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Structural morphology is the key parameter for efficacy of nanomedicine. To date, lipid-based nanomaterial has been the most widely used material in nanomedicine and many other biomedical applications. However, to the best of our knowledge, there has not been an in-depth or systematic investigation of the structure-function relationship of lipid-based nanostructures. In this report, we investigated the formulation of novel lipid-based nanostructures via simple tuning of lipid combinations. To prove this concept, we used a combination of various ratios of simple and common phospholipids with different chain lengths (14-carbon chain DMPC: 6-carbon chain DHPC) to find out whether a myriad of novel lipid nanostructures could be obtained. Interestingly, many combinations resulted in distinct lipid nanostructures. Drug encapsulation tests confirmed that they are able to load large amounts of drugs for biological application. In vivo anti-tumor efficacy revealed that certain lipid nanostructures possessed superior tumor retardation effects.

A simple and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, liquiritin, liquiritigenin, glycyrrhetinic acid, and glycyrrhizin in rat plasma after oral administration of Shaoyao-Gancao decoction, which is traditionally used in the treatment of polycystic ovary syndrome. The plasma samples were pretreated with methanol as precipitant. The method exhibited good linearity (correlation coefficient (R2 ) > 0.99) with lower quantification limits of 0.595-4.69 ng/mL for all analytes. Intra- and interbatch precision, accuracy, recovery, and stability of the method were all within accepted criteria. The results showed that the pharmacokinetic behaviors of the seven compounds were altered in the pathological status of polycystic ovary syndrome. Furthermore, a total of 36 metabolites were structurally identified based on their accurate masses and fragment ions. The major metabolic pathway involves phase I metabolic reactions (such as hydroxylation), phase II metabolic reactions (such as sulfation and glucuronidation conjugation) as well as the combined multiple-step metabolism. This study is the first report on the pharmacokinetic and metabolic information of Shaoyao-Gancao decoction in both normal and model rats, which would provide scientific evidences for the bioactive chemical basis of herbal medicines and also promote the clinical application of Shaoyao-Gancao decoction for treating polycystic ovary syndrome.

Vibrio parahaemolyticus causes not only various diseases in aquaculture animals but also seafood-borne illness in humans. Outer membrane proteins (OMPs) are species-specific proteins found in bilayer membranes of gram-negative bacteria. Egg yolk immunoglobulin (IgY) has been reported to serve as oral administration of antibodies against bacteria and virus. RESULTS The present research extracted and identified OMPs from V. parahaemolyticus, and then the extracted OMPs were used to immunize hens to obtain specific IgY. The efficacy of IgY against V. parahaemolyticus were investigated in vitro and in vivo. The specific IgY effectively inhibited the growth of V. parahaemolyticus in liquid medium rather than Escherichia coli and Staphylococcus aureus. Specific IgY antibodies were incorporated into extruded food pellets and fed to bacteria-challenged white pacific shrimp to observe the anti-bacterial effect in vivo. The bacterial loads in muscles of V. parahaemolyticus infected shrimp fed with specific IgY-included diets were significantly fewer than those fed with non-specific IgY-included diets. The superoxide dismutase activities in muscles of infected shrimp fed with specific IgY-included diets were significantly higher than the control group. CONCLUSION The results suggested that the specific IgY effectively inhibited the growth of V. parahaemolyticus and introduced passive immunity to shrimp. ? 2018 Society of Chemical Industry

Osteoclasts are bone-resorbing cells differentiated from macrophage/monocyte precursors in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). In vitro models are principally based on primary bone marrow macrophages (BMMs), but RAW 264.7 cells are frequently used because they are widely available, easy to culture, and more amenable to genetic manipulation than primary cells. Increasing evidence, however, has shown that the vastly different origins of these two cell types may have important effects on cell behavior. In particular, M-CSF is a prerequisite for the differentiation of BMMs, by promoting survival and proliferation and priming the cells for RANKL induction. RAW 264.7 cells readily form osteoclasts in the presence of RANKL, but M-CSF is not required. Based on these key differences, we sought to understand their functional implications and how it might affect osteoclast differentiation and related signaling pathways. Using a robust and high-throughput proteomics strategy, we quantified the global protein changes in osteoclasts derived from BMMs and RAW 264.7 cells at 1, 3, and 5 days of differentiation. Data are available via ProteomeXchange with the identifier PXD009610. Correlation analysis of the proteomes demonstrated low concordance between the two cell types (R2 ≈ 0.13). Bioinformatics analysis indicate that RANKL-dependent signaling was intact in RAW 264.7 cells, but biological processes known to be dependent on M-CSF were significantly different, including cell cycle control, cytoskeletal organization, and apoptosis. RAW 264.7 cells exhibited constitutive activation of Erk and Akt that was dependent on the activity of Abelson tyrosine kinase, and the timing of Erk and Akt activation was significantly different between BMMs and RAW 264.7 cells. Our findings provide the first evidence for major discrepancies between BMMs and RAW 264.7 cells, indicating that careful consideration is needed when using the RAW 264.7 cell line for studying M-CSF-dependent signaling and functions. © 2018 American Society for Bone and Mineral Research. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild-type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

Lanthanide (Ln) group elements have been attracting considerable attention owing to the distinct optical properties. The crystal-field surroundings of Ln ions in the host materials can determine their energy level splitting, which is of vital importance to tailor their optical properties. 2D MoS2 single crystals were utilized as the host material to embed Eu3+ and energy-level splitting was achieved for tuning its photoluminescence (PL). The high anisotropy of the 2D host materials makes them distort the degenerate orbitals of the Ln ions more efficiently than the symmetrical bulk host materials. A significant red-shift of the PL peak for Eu3+ was observed. The strategy for tailoring the energy level splitting of Ln ions by the highly designable 2D material crystal field provides a new method to extend their optical properties.

Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament‐associated protein 1 antisense RNA1 (lncAFAP1‐AS1) is identified as a key factor in inducing radioresistance of triple‐negative breast cancer (TNBC) via activating the Wnt/β‐catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction‐responsive nanoparticle (NP) platform is engineered for effective lncAFAP1‐AS1 siRNA (siAFAP1‐AS1) delivery. Systemic delivery of siAFAP1‐AS1 with the reduction‐responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1‐AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1‐AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1‐AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients.

Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus-sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side-effects. We report the development of a novel L-cysteine-based poly (disulfide amide) (Cys-PDSA) family for fabricating redox-triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt % docetaxel) and tunable properties. The polymers are synthesized through one-step rapid polycondensation of two nontoxic building blocks: L-cystine ester and versatile fatty diacids, which make the polymer redox responsive and give it a tunable polymer structure, respectively. Alterations to the diacid structure could rationally tune the physicochemical properties of the polymers and the corresponding NPs, leading to the control of NP size, hydrophobicity, degradation rate, redox response, and secondary self-assembly after NP reductive dissociation. In vitro and in vivo results demonstrate these NPs’ excellent biocompatibility, high selectivity of redox-triggered drug release, and significant anticancer performance. This system provides a promising strategy for advanced anticancer theranostic applications.

In this paper, we consider a downlink secondary cognitive radio multicast network that consists of a cognitive base station and a set of secondary multicast groups sharing spectrum with a primary network. To protect the transmissions of the primary network, an interference power constraint is applied to restrict the transmit power of the cognitive base station. The problem of joint channel and power allocation for the cognitive radio multicast network is studied. The objective is to minimise the weighted aggregate outage probability for a given target rate for the cognitive radio multicast network. Specifically, two types of outage probabilities, namely, group outage probability and individual outage probability, are considered. For each type of outage probability, the optimal joint channel and power allocation algorithm is proposed based on Lagrange dual optimisation. Simulation results are illustrated to verify the effectiveness of the proposed algorithms. It is shown that the proposed algorithms significantly improve the performance of the cognitive radio multicast network in terms of outage probability. Copyright © 2014 John Wiley & Sons, Ltd.

Biodegradable polymeric nanoparticles (NPs) have demonstrated significant potential to improve the systemic delivery of RNA interference (RNAi) therapeutics, such as small interfering RNA (siRNA), for cancer therapy. However, the slow and inefficient siRNA release inside tumor cells generally observed for most biodegradable polymeric NPs may result in compromised gene silencing efficacy. Herein, a biodegradable and redox-responsive NP platform, composed of a solid poly(disulfide amide) (PDSA)/cationic lipid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery to tumor cells, is developed. This newly generated NP platform can efficiently encapsulate siRNA under extracellular environments and can respond to the highly concentrated glutathione (GSH) in the cytoplasm to induce fast intracellular siRNA release. By screening a library of PDSA polymers with different structures and chain lengths, the optimized NP platform shows the unique features of i) long blood circulation, ii) high tumor accumulation, iii) fast GSH-triggered intracellular siRNA release, and iv) exceptionally effective gene silencing. Together with the facile polymer synthesis technique and robust NP formulation enabling scale-up, this new redox-responsive NP platform may become an effective tool for RNAi-based cancer therapy.

In this study, two types of BolA-like amphiphilic peptides with dual ligands comprising a tumor-targeting moiety of RGD sequence and a cell-penetrating moiety of R8 sequence are designed and synthesized as gene vectors. The BolA-structural peptide carriers can self-assemble into spherical nanoparticles with a hydrophilic core and shell, which are similar to the viral capsid and can bind plasmid DNA in an aqueous medium to form viral-mimetic complexes. It is found that the BolA-like dual ligands system exhibits significantly enhanced gene expression in both HeLa and 293T cell lines, as compared with poly(ethylenimine) PEI. These BolA-like amphiphilic peptides are promising in clinical trials of gene therapy.

A unique peptide nanofibrous indicator (NFI) is fabricated by mixing a borono-peptide with alizarin red S, followed by subsequent binding and self-assembly. The NFI thus obtained exhibits an intense response to sialyl Lewis X tetrasaccharide, which is overexpressed in human hepatocellular carcinoma cell lines. Importantly, this NFI has the capability of specifically recognizing human hepatocellular liver carcinoma (HepG2) cells through the eye-detectable color change resulting from strong binding-induced displacement. This novel technique for cancer cell identification through direct unaided eye judgment will open up an innovative platform for cancer cell detection.

SUMMARY This paper considers a downlink cognitive radio network consisting of one cognitive base station and multiple secondary users (SUs) that shares spectrum with a primary network. Unlike most of previous studies that focus on the SUs that carry only one type of service, in this paper, the SUs that carry heterogeneous services are considered. Specifically, the SUs are classified by service types, that is, the SUs that carry nonreal-time services and the SUs that carry real-time services. The QoS of the nonreal-time SUs is guaranteed by the minimum mean rate constraint, whereas the QoS of the real-time SUs is guaranteed by the minimum instantaneous rate constraint. Under this setup, a joint subchannel, rate, and power allocation scheme based on dual optimization method is proposed to minimize the mean transmit power consumption of the cognitive base station. The complexity of the proposed scheme is linear in the number of subchannels and the number of SUs. Extensive simulation results are provided to validate the proposed resource allocation scheme. Copyright © 2012 John Wiley & Sons, Ltd.