An analytical method was developed for the simultaneous extraction and determination of eighteen fluoroquinolones (FQs), tetracyclines (TCs) and sulfonamides (SAs) antibiotics from soils using solid phaseextraction and liquid chromatography tandem mass spectrometry.Soil sample was firstly extracted by phosphate buffer at pH 3 in combination with 50% of organic modifier acetonitrile, then purified and concentrated by SAX and HLB column.Qualitative and quantitative analysis were carried out for the analyte under the MRM mode after the chromatography separation on Kromasil C_(18)(250 mm x4.6 mm, 5 μm) column.The range of recoveries (in percent) for FQs, TCs, SAs, in the soil matrix was 67.20%-88.98%, 62.23%-85.36%, 55.76%-97.37% with 1.1%-17.2% of relative standard deviation respectively in two different concentra tions.The limits of quantification (LOQ, S/N = 3) were 3.36-8.88 jig/kg, 0.56-0.91 μg/kg and 0.07-1.85 μg/kg for FQs, TCs and SAs, respectively.This method was successfully used to detect 18 anti biotics in 6 soil samples with different land types in Tianjin.Results showed some of the antibiotics in the arable soil were detected, with concentrations of 1.72-119.57 μg/kg.

A rapid headspace gas chromatography tandem mass spectrometric ( HS-GC/MS ) method was established for the analysis of volatile fatty acids ( VFAs ) in the feces. Feces were suspended by 6%phosphoric acid aqueous solution (1:2 m/V) and sealed in the headspace bottle for HS-GC/MS analysis. The HS-GC/MS method was optimized as follows: agitator temperature ( temp. ):80 ℃, syringe temp.:80 ℃, sample incubation time: 30 min, injection: 1 mL without split-flow. The chromatographic separation was performed on a DB-FFAP capillary column (30m×0. 25 mm×0. 25 μm) with injection port temp.:250 ℃. The temperature program ( initial temp. at 50 ℃ within first 1 min, and raised to 200 ℃ by 10 ℃/min) was employed by fixing the flow of carrier gas (high purity helium) at 1. 0 mL/min. The electron energy at -70 eV for electron impact ( EI ) ionization, ion source temp.: 250 ℃, transfer line temp.:280 ℃, the voltage of electron multiplier at 0. 95 kV. The spectra were recorded in the range of m/z 33-200 for full scan. The established HS-GC/MS method could be applied to analyze VGAs in the feces from human and rat appropriately. There are nine VFAs identified in the feces from human, and eight VFAs detected in the feces from rat by retrieving the NIST library, comparing with the standards and analyzing the MS data. Furthermore, the relative percentage contents of acetic acid, propionic acid and butyric acid accounted for roughly 85% of all VFAs by area normalization. The method is simple and sensitive, and it can be used to rapidly detect VFAs in the feces from human and rat.

Cancer immunotherapy has veered the paradigm of cancer treatment. Despite recent advances in immunotherapy for improved antitumor efficacy, the complicated tumor microenvironment (TME) is highly immunosuppressive, yielding both astounding and unsatisfactory clinical successes. In this regard, clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME. Various advanced designs of nanomedicines could still not fully surmount the delivery barriers of the TME. The immunosuppressive TME may even dampen the efficacy of antitumor immunity. Recently, some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment (TIME) for robust immunotherapeutic responses. In this review, we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy, especially those unique classes associated with the immunosuppressive effect. The immunoregulatory cell types inside the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation. After introducing the various strategies, we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nanomedicines.

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.