (Mdm)2. Interestingly, a massive increase of p53 in REGγ −/− tissues is associated with reduced Mdm2 protein levels despite that Mdm2 transcription is enhanced. Allelic p53 haplodeficiency in REGγ-deficient mice attenuated premature aging features. Furthermore, introducing exogenous Mdm2 to REGγ −/− MEFs significantly rescues the phenotype of cellular senescence, thereby establishing a REGγ-CK1-Mdm2-p53 regulatory pathway. Given the conflicting evidence regarding the "antiaging" and "proaging" effects of p53, our results indicate a key role for CK1δ-Mdm2-p53 regulation in the cellular aging process. These findings reveal a unique model that mimics acquired aging in mammals and indicates that modulating the activity of the REGγ-proteasome may be an approach for intervention in aging-associated disorders.casein kinase 1 | PA28γ P remature aging refers to unusual acceleration of the natural aging process and is induced by multiple factors such as genetics, environment, and stress conditions. Many biological markers of premature aging have been described over the past century, including blindness, gray/yellow hair, ear atrophy, osteoporosis, lordokyphosis of the spine, reduced hair regrowth, delayed wound healing, and a shortened lifespan (1, 2). Recently, progress has been made in understanding some of the mechanisms of premature aging (3, 4). DNA damage, oxidative stress, and mitochondrial DNA (mtDNA) mutations are associated with premature aging and may be contributing agents. Furthermore, abnormalities in several cancer-related proteins such as cyclin-dependent kinase inhibitor 1 (p21), tumor protein 53 (p53), and E2F family of transcription factors (retinoblastoma-associated protein; E2F1) also are known to cause premature aging phenotypes (5-8). Given that longer lifespan is mostly associated with an increased cancer incidence, maintaining the balance between longevity and reduced risk of cancer remains a formidable task.Discrepancies between proaging and antiaging effects of p53 were observed in different experimental systems. A p53 hypermorphic mouse model that harbored a mutant p53 allele (m-p53) displayed resistance to spontaneous cancers, a shortened lifespan, and premature aging phenotypes (2). The role of p53 in promoting aging is supported by a different mouse model, in which a 44-kDa truncated naturally occurring isoform of p53 (p44 +/+ ) is expressed (7). The p44 +/+ mice displayed enhanced p53 activity and phenot...

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Two-photon fluorescence lifetime imaging (TP-FLIM) not only permits imaging deep inside the tissues with precise spatial manipulation but also circumvents tissue autofluorescence, holding tremendous promise in molecular imaging. However, the serious lack of suitable contrast agents with long fluorescence lifetime and efficient two-photon absorption (TPA) greatly limits the advance of TP-FLIM. This study reports a simple approach to fabricate water-soluble organic semiconducting nanoparticles [thioxanthone (TXO) NPs] with ultralong fluorescence lifetime and efficient TPA for in vivo TP-FLIM. The approach utilizes the aggregation of a specifically selected thermally activated delayed fluorescence (TADF) fluorophore to prolong its fluorescence lifetime. Encapsulating the TADF fluorophore within an amphiphilic copolymer not only maximizes its aggregation but also obtains TXO NPs with efficient TPA. Importantly, as-prepared TXO NPs exhibit a considerably long fluorescence lifetime at a magnitude of 4.2 µs, which is almost 1000 times larger than that of existing organic contrast agents. Moreover, such long fluorescence lifetime is almost oxygen-inert, readily realizing both in vitro and in vivo TP-FLIM. This work may set valuable guidance for designing organic semiconducting materials with ultralong fluorescence lifetimes to fulfill the potential of FLIM.