Liquid Metal Nanoplatform Based Autologous Cancer Vaccines.

Therapeutic cancer vaccines have been vigorously sought to bolster host adaptive immunity against metastatic cancers, but tumor heterogeneity, ineffective antigen utilization, and immunosuppressive tumor microenvironment hinder their clinical applications. Autologous antigen adsorbability and stimulus-release carrier coupling with immunoadjuvant capacity are urgent for personalized cancer vaccines. Here, we propose a perspective strategy of using a multipotent gallium-based liquid metal (LM) nanoplatform for personalized in situ cancer vaccines (ISCVs). The antigen-capturing and immunostimulatory LM nanoplatform can not only effectively destroy orthotopic tumors to generate multifarious autologous antigens upon external energy stimulation (photothermal/photodynamic effect) but also capture and transport antigens into dendritic cells (DCs) to enhance antigen utilization (adequate DCs uptake, antigen-endo/lysosomal escape) and facilitate DCs activation (mimic alum immunoadjuvant capacity), which ultimately awaken systemic antitumor immunity (expand cytotoxic T lymphocytes and modulate tumor microenvironment). With immune checkpoint blockade (anti-PD-L1) to further relieve the immunosuppressive tumor microenvironment, the positive tumoricidal immunity feedback loop was established to effectively eliminate orthotopic tumors, inhibit abscopal tumor growth, relapse, and metastasis as well as tumor-specific prevention. Collectively, this study demonstrates the potential of a multipotent LM nanoplatform for personalized ISCVs, which will open frontier exploration of LM-based immunostimulatory biomaterials and may encourage further investigation of precise individualized immunotherapy.

Pathogenic sphingosine 1-phosphate pathway in psoriasis: a critical review of its pathogenic significance and potential as a therapeutic target.

Sphingosine-1-phosphate (S1P) is a sphingolipid mediator that exerts a variety of biological functions, including immune, cardiovascular, and neurological regulation as well as tumor promotion, through high-affinity G protein-coupled receptors (S1P1-5). It has been reported that circulating S1P levels remain higher in patients with psoriasis than in healthy individuals and that circulating S1P levels do not decrease after anti-TNF-α treatment in those patients. The S1P-S1PR signaling system plays an important role in inhibiting keratinocyte proliferation, regulating lymphocyte migration, and promoting angiogenesis, thus contributing to the regulation of psoriasis pathogenesis. Here, we review the mechanisms by which S1P-S1PR signaling affects the development of psoriasis and the available clinical/preclinical evidence for targeting S1P-S1PR in psoriasis. S1P-S1PR signaling mechanisms may partially explain the link between psoriasis and its comorbidities. Although the detailed mechanisms remain to be elucidated, S1P may be a new target for future psoriasis remission.

Autologous-cancer-cryoablation-mediated nanovaccine augments systematic immunotherapy.

Cancer vaccines developed from autologous tumors hold tremendous promise for individualized cancer immunotherapy. Cryoablation-induced in situ autologous antigens are capable of activating systemic immunity with low damage. However, the dissipation of cancer fragments after cryoablation induces poor immunogenicity and short-time maintenance of immunological memory. To solve this challenge, a nanovaccine with functional grippers is proposed to largely enhance the in situ grasping of tumor fragments, combined with an immune adjuvant to further strengthen the immune-therapeutic effect. Herein, maleimide-modified Pluronic F127-chitosan nanoparticles encapsulating Astragalus polysaccharide (AMNPs) are developed. The AMNPs can capture multifarious and immunogenic tumor antigens generated through cryoablation, specifically target lymph nodes and facilitate lysosome escape to activate remote dendritic cells, and modulate T cell differentiation through cross-presentation, thereby breaking the immunosuppressive microenvironment to achieve durable and robust tumor-specific immunity. In the bilateral Lewis lung cancer tumor model, AMNP-mediated cryoablation can significantly regress primary tumors (with a tumor growth inhibition rate of 100%, and a recurrence rate of 0% (30 days) and 16.67% (60 days)), inhibit untreated abscopal tumor growth (a decrease of about 3.84-fold compared with the saline group), and ultimately improve the long-term survival rate (83.33%). Collectively, the development of a lymph-node-targeted in situ cancer-cryoablation-mediated nanovaccine provides a promising approach for personalized cancer immunotherapy against metastatic cancers.

Rigid metal/liquid metal nanoparticles: Synthesis and application for locally ablative therapy.

Locally ablative therapy, as the main therapy for advanced tumors, has fallen into a bottleneck in recent years. The breakthrough of metal nanoparticles provides a novel approach for ablative therapy. Previous studies have mostly focused on the combined field of rigid metal nanoparticles and ablation. However, with the maturity of the preparation process of liquid metal nanoparticles, liquid metal nanoparticles not only have metallic properties but also have fluid properties, showing the potential to be combined with ablation. At present, there is no review on the combination of liquid metal nanoparticles and ablation. In this article, we first review the preparation, characterization and application characteristics of rigid metal and liquid metal nanoparticles in ablation applications, and then summarize the advantages, disadvantages and possible future development trends of rigid and liquid metal nanoparticles.

[Preparation of magnetic surface molecularly imprinted polymers for melamine and its application in milk samples].

By using melamine (MEL) as the template molecule, magnetic surface molecularly imprinted polymers (MMIPs) were prepared. Methacrylic acid (MAA) was chosen as the functional monomer, and ethyleneglycol dimethacrylate (EGDMA) was chosen as the cross-linker, and Fe3O4@SiO2 was used as the magnetic supporter. Transmission electron microscope (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) analysis and a vibrating sample magnetometer (VSM) were used to characterize the polymers. An imprinted polymer layer was found on the surface of the Fe3O4@SiO2 nanomaterials. MMIPs were applied to extract and enrich melamine in milk samples. The specific recognition capability of the material was confirmed by high performance liquid chromatographic (HPLC) analysis. Thus, a simple and selective method was successfully established using MMIPs as sorbents to detect melamine in milk with satisfactory results.

Assessment on Occurrences of Depression and Anxiety and Associated Risk Factors in the Infertile Chinese Men.

The prevalence of depression and anxiety in the Chinese male population with infertility is still uncertain. The prevalence of depression, anxiety, and a combination of both psychological symptoms was 20.8%, 7.8%, and 15.4%, respectively in 771 infertile Chinese men in the current study by the Mental Health Inventory-5 and the State-Trait Anxiety Inventory-Short Form questionnaires. Differences in demographics (age, education, and income) had no noticeable impact on the development of psychological symptoms. Clinical factors such as concomitant disorders (varicocele, epididymal cyst, and erectile dysfunction) were identified as risk factors associated with depressive symptoms ( OR = 1.47; 95% CI [1.14, 1.90]; p < .001) and both depressive and anxiety symptoms ( OR = 1.56; 95% CI [1.17, 2.08]; p < .001). An infertility duration over 2 years was associated with a high risk of anxiety symptoms ( OR = 3.94; 95% CI [1.20, 12.93], p < .02). Other clinical conditions such as type of treatment and quality of sperm were not significant risk factors for psychological symptoms. This study provides evidence that Chinese men of reproductive age who suffer from infertility are vulnerable to psychological distress.

Detection of MMP-9 and TIMP-3 mRNA expression in the villi of patients undergoing early spontaneous abortion: A report of 30 cases.

The aim of the present study was to investigate the correlation of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-3 expression with spontaneous abortion (SA) during early pregnancy. The villus tissues of 30 SA cases and 20 requested abortion cases were collected during surgery and constituted the SA and normal abortion (NA) groups, respectively. The total villous RNA was extracted and the expression levels of MMP -9 and TIMP-3 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay to calculate the MMP-9/TIMP-3 mRNA ratio. The MMP-9 mRNA expression level and MMP-9/TIMP-3 mRNA ratio of the SA group were significantly higher than those of the NA group (P<0.01), while the TIMP-3 mRNA levels of the two groups were similar (P>0.05). The MMP-9 mRNA expression level of the SA group was higher than that of the NA group; thus, the MMP-9/TIMP-3 mRNA ratio was higher. These results suggest that the expression level of MMP-9 mRNA and the MMP-9/TIMP-3 mRNA ratio are associated with SA.

[Preparation and applications of 4-methyl imidazole magnetic surface molecularly imprinted polymers].

The magnetic surface molecularly imprinted polymers (MIPs) with specific recognition of 4-methyl imidazole (4-MI) were prepared by using 4-MI as template molecule, methacrylic acid (MAA) as functional monomer and Fe3O4 as magnetic fluid. The polymers were characterized by of Fourier transform infrared spectrometer (FT-IR) analysis, X-ray diffraction (XRD) analysis, transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The results demonstrated that an imprinted polymer layer was successfully coated onto the surface of modified Fe3O4 nanomaterials, resulting in a narrow diameter distribution and good magnetic responsibility. The ultraviolet (UV) spectrophotometry was used to demonstrate the interaction between 4-MI and MAA. It was found that one 4-MI molecule was entrapped by one MAA molecule, which was the main existing form of subject and object. By UV spectrophotometric method to study the adsorption performance of magnetic molecularly imprinted polymers, the specific adsorption equilibrium and selectivity were evaluated by batch rebinding studies. The Scatchard analysis showed that there were two kinds of binding sites in the Fe3O4 @ (4-MI-MIP). The corresponding maximum adsorption capacities of 4-MI onto Fe3O4 @ (4-MI-MIP) were 40.31 mg/g and 23.07 mg/g, and the dissociation constants were 64.85 mg/L and 30.41 mg/L, respectively. The kinetic experimental data were correlated with second-order kinetic model. The magnetic molecularly imprinted polymers were used for the adsorption of 4-methyl imidazole in environmental water samples, and good results were obtained.