Fast extraction of three-dimensional nanofiber orientation from WAXD patterns using machine learning.

Structural disclosure of biological materials can help our understanding of design disciplines in nature and inspire research for artificial materials. Synchrotron microfocus X-ray diffraction is one of the main techniques for characterizing hierarchically structured biological materials, especially the 3D orientation distribution of their interpenetrating nanofiber networks. However, extraction of 3D fiber orientation from X-ray patterns is still carried out by iterative parametric fitting, with disadvantages of time consumption and demand for expertise and initial parameter estimates. When faced with high-throughput experiments, existing analysis methods cannot meet the real time analysis challenges. In this work, using the assumption that the X-ray illuminated volume is dominated by two groups of nanofibers in a gradient biological composite, a machine-learning based method is proposed for fast and automatic fiber orientation metrics prediction from synchrotron X-ray micro-focused diffraction data. The simulated data were corrupted in the training procedure to guarantee the prediction ability of the trained machine-learning algorithm in real-world experimental data predictions. Label transformation was used to resolve the jump discontinuity problem when predicting angle parameters. The proposed method shows promise for application in the automatic data-processing pipeline for fast analysis of the vast data generated from multiscale diffraction-based tomography characterization of textured biomaterials.

Rational design of MoS2-supported Cu single-atom catalysts by machine learning potential for enhanced peroxidase-like activity.

Two-dimensional molybdenum disulfide (2D-MoS2)-supported single atom nanomaterials with enhanced enzyme-like activities are potential substitutes for natural enzymes due to their huge specific surface areas, ease of decoration, high catalytic activity and high catalytic stability. However, their catalytic mechanism remains unclear, making the rational design of nanozymes difficult to achieve. Herein, the mechanisms have been explored to enhance the peroxidase-like activity of MoS2 for H2O2 decomposition. Global neutral network (G-NN) potentials were constructed to accurately and quickly illustrate the mechanisms of MoS2 catalysts and their surface modifications. The high peroxidase-like activity of the MoS2-supported Cu single atom catalyst with sulfur vacancy (Cu@MoS2-Vs) in acidic conditions was systematically evaluated using the trained G-NN potential and density functional theory (DFT), as well as experimental validation. Further analysis of the geometric and electronic properties of pivotal stationary structures revealed the enhanced electron transfer process for high catalytic performance with the modulation of the Cu single atom loading, sulfur vacancy engineering and the surrounding acidic and alkaline environment regulation on the MoS2 basal plane. The results also showed that Cu@MoS2-Vs in an acidic environment exhibited the highest peroxidase-like activity. This work is expected to provide broad implications for the rational design of substrate-supported single-atom catalysts with superior performance and lower cost by surface modification and acidic and alkaline environment regulation.

Gold Nanorods Inhibit Tumor Metastasis by Regulating MMP-9 Activity: Implications for Radiotherapy.

Dysregulation of matrix metalloproteinase (MMP) is strongly implicated in tumor invasion and metastasis. Nanomaterials can interact with proteins and have impacts on protein activity, which provides a potential strategy for inhibiting tumor invasion and metastasis. However, the regulation of MMP activity by nanomaterials has not been fully determined. Herein, we have found that gold nanorods (Au NRs) are able to induce the change of the secondary structure of MMP-9 and thereby inhibit their activity. Interestingly, the inhibition of MMP-9 activity is highly dependent on the aspect ratio of Au NRs, and an aspect ratio of 3.3 shows the maximum inhibition efficiency. Molecular dynamics simulations combined with mathematical statistics algorithm reveal the binding behaviors and interaction modes of MMP-9 with Au NRs in atomic details and disclose the mechanism of aspect ratio-dependent inhibition effect of Au NRs on MMP-9 activity. Au NRs with an aspect ratio of 3.3 successfully suppress the X-ray-activated invasion and metastasis of tumor by inhibiting MMP-9 activity. Our findings provide important guidance for the modulation of MMP-9 activity by tuning key parameters of nanomaterials and demonstrate that gold nanorods could be developed as potential MMP inhibitors.

The incorporation of peach gum polysaccharide into soy protein based microparticles improves probiotic bacterial survival during simulated gastrointestinal digestion and storage.

The objective of this research was to investigate the in vitro gastrointestinal digestion and storage properties of Lactobacillus plantarum 550 encapsulated in soy protein isolate (SPI) and peach gum polysaccharide (PG) through spray drying. High survival rates (>8.1 Log CFU/g) were obtained for all encapsulation formulas containing PG. Combination of SPI and PG showed positive effects on both gastric resistance and storage stability of cells. Among the formulas tested, sample of SPI:PG = 3:1 showed the highest survival (7.88 ± 0.12 Log CFU/g), corresponding to the strongest electrostatic interaction between SPI and PG. With PG content increasing, the storage stability of probiotic was also enhanced, as PG could reduce the moisture content within microcapsules as well as scavenge free radicals generated during storage. In conclusion, the current study demonstrates that SPI combined with PG may provide effective protection to cells not only during spray drying, but also during storage and gastrointestinal digestion.

Catalase-Like Nanozymes: Classification, Catalytic Mechanisms, and Their Applications.

The field of nanozymes has developed rapidly over the past decade. Among various oxidoreductases mimics, catalase (CAT)-like nanozyme, acting as an essential part of the regulation of reactive oxygen species (ROS), has attracted extensive research interest in recent years. However, CAT-like nanozymes are not as well discussed as other nanozymes such as peroxidase (POD)-like nanozymes, etc. Compared with natural catalase or artificial CAT enzymes, CAT-like nanozymes have unique properties of low cost, size-dependent properties, high catalytic activity and stability, and easy surface modification, etc., which make them widely used in various fields, especially in tumor therapy and disease treatment. Consequently, there is a great requirement to make a systematic discussion on CAT-like nanozymes. In this review, some key aspects of CAT-like nanozymes are deeply summarized as: 1) Typical CAT-like nanozymes classified by different nanomaterials; 2) The catalytic mechanisms proposed by experimental and theoretical studies; 3) Extensive applications in regard to tumor therapy, cytoprotection and sensing. Therefore, it is prospected that this review will contribute to the further design of CAT-like nanozymes and optimize their applications with much higher efficiency than before.

A bioactivated in vivo assembly nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative imaging.

Real-time imaging of the tumour boundary is important during surgery to ensure that sufficient tumour tissue has been removed. However, the current fluorescence probes for bioimaging suffer from poor tumour specificity and narrow application of the imaging window used. Here, we report a bioactivated in vivo assembly (BIVA) nanotechnology, demonstrating a general optical probe with enhanced tumour accumulation and prolonged imaging window. The BIVA probe exhibits active targeting and assembly induced retention effect, which improves selectivity to tumours. The surface specific nanofiber assembly on the tumour surface increases the accumulation of probe at the boundary of the tumor. The blood circulation time of the BIVA probe is prolonged by 110 min compared to idocyanine green. The assembly induced metabolic stability broaden the difference between the tumor and background, obtaining a delayed imaging window between 8-96 h with better signal-to-background contrast (>9 folds). The fabricated BIVA probe permits precise imaging of small sized (<2 mm) orthotopic pancreatic tumors in vivo. The high specificity and sensitivity of the BIVA probe may further benefit the intraoperative imaging in a clinical setting.

The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS2 nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS2 leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.

Rationally designed modular drug delivery platform based on intracellular peptide self-assembly.

Modulated molecular design-based intracellular self-assembly strategy has showed great potentiality in drug delivery, due to its assembling nature-resulted optimized drug biodistribution and metabolism. The modular designing concept endows the delivery system multiple functions, such as, selectivity and universality to improve the pharmacokinetics of loaded drugs. However, the accurate controlling of the self-assembling process in desired site to achieve optimal drug delivery is posed great challenges toward rational molecular design. Here, we fabricated a modulated drug-delivery system (MDS) through intracellular peptide self-assembly to realize effective drug delivery. MDS was designed based on modulated molecular designing strategy which contains five functional motifs and effectively transformed into fibrous nanostructures inside target cells by caspase3/7 hydrolysis directed in situ self-assembly. The experimental studies and molecular simulations were carried out to evaluate the successful construction and delivering efficacy of MDS. According to the experimental results and molecular simulation analysis, the percentage of solvent-exposed surface area of assembling modular (KLVFFAE), as well as its non-covalent interaction between four other modules synergeticly decide the solubility of molecules. The weak intramolecular forces of the peptide back bone, such as, hydrogen bond, as well as multivalent interactions of the side chains such as, salt bridge and hydrophobic interaction both contribute to the self-assembly of the molecules. The significant structural difference between delivering molecules optimize the system to adapt hydrophilic and hydrophobic drugs. Finally, the predicted drug delivery molecule specifically recognizes targeted cancer cell lines and self-assembles to form fibers intracellularly, resulting in prolonged drug retention and accumulation. The regular prediction and rational molecular design will benefit the further construction and optimization of modulated drug delivery platform.