Metal-phenolic networks (MPNs) have shown promising potential in biomedical applications since they provide a rapid, simple and robust way to construct multifunctional nanoplatforms. As a novel ...nanomaterial self-assembled from metal ions and polyphenols, MPNs can be prepared to assist the theranostics of cancer owing to their bio-adhesiveness, good biocompatibility, versatile drug loading, and stimuli-responsive profile. This Critical Review aims to summarize recent progress in MPN-based nanoplatforms for multimodal tumor therapy and imaging. First, the advantages of MPNs as drug carriers are summarized. Then, various tumor therapeutic modalities based on MPNs are introduced. Next, MPN-based theranostic systems are reviewed. In terms of
in vivo
applications, specific attention is paid to their biosafety, biodistribution, as well as excretion. Finally, some problems and limitations of MPNs are discussed, along with a future perspective on the field.
Schematic showing the properties and theranostics applications of MPNs-based nanoplatforms.
In this paper, eight new galaxamide analogues (
~
) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT ...assays. The modified analogue
displayed broad spectrum cytotoxic activity toward each tested cell line with IC
values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) μg/mL, respectively. The galaxamides
and
induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells.
Nanoscale metal–organic frameworks (nMOFs) have gained increasingly more attention as attractive support materials in the immobilization and delivery of proteins for disease theranostics in recent ...years owing to their various advantages, such as large specific surface areas, well-ordered pore structures, aperture channel distributions, and ease of functionalization. Here, we present an overview of recent progress in nMOF–protein composites for disease theranostics. First, advantages and construction strategies of nMOF–protein composites as drug carriers are introduced. Then, therapeutic modalities and theranostic nanosystems based on nMOF–protein composites are reviewed. Next, we pay specific attention to their biosafety, biodistribution, and excretion in vivo. Finally, the challenges and limitations of nMOF–protein composites for biomedical applications are discussed, along with future perspectives in the field.
Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To ...address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.
•The memory issue in FGM is solved by combining with ANN.•An error control method is proposed to increase FGM-ANN accuracy.•LES of spray combustion is conducted using FGM-ANN.•CEMA is used to ...identify local combustion modes.
Display omitted
In the present work, artificial neural networks (ANN) technique combined with flamelet generated manifolds (FGM) is proposed to mitigate the memory issue of FGM models. A set of ANN models is firstly trained using a 68-species mass fractions in mixture fraction-progress variable space. The ANN prediction accuracy is examined in large eddy simulation (LES) and Reynolds averaged Navier-Stokes (RANS) simulations of spray combustion. It is shown that the present ANN models can properly replicate the FGM table for most of the species mass fractions. The network models with relative error less than 5% are considered in RANS and LES to simulate the Engine Combustion Network (ECN) Spray H flames. Validation of the method is firstly conducted in the framework of RANS. Both non-reacting and reacting cases show the present method predicts very well the trend of spray and combustion process under different ambient temperatures. The results show that FGM-ANN can replicate the ignition delay time (IDT) and lift-off length (LOL) precisely as the conventional FGM method, and the results agree very well with the experiments. With the help of ANN, it is possible to achieve high efficiency and accuracy, with a significantly reduced memory requirement of the FGM models. LES with FGM-ANN is then applied to explore the detailed spray combustion process. Chemical explosive mode analysis (CEMA) approach is used to identify the local combustion modes. It is found that before the spray flame is developed to the steady-state, the high CH2O zone is always associated with ignition mode. However, high CH2O zone together with high OH zone is dominated by the burned mode after the steady-state. The lift-off position is dominated mainly by the diffusion mode.
A plasma-assisted internal combustion engine model is established based on detailed plasma kinetics, combustion kinetics, and physical compression/expansion processes. The effects of nanosecond ...repetitively pulsed discharge (NRPD) on plasma-assisted ignition characteristics of mixtures under different fuel concentrations are studied under HCCI engine-relevant conditions. The coupled plasma and chemical kinetic model are validated with experiments. The comparison between NRPD and thermal ignition with a certain amount of input energy is carried out, and the results show that the former can ignite a mixture owing to the kinetic effect of nonequilibrium plasma, but the latter cannot ensure ignition. Path flux analysis shows that excited states and electrons react with fuel, providing O and H directly, increasing the possibility of ignition at a low temperature. The effect of NRPD on combustion performance under various equivalence ratios (
φ
) is investigated. It was found that in ICEs with NRPD, the ignition delay time under the lean-burn condition (
φ
= 0.5) is the shortest among three demonstrative cases. Even though the leaner mixture case with
φ
= 0.2 is more favorable for the production of O and OH during the discharge, after discharge, the heat release in case 2 with
φ
= 0.5 dramatically increases, resulting in the temperature exceeding that in the ultra-lean case. As the piston moves up, the higher amounts of CH
3
, HO
2
, and H
2
O
2
as well as higher temperature for the lean-burn (
φ
= 0.5) case lead to the rapid increase of OH and O, which accelerates the consumption of methane and finally the earliest hot ignition near TDC. Finally, a series of parameter studies are performed to show the effects of
E/N
, current density,
φ
, and discharge timing on the ignition process. The results suggest that discharge parameters
E/N
and current density together with discharge timings and equivalence ratios can improve ignitability in internal combustion engines.
•Achieve 1D + 3D coupled simulation of PV2S aircraft engine gas exchange.•A DoE and GA approach for high-altitude performance of PV2S aircraft piston engine.•High-altitude valve timing optimization ...by DoE and GA is realized.•Analyze the influence of valve overlap and duration angle at various altitudes.•Study high-altitude gas exchange performance with different conditions.
The poppet valves two-stroke (PV2S) aircraft engine fueled with sustainable aviation fuel is a promising option for general aviation and unmanned aerial vehicle propulsion due to its high power-to-weight ratio, uniform torque output, and flexible valve timings. However, its high-altitude gas exchange performance remains unexplored, presenting new opportunities for optimization through artificial intelligence (AI) technology. This study uses validated 1D + 3D models to evaluate the high-altitude gas exchange performance of PV2S aircraft engines. The valve timings of the PV2S engine exhibit considerable flexibility, thus the Latin hypercube design of experiments (DoE) methodology is employed to fit a response surface model. A genetic algorithm (GA) is applied to iteratively optimize valve timings for varying altitudes. The optimization process reveals that increasing the intake duration while decreasing the exhaust duration and valve overlap angles can significantly enhance high-altitude gas exchange performance. The optimal valve overlap angle emerged as 93 °CA at sea level and 82 °CA at 4000 m altitude. The effects of operating parameters, including engine speed, load, and exhaust back pressure, on the gas exchange process at varying altitudes are further investigated. The higher engine speed increases trapping efficiency but decreases the delivery ratio and charging efficiency at various altitudes. This effect is especially pronounced at elevated altitudes. The increase in exhaust back pressure will significantly reduce the delivery ratio and increase the trapping efficiency. This study demonstrates that integrating DoE with AI algorithms can enhance the high-altitude performance of aircraft engines, serving as a valuable reference for further optimization efforts.
Display omitted
Galaxamide, an extract from
, is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its ...analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG₂), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG₂ cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG₂ cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG₂ cells.
Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such ...as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa) comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1-2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin), respectively.
PDF
