Current research status and development prospects of embolic microspheres containing biological macromolecules and others.

Transcatheter arterial embolization (TACE) has been used in the treatment of malignant tumors, sudden hemorrhage, uterine fibroids, and other diseases, and with advances in imaging techniques and devices, materials science, and drug release technology, more and more embolic agents that are drug-carrying, self-imaging, or have multiple functions are being developed. Microspheres provide safer and more effective therapeutic results as embolic agents, with their unique spherical appearance and good embolic properties. Embolic microspheres are the key to arterial embolization, blocking blood flow and nutrient supply to the tumor target. This review summarizes some of the currently published embolic microspheres, classifies embolic microspheres according to matrix, and summarizes the characteristics of the microsphere materials, the current status of research, directions, and the value of existing and potential applications. It provides a direction to promote the development of embolic microspheres towards multifunctionalization, and provides a reference to promote the research and application of embolic microspheres in the treatment of tumors.

Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling.

Dysregulation of MOF (also known as MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not catalytically inactive mutant (MOF-E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and deubiquitinates MOF at lysine 410, which protects it from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription in a JUN-dependent manner, which subsequently activates Wnt/ß-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies.

Immunotherapy is a new type of tumor treatment after surgery, radiotherapy and chemotherapy, and can be used to manage and destroy tumor cells through activating or strengthening the immune response. Immunotherapy has the benefits of a low recurrence rate and high specificity compared to traditional treatment methods. Immunotherapy has developed rapidly in recent years and has become a research hotspot. Currently, chimeric antigen receptor T-cell immunotherapy and immune checkpoint inhibitors are the most effective tumor immunotherapies in clinical practice. While tumor immunotherapy brings hope to patients, it also faces some challenges and still requires continuous research and progress. Combination therapy is the future direction of anti-tumor treatment. In this review, the main focus is on an overview of the research progress of immune checkpoint inhibitors, cellular therapies, tumor vaccines, small molecule inhibitors and oncolytic virotherapy in tumor treatment, as well as the combination of immunotherapy with other treatments.

Effective Strategies for Developing Potent, Broad-Spectrum Antibacterial and Wound Healing Promotion from Short-Chain Antimicrobial Peptides.

Traumatic multidrug resistant bacterial infections are the most lethal threat to wound healing. Antimicrobial peptides have been widely used in the antimicrobial field for their good biocompatibility and resistance to multidrug-resistant bacteria. In this work, bacterial membranes of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were extracted and immobilized on homemade silica microspheres to make a bacterial membrane chromatography stationary phase in order to quickly screen for peptides with antibacterial effects. The antimicrobial peptide was then successfully screened using bacterial membrane chromatography from a library of peptides synthesized by the one-bead-one-compound method. The antimicrobial peptide was effective in better shielding both Gram-positive and Gram-negative bacteria. Based on this antimicrobial peptide (RWPIL), we have developed an antimicrobial hydrogel with a backbone of this antimicrobial peptide and oxidized dextran (ODEX). Owing to the interlinkage between the aldehyde group in oxidized dextran and the amine group from the trauma tissue, the hydrogel extends over the irregular obverse of the skin defect and promotes epithelial cell adhesion. Based on the histomorphological analysis, we confirmed that the RWPIL-ODEX hydrogel exerts a powerful therapeutic effect in a wound infection model. In conclusion, we have developed a new antimicrobial peptide, RWPIL, and a hydrogel based on the peptide that kills multidrug-resistant bacteria parasitic on wounds and promotes wound healing.

Preparation of thrombin-loaded calcium alginate microspheres with dual-mode imaging and study on their embolic properties in vivo.

Transcatheter arterial embolization (TAE) has played a huge role in the interventional treatment of organ bleeding and accidental bleeding. Choosing bio-embolization materials with good biocompatibility is an important part of TAE. In this work, we prepared a calcium alginate embolic microsphere using high-voltage electrostatic droplet technology. The microsphere simultaneously encapsulated silver sulfide quantum dots (Ag2S QDs) and barium sulfate (BaSO4), and fixed thrombin on its surface. Thrombin can achieve an embolic effect while stopping bleeding. The embolic microsphere has good near-infrared two-zone (NIR-II) imaging and X-ray imaging effects, and the luminous effect of NIR-II is better than that of X-rays. This breaks the limitations of traditional embolic microspheres that only have X-ray imaging. And the microspheres have good biocompatibility and blood compatibility. Preliminary application results show that the microspheres can achieve a good embolization effect in the ear arteries of New Zealand white rabbits, and can be used as an effective material for arterial embolization and hemostasis. This work realizes the clinical embolization application of NIR-II combined with X-ray multimodal imaging technology in biomedical imaging, achieving complementary advantages and excellent results, more suitable for studying biological changes and clinical applications.

Yolk-shell Co3 O4 @Fe3 O4 /C Nanocomposites as a Heterogeneous Fenton-like Catalyst for Organic Dye Removal.

The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites with Co3 O4 as the core, Fe3 O4 /C as the shell, and a cavity structure were synthesized by the hard template method. The physical and chemical properties of the composites were characterized by SEM, TEM, XRD, TGA, XPS, BET, and VSM. The specific surface area of yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites is 175.9 m2  g-1 , showing superparamagnetic properties. The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites were used as heterogeneous Fenton catalysts to activate peroxymonosulfate (PMS) to degrade MB, which showed high catalytic degradation performance. The degradation rate of MB reached 100 % within 30 min under the circumstances of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites dosage of 0.1 g L-1 , the PMS dosage of 1.0 g L-1 , the initial MB concentration of 100 mg L-1 , an initial pH of 5.5, and a temperature of 30±2 °C. The enhanced catalytic performance of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be attributed to the synergistic effect of the two catalytically active materials and the middle cavity. The effects of different operating parameters and co-existing anion species on MB degradation were also investigated. Electron paramagnetic resonance (EPR) analysis and quenching experiments confirmed that the formation of SO4 ⋅- in the yolk-shell Co3 O4 @Fe3 O4 /C/PMS system contributes to MB degradation. In addition, yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be easily separated from the pollutant solution under the action of an external magnetic field, and the degradation rate of MB can still reach 98 % after five cycles, indicating that it has good stability and reusability and has broad application prospects in the field of water purification.

Delivery process and effective design of vectors for cancer therapy.

In recent years, the efficacy of nano-drugs has not been significantly better than that of the drugs themselves, mainly because nano-drugs enter the tumor vasculature, stay near the blood vessels, and cannot enter the tumor tissues or tumor cells to complete the drug delivery process. Although intratumor injection can significantly decrease this risk, the side effects are strong. The advent of drug delivery carrier materials offers an opportunity to avoid the side effects of systemic drug delivery and the damage caused by tumor resection, holding great promise for the future of cancer therapy. Here, we systematically review recent research advances in the classification of drug delivery carrier materials and the delivery process in drug delivery systems. This review is divided into several main sections, first, we summarize the classification of tumor drug carrier materials, including drug delivery vectors and gene delivery vectors, etc., which are introduced in detail, respectively. Then we describe the carrier materials to deliver the drug cascade and the transition pathways for drug delivery, including stabilization transitions, charge inversions, and size changes. Finally, we discuss the current design strategies and research progress of drug vectors and provide a summary and outlook. This review aims to summarize different drug delivery vehicles and delivery processes to provide ideas for effective cancer therapy.

Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2.

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.