Swin-cryoEM: Multi-class cryo-electron micrographs single particle mixed detection method.

Cryo-electron micrograph images have various characteristics such as varying sizes, shapes, and distribution densities of individual particles, severe background noise, high levels of impurities, irregular shapes, blurred edges, and similar color to the background. How to demonstrate good adaptability in the field of image vision by picking up single particles from multiple types of cryo-electron micrographs is currently a challenge in the field of cryo-electron micrographs. This paper combines the characteristics of the MixUp hybrid enhancement algorithm, enhances the image feature information in the pre-processing stage, builds a feature perception network based on the channel self-attention mechanism in the forward network of the Swin Transformer model network, achieving adaptive adjustment of self-attention mechanism between different single particles, increasing the network's tolerance to noise, Incorporating PReLU activation function to enhance information exchange between pixel blocks of different single particles, and combining the Cross-Entropy function with the softmax function to construct a classification network based on Swin Transformer suitable for cryo-electron micrograph single particle detection model (Swin-cryoEM), achieving mixed detection of multiple types of single particles. Swin-cryoEM algorithm can better solve the problem of good adaptability in picking single particles of many types of cryo-electron micrographs, improve the accuracy and generalization ability of the single particle picking method, and provide high-quality data support for the three-dimensional reconstruction of a single particle. In this paper, ablation experiments and comparison experiments were designed to evaluate and compare Swin-cryoEM algorithms in detail and comprehensively on multiple datasets. The Average Precision is an important evaluation index of the evaluation model, and the optimal Average Precision reached 95.5% in the training stage Swin-cryoEM, and the single particle picking performance was also superior in the prediction stage. This model inherits the advantages of the Swin Transformer detection model and is superior to mainstream models such as Faster R-CNN and YOLOv5 in terms of the single particle detection capability of cryo-electron micrographs.

Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability.

BACKGROUND: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy. RESULTS: CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was - 11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about two time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth. CONCLUSIONS: Na2GA/CA-BM nanoparticles (131.6 nm, - 11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.

Tumor-targeting peptide functionalized PEG-PLA micelles for efficient drug delivery.

Because of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, block copolymer micelles are widely utilized for chemotherapy drug delivery. In order to further improve the anti-tumor ability and reduce unwanted side effects of drugs, tumor-targeting peptides were used to functionalize the surface of polymer micelles so that the micelles can target tumor tissues. Herein, we synthesized a kind of PEG-PLA that is maleimide-terminated and then conjugated with a specific peptide F3 which revealed specific capacity binding to nucleolin that is overexpressed on the surface of many tumor cells. Then, F3 conjugated, paclitaxel loaded nanoparticles (F3-NP-PTX) were prepared as stable micelles that displayed an enhanced accumulation via a peptide-mediated cellular association in human breast cancer cells (MCF-7). Furthermore, F3-NP-PTX showed a prominent anti-tumor efficacy compared with non-targeting nanoparticles (NP-PTX) both in vitro and in vivo, and showed great potential as an efficacious targeting drug delivery system for breast cancer treatment.

Preparation and Properties of Tumor-Targeting MRI Contrast Agent Based on Linear Polylysine Derivatives.

We developed a tumor-targeted contrast agent based on linear polylysine (PLL) by conjugating a small molecular imaging agent, fluorescent molecule and targeting agent amino phenylboronic acid onto the amino groups of polylysine, which can specifically target monosaccharide sialic acid residues overexpressing on the surface of tumor cell membranes. Further, 3,4,5,6-Tetrahydrophthalic anhydride (DCA) was attached to the free amino groups of the polylysine to change to a negative charge at physiology pH to lower the cytotoxicity, but it soon regenerated to a positive charge again once reaching the acidic intratumoral environment and therefore increased cell uptake. Laser confocal microscopy images showed that most of the polymeric contrast agents were bound to the cancer cell membrane. Moreover, the tumor targeting contrast agent showed the same magnetic resonance imaging (MRI) contrasting performance in vitro as the small molecule contrast agent used in clinic, which made it a promising tumor-targeting polymeric contrast agent for cancer diagnosis.