IC9600: A Benchmark Dataset for Automatic Image Complexity Assessment.

Image complexity (IC) is an essential visual perception for human beings to understand an image. However, explicitly evaluating the IC is challenging, and has long been overlooked since, on the one hand, the evaluation of IC is relatively subjective due to its dependence on human perception, and on the other hand, the IC is semantic-dependent while real-world images are diverse. To facilitate the research of IC assessment in this deep learning era, we built the first, to our best knowledge, large-scale IC dataset with 9,600 well-annotated images. The images are of diverse areas such as abstract, paintings and real-world scenes, each of which is elaborately annotated by 17 human contributors. Powered by this high-quality dataset, we further provide a base model to predict the IC scores and estimate the complexity density maps in a weakly supervised way. The model is verified to be effective, and correlates well with human perception (with the Pearson correlation coefficient being 0.949). Last but not the least, we have empirically validated that the exploration of IC can provide auxiliary information and boost the performance of a wide range of computer vision tasks. The dataset and source code can be found at https://github.com/tinglyfeng/IC9600.

Long non-coding RNA MIR31HG as a prognostic predictor for malignant cancers: A meta- and bioinformatics analysis.

BACKGROUND: The possible regulatory mechanism of MIR31HG in human cancers remains unclear, and reported results of the prognostic significance of MIR31HG expression are inconsistent. METHODS: The meta-analysis and related bioinformatics analysis were conducted to evaluate the role of MIR31HG in tumor progression. RESULTS: The result showed that high MIR31HG expression was not related to prognosis. However, in the stratified analysis, we found that the overexpression of MIR31HG resulted in worse OS, advanced TNM stage, and tumor differentiation in respiratory system cancers. Moreover, our results also found that MIR31HG overexpression was related to shorter OS in cervical cancer patients and head and neck tumors. In contrast, the MIR31HG was lower in digestive system tumors which contributed to shorter overall survival, advanced TNM stage, and distant metastasis. Furthermore, the bioinformatics analysis showed that MIR31HG was highly expressed in normal urinary bladder, small intestine, esophagus, stomach, and duodenum and low in colon, lung, and ovary. The results obtained from FireBrowse indicated that MIR31HG was highly expressed in LUSC, CESC, HNSC, and LUAD and low in STAD and BLCA. Gene Ontology analysis showed that the co-expressed genes of MIR31HG were most enriched in the biological processes of peptide metabolism and KEGG pathways were most enriched in Ras, Rap1, and PI3K-Akt signaling pathway. CONCLUSION: MIR31HG may serve as a potential biomarker in human cancers.

Bifurcated Backbone Strategy for RGB-D Salient Object Detection.

Multi-level feature fusion is a fundamental topic in computer vision. It has been exploited to detect, segment and classify objects at various scales. When multi-level features meet multi-modal cues, the optimal feature aggregation and multi-modal learning strategy become a hot potato. In this paper, we leverage the inherent multi-modal and multi-level nature of RGB-D salient object detection to devise a novel Bifurcated Backbone Strategy Network (BBS-Net). Our architecture, is simple, efficient, and backbone-independent. In particular, first, we propose to regroup the multi-level features into teacher and student features using a bifurcated backbone strategy (BBS). Second, we introduce a depth-enhanced module (DEM) to excavate informative depth cues from the channel and spatial views. Then, RGB and depth modalities are fused in a complementary way. Extensive experiments show that BBS-Net significantly outperforms 18 state-of-the-art (SOTA) models on eight challenging datasets under five evaluation measures, demonstrating the superiority of our approach (~4% improvement in S-measure vs . the top-ranked model: DMRA). In addition, we provide a comprehensive analysis on the generalization ability of different RGB-D datasets and provide a powerful training set for future research. The complete algorithm, benchmark results, and post-processing toolbox are publicly available at https://github.com/zyjwuyan/BBS-Net.

Oral bioavailability of curcumin: problems and advancements.

Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions.

New progress and prospects: The application of nanogel in drug delivery.

Nanogel has attracted considerable attention as one of the most versatile drug delivery systems especially for site-specific and/or time-controlled delivery of bioactive agents owing to their combining features of hydrogel and nanoparticle. Physically synthesized nanogels can offer a platform to encapsulate various types of bioactive compounds, particularly hydrophobic drugs and biomacromolecules, but they have poor mechanical stability, whereas nanogels prepared by chemical cross-link have a wider application and larger flexibility. As an ideal drug-delivery carrier, nanogel has excellent drug loading capacity, high stability, biologic consistence and response to a wide variety of environmental stimuli. Nowadays, targeting and response especially multi-response of the nanogel system for drug delivery have become an issue in research. And the application study of nanogels mainly focuses on antitumor agents and proteins. This review focuses on the formation of nanogels (physical and chemical cross-linking) and their release behavior. Recent application of nanogels is also discussed.

RETRACTED ARTICLE: Preparation and characterization of novel lipid nanocapsules of ropivacaine for transdermal delivery.

Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, the application form used in clinic, ropivacaine hydrochloride (Naropin Injection), which should be administed intravenously, is causing poor patient convenience. The purpose of this study was to formulate ropivacaine (RPV) in lipid nanocapsules (LNCs) and character the potential of LNCs in delivering RPV transdermally to exploit novel external preparation. The RPV-LNCs were successfully prepared by phase inversion technique and the formulation was characterized in terms of size, zeta potential, ex vivo permeation study, and pharmacodynamics. The prepared RPV-LNCs displayed a typical core-shell structure with a narrow size distribution of 62.1 ± 1.7 nm and drug loading of 1.35 ± 0.20%. The results of differential scanning calorimetry (DSC) analysis and X-ray diffraction showed that RPV was in amorphous crystalline state when encapsulated into LNCs. Furthermore, the results of ex vivo permeation study displayed that RPV-LNCs had an improved permeability (349.0 ± 11.5 µg cm(-2) versus 161.0 ± 1.3 µg cm(-2)) compared with free RPV. The results of histopathology study showed that interaction between LNCs and skin could break the close conjugation of corneocyte layers. In the mice writhing test, RPV-LNCs exhibited obvious analgesic effect by both prolonging pain latency and reducing the writhing response with an inhibition rate of 91.3% compared to the control group. In conclusion, RPV-LNCs could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.

Preparation and Characterization of Puerarin-Loaded Lipid Nanocapsules.

The puerarin-loaded lipid nanocapsules (PUE-LNCs), composed of labrafac, lipoid and water, were prepared with a phase inversion procedure. The formulation was optimized by simplex lattice design and characterized for its size, zeta potential and in vitro drug release. The results showed that the PUE-LNCs performed a homogeneous typical core-shell structure under transmission electron microscope (TEM). The entrapment efficiency and drug loading were 56.61 ± 0.27% and 2.62 ± 0.12%, respectively. In vitro drug release revealed the PUE-LNCs showed a controlled-release manner in both artificial simulated gastric juice (pH 1.0) and artificial simulated intestinal fluid (pH 6.8). Based on the aforementioned results, it should now allow a promising tuning for further applications of LNCs as a drug delivery system for puerarin.

Breaking the skin barrier: achievements and future directions.

Skin delivery is more advantageous for drug administration than other routes since it is more compliant and can avoid the first-pass metabolic effect. More importantly, it can ensure stable blood level of transdermal drugs for a long period of time, avoiding fluctuation and reducing side effects. However, it is restricted by the barrier function of the stratum corneum. Therefore, significant attention has been paid to developing methods to modify the kinetics of skin drug delivery and expand the range of drugs that can be used for transdermal delivery. Novel mechanisms of increasing the intercellular and appendages penetration pathways have also been developed. This review focuses on chemical penetration enhancers, physical permeabilization (sonophoresis, iontophoresis and microneedles) and novel nanocarriers for skin delivery. Recent developments on skin delivery are also discussed.

Ethosomes for skin delivery of ropivacaine: preparation, characterization and ex vivo penetration properties.

Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, Naropin® Injection, the applied form in clinic, can cause patient non-convenience. The purpose of this study was to formulate ropivacaine (RPV) in ethosomes and evaluate the potential of ethosome formulation in delivering RPV transdermally. The RPV-loaded ethosomes were prepared with thin-film dispersion technique and the formulation was characterized in terms of size, zeta potential, differential scanning calorimetry (DSC) analysis and X-ray diffraction (XRD) study. The results showed that the optimized RPV-ethosomes displayed a typical lipid bilayer structure with a narrow size distribution of 73.86 ± 2.40 nm and drug loading of 8.27 ± 0.37%, EE of 68.92 ± 0.29%. The results of DSC and XRD study indicated that RPV was in amorphous state when encapsulated into ethosomes. Furthermore, the results of ex vivo permeation study proved that RPV-ethosomes could promote the permeability in a high-efficient, rapid way (349.0 ± 11.5 µg cm(-2) at 12 h and 178.8 ± 7.1 µg cm(-2) at 0.5 h). The outcomes of histopathology study forecasted that the interaction between ethosomes and skin could loosen the tight conjugation of corneocyte layers and weaken the permeation barrier. In conclusion, RPV-ethosomes could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.

Ropivacaine loaded microemulsion and microemulsion-based gel for transdermal delivery: preparation, optimization, and evaluation.

The objective of the present study was to prepare and evaluate a ropivacaine-loaded microemulsion (ME) formulation and microemulsion-based Carbopol gel (ME-gel) for transdermal delivery. Pseudo-ternary phase diagrams and a simplex lattice experiment design were utilized to screen and optimize the ME formulation. In the process, drug solubility and particle size were inspected as dependent variables whilst Capryol(®) 90 (X1), Smix (X2, Labrasol(®): absolute ethanol=1:2 w/w), water (X3) as independent variables. Following the optimization, the optimal ME formulation was comprised of 15% Capryol(®) 90, 53% Smix, and 32% water, respectively. Ropivacaine loaded ME appeared to be spherical under transmission electron microscope, and the average particle size was 58.79 nm. The results of ex vivo permeation study showed that ropivacaine had a significant higher cumulative amount from ME than that from ME-gel. Histopathology study elucidated that the microstructure of skin surface was significantly changed by the treatment of ME formulation. Skin irritation study indicated that neither ME nor ME-gel caused any irritation responses. Both ME and ME-gel presented a remarkable analgesic activity on acetic acid-induced writhing in mice. In conclusion, ME could be a promising formulation for ropivacaine transdermally administration.

Advances in lipid-based colloid systems as drug carrier for topic delivery.

INTRODUCTION: Based on the advantages of transcutaneous delivery and the application status of nanocarriers in transcutaneous delivery, this paper critically reviews the correlation of using different lipid-based colloid systems as permeation enhancement model. Particularly noteworthy, mechanisms of different action pathways of lipid-based colloid systems for topic delivery are illustrated, including free drug pathway, lipids enhancement, penetration with intact carrier and transappendageal pathway. AREAS COVERED: The authors focus on theories and detailed researches about liposome, lipid nanocapsules, solid lipid nanoparticles and microemulsion and nanostructured lipid carriers, revealing the advances and application states of these carriers as transcutaneous delivery system. FORWARD LOOK: Although lipid-based colloid systems show great superiority, some forward-looking ideas should be brought on agendas. In the future, more attention should be focused on skin stimulation. Mechanisms must be established to secure more information about the influence of excipient matrix. Some other issues including smart preparation forms and storage stability are also of current concerns and need more detailed research.

Lipid nanocapsules for transdermal delivery of ropivacaine: in vitro and in vivo evaluation.

The objective of this research was to develop novel ropivacaine-loaded lipid nanocapsules (RPV-LNCs) and evaluate the potential of RPV-LNCs as external preparation for transdermal delivery. RPV-LNCs were prepared by phase inversion technique and optimized by response surface design. The permeation ability of RPV-LNCs was characterized both in vitro and in vivo. The results showed that the optimized RPV-LNCs represented typical core-shell structure with the mean diameter of 62.1±1.7 nm. The entrapment efficiency and drug loading were 92.6±1.3% and 1.35±0.20%, respectively. Moreover, the cumulative amount of RPV penetrated through excised skin from LNCs was 2.17 folds than that of the propylene glycol. In vivo, RPV-LNCs contributed a higher RPV concentration in plasma (5.743 µg/mL). The RPV retained within dermis was 27.9±5.2 µg/mL for LNCs, obviously remarkable than that of the propylene glycol group (15.6±3.9 µg/mL). The skin histopathology study and scanning electron microscope (SEM) showed that interaction between LNCs and skin surface changed the apparent morphology of stratumcorneum and broke the close conjugation of corneocyte layers. All the detailed evidence showed that LNCs could provide a promising tuning as a transdermal delivery system of ropivacaine.

Advances in the formulations of non-injection administration of docetaxel.

Docetaxel is one of the most important anti-tumor drugs and has shown powerful therapeutic activity against breast cancer, non-small cell lung cancer, prostate cancer and so on. Owing to its poor water solubility and the efflux by P-glycoprotein (P-gp) and metabolism by CYP3A4 enzymes, it is generally administered as an injection form, the only manner for the current clinical application. However, the injection bearing polysorbate 80 and ethanol may cause adverse events such as severe hypersensitivity reactions, neutropenia, neurotoxicity, musculoskeletal toxicity and cumulative fluid retention, these adverse events limit clinical application and commercialization of docetaxel. Recently, various kinds of non-injection delivery systems for docetaxel have been developed to eliminate the polysorbate 80-based vehicle and increase the drug solubility. In this review, the non-injection delivery formulations of docetaxel for oral route, transdermal delivery, lung and rectal administration were discussed for future study and clinical application.

Preparation and evaluation of folate-modified lipid nanocapsules for quercetin delivery.

Folate-modified lipid nanocapsule encapsulated quercetin (QT-FALNC) was prepared with phase inversion method. The formulation was optimized by simplex lattice design with encapsulation efficiency and drug loading as index. The encapsulation efficiency and drug loading of the optimal formulation were 96.01% and 2.98%, respectively. The drug concentration in QT-FALNC suspension was 4.29 mg/mL. Under transmission electron microscopy, the QT-FALNC showed spherical shape with a narrow size distribution. The particle size and zeta potential of QT-FALNC were 36.2 nm and -4.76 mV, respectively. The pharmacokinetics study in rats showed that the mean retention time (MRT0-∞) of the non-targeting lipid nanocapsules (LNC) loading quercetin (QT-LNC) and the targeting QT-FALNC was 12.981 h and 15.086 h, respectively, indicating that LNC could prolong the effect of QT in vivo. The in vitro anti-proliferative activity and cellar uptake of QT-FALNC were studied on Hela and MCF-7/MDR cells. The results showed that both QT-LNC and QT-FALNC displayed a stronger cell-killing effect than free QT. The in vivo anti-tumor study indicated that both QT-LNC and QT-FALNC showed the significant inhibition effect on tumor growth in H22 tumor-bearing mice compared with the control. It can be concluded that lipid nanocapsule is a potential carrier for improving solubility and biological activity of QT.

Preparation and in vitro evaluation of apigenin loaded lipid nanocapsules.

In the present study, apigenin loaded lipid nanocapsules (AP-LNC) was prepared with phase inversion method and the formulation was optimized by simplex lattice design experiment with drug loading and encapsulation efficiency as the indexes. The drug loading and encapsulation efficiency of the optimal AP-LNC formulation were 1.26 +/- 0.05% and 95.86 +/- 0.38%, respectively. The drug concentration in the AP-LNC solution was 5.88 mg/mL. The shape of the AP-LNC was spherical with good dispersion. The average particle size and zeta potential of the AP-LNC were 46.1 nm and - 28.18 mV, respectively. The in vitro release experiments showed that the release behavior of AP from LNC fitted the two phase dynamics process. The anti-proliferative activity of the AP-LNC was investigated using the MTT assay, and the results showed AP-LNC could significantly enhance the inhibition rate to HepG2 cell and MCF-7 cell. It could be concluded that LNC was a potential carrier for improving solubility and biological activity of AP.

Polymer-drug conjugates: present state of play and future perspectives.

Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic polymer-drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs. Additionally, the most recent achievements in the polymer-drug conjugate field and several promising approaches for the future are discussed.

[Preparation and in vitro characterization of apigemin-loaded nanostructured lipid carriers].

OBJECTIVE: To prepare Apigemin-loaded nanostructured lipid carriers (Api-NLCs) and evaluate their characteristics. METHODS: Api-NLCs were prepared by the method of emulsion evaporation-solidification at low temperature. The physicochemical properties such as morphology, size distribution, zeta potential, entrapment efficiency, drug loading and drug release in vitro were evaluated. RESULTS: The obtained nanoparticles were spherical under transmission electron microscope. The mean diameter was 212.1 nm, the zeta potential was - 14.65 mV, the mean entrapment efficiency was 82.4% and the mean drug loading was 0.97%. The total drug release was 30% in 2 hours followed by a slow and sustained release in vitro. CONCLUSION: The optimal Api-NLCs show stable characteristics and broad prospects for application.

[Preparation and characterization of curcumin polybutylcyanoacrylate nanoparticles].

OBJECTIVE: To prepare curcumin polybutylcyanoacrylate nanoparticles (Cur-PBCNs) and evaluate its characteristics. METHODS: Cur-PBCNs were prepared by emulsion polymerization, and the formulation was optimized by L16 (4(3)) orthogonal design test with entrapment efficiency and drug loading as indices. In addition, its characteristics were investigated. RESULTS: The nanoparticles were spherical in appearance under transmission electron microscope (TEM). The mean diameter of the nanoparticles was 93.8 nm, the mean entrapment efficiency was (50.4 +/- 2.2)%, the mean drug-loading was (33.5 +/- 0.9)% and the Zeta potential was -6.81 mV. The total drug release was 34.74% in 2 hours followed by a sustained release in vitro for Cur-PBCNs, and the in vitro release profile of the nanoparticles was fit for two phases kinetics equation: 100 - Q = 4.5235e(-0.1724t) + 4.1641e(-0.0114t). CONCLUSION: The optimal Cur-PBCNs show good characteristics and sustained release character in vitro.