Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8+ T cell exhaustion and anti-PD-1 resistance.

Resistance to PD-1 blockade in onco-immunotherapy greatly limits its clinical application. T cell immunoglobulin and mucin domain containing-3 (Tim-3), a promising immune checkpoint target, is cleaved by ADAM10/17 to produce its soluble form (sTim-3) in humans, potentially becoming involved in anti-PD-1 resistance. Herein, serum sTim-3 upregulation was observed in non-small cell lung cancer (NSCLC) and various digestive tumors. Notably, serum sTim-3 is further upregulated in non-responding patients undergoing anti-PD-1 therapy for NSCLC and anti-PD-1-resistant cholangiocarcinoma patients. Furthermore, sTim-3 overexpression facilitates tumor progression and confers anti-PD-1 resistance in multiple tumor mouse models. Mechanistically, sTim-3 induces terminal T cell exhaustion and attenuates CD8+ T cell response to PD-1 blockade through carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). Moreover, the ADAM10 inhibitor GI254023X, which blocks sTim-3 production, reduces tumor progression in Tim-3 humanized mice and reverses anti-PD-1 resistance in human tumor-infiltrating lymphocytes (TILs). Overall, human sTim-3 holds great predictive and therapeutic potential in onco-immunotherapy.

Photocatalytic degradation of fluoranthene in soil suspension by TiO2/α-FeOOH with enhanced charge transfer capacity.

Polycyclic aromatic hydrocarbons (PAHs) in soil are potentially harmful to human health. However, the use of photocatalysis technology to treat soil contaminated with PAHs remains challenging. Therefore, TiO2/α-FeOOH composite photocatalyst has been synthesized by hydrothermal method and sol-gel method and applied to photocatalytic degradation of fluoranthene in soil. The morphology, elements, crystal structure, optical properties, electrochemical characteristics, and photocatalytic activity of TiO2/α-FeOOH have been characterized. Results showed that TiO2 is tightly fixed on the surface of α-FeOOH, and TiO2/α-FeOOH had higher photocatalytic activity on photocatalytic degradation of fluoranthene in soil under simulated sunlight. The degradation efficiency of TiO2/α-FeOOH is 3.0 and 4.8 times higher than that of TiO2 and α-FeOOH, respectively. This is attributed to enhanced photocatalytic ability by enhancing the transfer capacity of electrons and holes and broadening the spectrum absorption range. The highest degradation efficiency was achieved when the pH of the soil is neutral, the ratio of water/soil is 10:1, and the dosage of catalyst is 50 mg/g. In addition, it was proved that •O2-, h+, and 1O2 are the main active substances in the photocatalysis of TiO2/α-FeOOH. The possible mechanism of a Z-type electron transfer structure was also proposed. The degradation products of fluoranthene were detected, and the degradation pathway was deduced.

DNA nanostructure-based universal microarray platform for high-efficiency multiplex bioanalysis in biofluids.

Microarrays of biomolecules have greatly promoted the development of the fields of genomics, proteomics, and clinical assays because of their remarkably parallel and high-throughput assay capability. Immobilization strategies for biomolecules on a solid support surface play a crucial role in the fabrication of high-performance biological microarrays. In this study, rationally designed DNA tetrahedra carrying three amino groups and one single-stranded DNA extension were synthesized by the self-assembly of four oligonucleotides, followed by high-performance liquid chromatography purification. We fabricated DNA tetrahedron-based microarrays by covalently coupling the DNA tetrahedron onto glass substrates. After their biorecognition capability was evaluated, DNA tetrahedron microarrays were utilized for the analysis of different types of bioactive molecules. The gap hybridization strategy, the sandwich configuration, and the engineering aptamer strategy were employed for the assay of miRNA biomarkers, protein cancer biomarkers, and small molecules, respectively. The arrays showed good capability to anchor capture biomolecules for improving biorecognition. Addressable and high-throughput analysis with improved sensitivity and specificity had been achieved. The limit of detection for let-7a miRNA, prostate specific antigen, and cocaine were 10 fM, 40 pg/mL, and 100 nM, respectively. More importantly, we demonstrated that the microarray platform worked well with clinical serum samples and showed good relativity with conventional chemical luminescent immunoassay. We have developed a novel approach for the fabrication of DNA tetrahedron-based microarrays and a universal DNA tetrahedron-based microarray platform for the detection of different types of bioactive molecules. The microarray platform shows great potential for clinical diagnosis.