Efficient brain drug delivery has been a challenge in the treatment of Alzheimer's disease (AD) and other brain disorders as blood‐brain barrier (BBB) impedes most drugs to reach brain. To overcome ...this obstacle, a novel poly(lactic‐co‐glycolic acid) (PLGA) nanoparticle conjugated with CD47 extracellular domain via reactive oxygen species (ROS)‐responsive phenylborate ester bond exhibiting “do not eat me” signal and BBB penetrating peptide CRTIGPSVC (CRT) and microglia modulation agent Nec‐1s encapsulated in it is developed. The experimental results show that the designed nanoparticle efficiently increases its half‐life in blood circulation by preventing engulfment via phagocytes, and enhances its brain distribution by synergistic effect of CD47 and CRT. The high level of ROS in mouse brain releases CD47 from the nanoparticles and the resultant particles are effectively phagocytized by resident microglia. The engulfed Nec‐1s modulates pathological microglia to a beneficial state, which reduces Aβ burden, microgliosis and astrocytosis, decreases cytokine production and oxidative stress in the brains of AD mice, and finally attenuates cognition deficits and synapse loss. The results first demonstrate that the conditionally releasable “do not eat me” CD47 signal remarkably facilitates microglia‐targeted drug delivery and warrants further study to develop therapeutic agent for AD treatment.
A poly(lactic‐co‐glycolic acid) (PLGA) nanoparticle conjugated with the “do not eat me” CD47 signal via reactive oxygen species‐responsive bond and blood‐brain barrier penetrating peptide CRTIGPSVC is developed for microglia‐targeted Nec‐1s delivery. This nanoparticle shows increased brain distribution and microglial delivery of drug via conditionally releasable CD47 and can modulate pathological microglia to a beneficial state in Alzheimer's disease treatment.
Fast Image Interpolation via Random Forests Huang, Jun-Jie; Siu, Wan-Chi; Liu, Tian-Rui
IEEE transactions on image processing,
2015-Oct., 2015-Oct, 2015-10-00, 20151001, Letnik:
24, Številka:
10
Journal Article
Recenzirano
This paper proposes a two-stage framework for fast image interpolation via random forests (FIRF). The proposed FIRF method gives high accuracy, as well as requires low computation. The underlying ...idea of this proposed work is to apply random forests to classify the natural image patch space into numerous subspaces and learn a linear regression model for each subspace to map the low-resolution image patch to high-resolution image patch. The FIRF framework consists of two stages. Stage 1 of the framework removes most of the ringing and aliasing artifacts in the initial bicubic interpolated image, while Stage 2 further refines the Stage 1 interpolated image. By varying the number of decision trees in the random forests and the number of stages applied, the proposed FIRF method can realize computationally scalable image interpolation. Extensive experimental results show that the proposed FIRF(3, 2) method achieves more than 0.3 dB improvement in peak signal-to-noise ratio over the state-of-the-art nonlocal autoregressive modeling (NARM) method. Moreover, the proposed FIRF(1, 1) obtains similar or better results as NARM while only takes its 0.3% computational time.
Layered double hydroxide (LDH) is a 'sandwich'-like two-dimensional clay material that has been systematically investigated for biomedical application in the past two decades. LDH is an alum-similar ...adjuvant, which has a well-defined layered crystal structure and exhibits high adjuvanticity. The unique structure of LDH includes positively charged layers composed of divalent and trivalent cations and anion-exchangeable interlayer galleries. Among the many variants of LDH, MgAl-LDH (the cationic ions are Mg2+ and Al3+) has the highest affinity to antigens, bioadjuvants and drug molecules, and exhibits superior biosafety. Past research studies indicate that MgAl-LDH can simultaneously load antigens, bioadjuvants and molecular drugs to amplify the strength of immune responses, and induce broad-spectrum immune responses. Moreover, the size and dispersity of MgAl-LDH in biological environments can be well controlled to actively deliver antigens to the immune system, realizing the rapid induction and maintenance of durable immune responses. Furthermore, the functionalization of MgAl-LDH nanoadjuvants enables it to capture antigens in situ and induce personalized immune responses, thereby more effectively overcoming complex diseases. In this review, we comprehensively summarize the development and application of MgAl-LDH nanoparticles as a vaccine adjuvant, demonstrating that MgAl-LDH is the most potential adjuvant for clinical application.
It remains a great challenge to engineer materials with strong and stable interactions for the simultaneously mechanical-robust and room temperature phosphorescence-efficient materials. In this work, ...we demonstrate a covalent cross-linking strategy to engineer mechanical-robust room temperature phosphorescence materials through the B-O click reaction between chromophores, polyvinyl alcohol matrix and inorganic layered double hydroxide nanosheets. Through the covalent cross-linkage between the organic polyvinyl alcohol and inorganic layered double hydroxide, a polymeric composite with ultralong lifetime up to 1.45 s is acquired based on the inhibited non-radiative transition of chromophores. Simultaneously, decent mechanical strength of 97.9 MPa can be realized for the composite materials due to the dissipated loading stress through the covalent-bond-accommodated interfacial interaction. These cross-linked composites also exhibit flexibility, processability, scalability and phosphorescence responses towards the mechanical deformation. It is anticipated that the proposed covalent click reaction could provide a platform for the design and modulation of composites with multi-functionality and long-term durability.
Utilization of N,N‐dimethylformamide (DMF) as an amine source and reductant for synthesizing tertiary amines is a promising way to replace the substrates formaldehyde and dimethylamine, and it is ...desirable to seek porous acid‐resistant catalysts for heterogeneous catalysis of this reaction. Herein, a robust metal–organic framework (MOF) {Th6O4(OH)4(H2O)6(BCP)3⋅10 DMF}n (1) containing stacked nanocages with a diameter of 1.55 nm was constructed. Compound 1 can maintain its single‐crystal structure even kept in air at 400 °C for 3 h, and in DMF or water at 200 °C for 7 days. Density functional theory (DFT) calculations suggested that the high interaction energy between the Th6O4(OH)4(H2O)612+ clusters and ligands was responsible for the excellent stability of 1. Catalytic investigations revealed that 1 can effectively and size‐selectively catalyze the reductive amination of aldehydes with DMF, and it can be reused at least five times without obvious loss in catalytic activity.
A strong‐acid‐resistant Th6 cluster‐based framework containing stacked nanocages was constructed and demonstrated excellent efficiency and stability in the reductive amination of various aldehydes with N,N‐dimethylformamide as the amino source, reductant and solvent. In addition, this catalyst displayed a catalytic size‐selectivity for aldehydes that has not been observed previously for this reaction.
The orexin peptides (orexin A, orexin B) and their receptors (orexin receptor type 1, orexin receptor type 2) are involved in multiple physiological processes such as the regulation of ...sleep/wakefulness state, energy homeostasis and reward seeking. A result of this has been the development of small-molecule orexin receptor antagonists as novel therapies for the treatment of insomnia and drug addiction. Increased levels of signaling via the orexin peptide/receptor system may protect against obesity, while somewhat unexpectedly, orexins acting at orexin receptors induce dramatic apoptosis resulting in the significant reduction of cell growth in various cancer cell lines. Meanwhile, the orexin peptide/receptor system is also involved in cardiovascular modulation, neuroendocrine and reproduction regulation. This review summarizes the latest developments in deciphering the biology of orexin signaling as well as efforts to manipulate orexin signaling pharmacologically.
•The orexin signaling is involved in multiple physiological processes.•Orexins, unexpectedly, induce dramatic apoptosis in various cancer cell lines.•Orexin receptor agonists/antagonists can be used to treat multiple disorders.•The multi-functional property of orexin signaling is a double-edged sword.
Highlights • GPCR dysregulation can cause cancer, but the role of GPCRs in carcinogenesis has been largely ignored. • The latest developments suggest that GPCRs are among the most useful targets ...against diverse malignant cancers. • The selective ligands targeting GPCRs may provide novel and effective cancer therapeutics and indeed some anticancer compounds targeting GPCRs have entered clinical trials.
Hepatic ischemia‐reperfusion (IR) injury is the leading cause of liver dysfunction and failure after liver resection or transplantation and lacks effective therapeutic strategies. Here, we applied a ...systematic proteomic analysis to identify the prominent contributors to IR‐induced liver damage and promising therapeutic targets for this condition. Based on an unbiased proteomic analysis, we found that toll‐interacting protein (Tollip) expression was closely correlated with the hepatic IR process. RNA sequencing analysis and phenotypic examination showed a dramatically alleviated hepatic IR injury by Tollip deficiency both in vivo and in hepatocytes. Mechanistically, Tollip interacts with apoptosis signal‐regulating kinase 1 (ASK1) and facilitates the recruitment of tumor necrosis factor receptor–associated factor 6 (TRAF6) to ASK1, leading to enhanced ASK1 N‐terminal dimerization and the subsequent activation of downstream mitogen‐activated protein kinase (MAPK) signaling. Furthermore, the Tollip methionine and phenylalanine motif and TRAF6 ubiquitinating activity are required for Tollip‐regulated ASK1–MAPK axis activation. Conclusion: Tollip is a regulator of hepatic IR injury by facilitating ASK1 N‐terminal dimerization and the resultant c‐Jun N‐terminal kinase/p38 signaling activation. Inhibiting Tollip or its interaction with ASK1 might be promising therapeutic strategies for hepatic IR injury.
Redox‐active tetrathiafulvalene (TTF)‐based covalent organic frameworks (COFs) exhibit distinctive electrochemical and photoelectrical properties, but their prevalent two‐dimensional (2D) structure ...with densely packed TTF moieties limits the accessibility of redox center and constrains their potential applications. To overcome this challenge, an 8‐connected TTF linker (TTF‐8CHO) is designed as a new building block for the construction of three‐dimensional (3D) COFs. This approach led to the successful synthesis of a 3D COF with the bcu topology, designated as TTF‐8CHO‐COF. In comparison to its 2D counterpart employing a 4‐connected TTF linker, the 3D COF design enhances access to redox sites, facilitating controlled oxidation by I2 or Au3+ to tune physical properties. When irradiated with a 0.7 W cm−2 808 nm laser, the oxidized 3D COF samples (IX−${\mathrm{I}}_{\mathrm{X}}^{-}$@TTF‐8CHO‐COF and Au NPs@TTF‐8CHO‐COF) demonstrated rapid temperature increases of 239.3 and 146.1 °C, respectively, which surpassed those of pristine 3D COF (65.6 °C) and the 2D COF counterpart (6.4 °C increment after I2 treatment). Furthermore, the oxidation of the 3D COF heightened its photoelectrical responsiveness under 808 nm laser irradiation. This augmentation in photothermal and photoelectrical response can be attributed to the higher concentration of TTF·+ radicals generated through the oxidation of well‐exposed TTF moieties.
A new red‐ox active three‐dimensional (3D) covalent organic framework (COF) is synthesized by a tetrathiafulvalene (TTF)‐based 8‐connected building block. Because of the generations of stable TTF·+ states after oxidization, the systems show well‐tunable physical proprieties for near‐infrared photo‐thermal conversion and photo‐electrical response.
Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based ...vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and CpG onto LDH nanoparticles. Using melanoma as the model cancer and Tyrosinase-related protein 2 (Trp2) peptide as the model antigen, we demonstrated that dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth in comparison with aggregated LDH-based vaccine. We further constructed multi-target dispersion-stable LDH-based vaccine by co-loading Trp2, two mutated epitopes (M27 and M30) and CpG, which showed remarkable inhibition of melanoma growth. These results suggest that dispersion-stable LDH nanoparticles are an ideal platform to load multi-antigens and immune stimulants as effective personalized therapeutic cancer vaccines.
Display omitted
•Clear demonstration of constructing LDH-based multi-target therapeutic cancer vaccine.•The dispersion status is a key factor determining the anti-tumor immune responses.•Our multi-target vaccine promotes stronger antigen-specific CTL responses.•This vaccine very significantly inhibits the tumor growth (87% reduction in volume).
