Jian Wang

Objective CircRNAs are involved in cancer progression. However, their role in immune escape in non-small cell lung cancer (NSCLC) remains poorly understood. Methods This study employed RIP-seq for the targeted enrichment of circRNAs, followed by Western blotting and RT-qPCR to confirm their expression. Specific binding was assessed using electrophoretic mobility shift assays. Transwell and wound healing assays were performed to evaluate the invasive and migratory capacities of NSCLC cells. The secretion of TNF-α, IFN-γ, GzmB, and perforin by CD8⁺ T cells co-cultured with peripheral blood mononuclear cells (PBMCs) was quantitatively measured using enzyme-linked immunosorbent assays. The PD-L1 phenotype and apoptosis levels were determined by flow cytometry, while cell proliferation and apoptosis were evaluated through CCK-8, EdU, and TUNEL assays. The in vivo role of circ_0074158 was investigated using a mouse subcutaneous tumour implantation model. Results QKI6 modulates the level of PD-L1 ubiquitination in NSCLC. Both hsa_circ_0074158 and QKI6 influence the proliferation, invasion, and migration of NSCLC cells. Circ_0074158 regulates PD-L1 ubiquitination by modulating QKI6 expression, thus affecting PD-L1 expression. Furthermore, circ_0074158 activates CD8⁺ T cells in PBMCs, inhibits immune escape, and promotes tumour cell apoptosis, suppressing tumour growth. Conclusion The circ_0074158/QKI6 axis regulates PD-L1 ubiquitination in NSCLC, limiting tumour cell proliferation and invasion. Our findings reveal a novel function for circ_0074158 in NSCLC, suggesting its potential as a therapeutic target.

Background: Non-small cell lung cancer (NSCLC) is the predominant histological subtype of lung cancer, whose diverse genomic landscape complicates prognosis and outcome prediction. In this context, immunogenic cell death (ICD), a distinct mechanism of cell death, may exert important antitumor effects. However, the specific role of ICD in NSCLC has not been clarified, and there is no suitable method for using ICD to achieve the treatment and prognosis assessment of NSCLC. The purpose of the current research is to develop a new approach to predict the survival prognosis and response to chemotherapy and targeted therapy in patients with NSCLC. Methods: We used 101 combinations of 10 machine learning algorithms to construct an ICD-related signature (ICDRS). The predictive potential of this specific ICDRS for immune cell infiltration and therapeutic response was evaluated. We also examined the molecular mechanisms underlying the various responses of different ICDRS subpopulations, characterized the mutational landscape and tumor mutational burden (TMB), and assessed the applicability of the ICDRS in single-cell transcriptomic datasets. Gene expression patterns were subsequently validated with quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results: We screened out five key ICDRS genes (MMP14, ALDH2, FBP1, HLA-DRA, KCTD12). Patients were classified into high-risk and low-risk groups according to the ICDRS score determined by the expression levels of these five genes. The high-risk group exhibited less favorable prognoses compared with the low-risk group, which demonstrated more positive outcomes. The low-risk group had more anticancer immune-cell infiltration and showed better response to chemotherapy and targeted therapy than the high-risk group (PConclusions: The ICDRS exhibited excellent predictive performance and broad applicability, suggesting it as a powerful tool for prognosis and therapy response. The current study may contribute to more adequate patient selection in the context of tailored therapies.

Objective: The present retrospective cohort study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy for resectable esophageal cancer and report the preliminary short-term survival. Methods: A multicenter, retrospective study was conducted concerning patients who received neoadjuvant PD-1 agents plus platinum-based chemotherapy between January 2019 and January 2022. The primary endpoint was the tumor pathologic complete response (pCR) rate. Results: Two hundred and thirteen patients with initial stage cI-IVA esophageal cancer who received neoadjuvant immunochemotherapy were identified. The complete tumor resection(R0) rate was 99.1%. The pCR rate was 31.9%, and the overall major pathological response rate was 49.8%. The 2-year DFS rate was 78.9% (95% CI: 72.9–85.4%) and the 2-years OS rate was 80.9% (95% CI: 75.3–86.9%). The incidence of TRAEs and surgical complications rate were 68.5 and 35.2%, respectively. Conclusion: The PD-1 agents combined with chemotherapy in the neoadjuvant treatment for resectable stage I–IVA esophageal cancer had a high pCR rate as well as good short-term survival benefits and tolerable toxicity.

Clinical benefit of neoadjuvant immunotherapy in resectable esophageal squamous cell carcinoma (ESCC). remains unclear. This study evaluated the efficacy and safety of the programmed death 1 (PD-1) inhibitor tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable ESCC. Treatment-naïve patients were enrolled and eligible patients received 3 cycles of neoadjuvant therapy with tislelizumab, carboplatin, and nab-paclitaxel. The primary endpoint was surgery patients major pathological response (MPR). Subgroup analysis was stratified by tumor downstaging, circumferential resection margin (CRM), PD-ligand 1 (PD-L1) expression, and tumor mutation burden (TMB). Safety was assessed by adverse events (AEs) and postoperative complications. Between September 2020 and March 2021, 45 patients were enrolled. Thirty-six (80.0%) of 45 patients underwent surgery, and 29 (80.5%) underwent successful R0 resection. MPR and pathological complete response (pCR) for surgery patients were 72.0% and 50.0%, respectively. Intention to treatment (ITT) patients MPR and PCR were 57.5% and 40%. Downgrading occurred in 75% of 36 patients. MPR and pCR were identified to be associated with tumor downstaging and CRM but not PD-L1 expression or TMB. TPS levels in MPR and pCR group were significantly higher than that in Non-MPR and Non-pCR group, respectively. Treatment-related AEs of grade 3-4 and immune-related AEs occurred in 42.2% and 22.2% of 45 patients, respectively, and postoperative complications occurred in 77.8% of 36 patients. No treatment-related surgical delay or death occurred. No associations between gene mutation and pathological efficacy were observed. Tislelizumab plus chemotherapy as neoadjuvant therapy demonstrates promising antitumor activity for resectable ESCC with high rates of MPR, pCR, and R0 resection, as well as acceptable tolerability.

The adsorption process of MIPs to template molecule invisible, and biomacromolecule MIPs easily contaminated by bacteria have become the key factor of restricting MIPs applications. In this work, the novel BSA-MIPs with visualized adsorption efficiency and antibacterial ability were prepared by ATRP. The results showed that the BSA-MIPs could adsorb BSA specifically through homogeneous imprinted holes and had excellent antibacterial properties in the process of separation BSA from blood plasma.

With the increase in antibiotic resistance, the development of new antibacterial agents is urgent. Photosensitizers with no detectable resistance are promising antibacterial agents. However, most photosensitizers are insoluble, structurally unstable and ineffective against Gram-negative bacteria due to their negatively charged cell wall that hinder their use. In this study, a novel bacteria-activated photosensitizer ionic liquid was designed and assembled to improve the solubility, stability and antibacterial ability of photodynamic therapy. The cation 1-vinyl-3-dodecyl imidazole has been designed, which has strong binding energy with the major constituent of the cell wall. The anion selected was chlorin e6 (Ce6) since it could respond to the acidic microenvironment of bacterial infection. The Ce6 ionic liquid (Ce6-IL) composed of 1-vinyl-3-dodecyl imidazole and Ce6 not only exhibited bacteria-activated ability because its cation could firmly bond with peptidoglycan in the cell wall, but also had excellent acid responsive ability due to the protonation reaction of COO⁻ in its anion. The binding energy of the cation with peptidoglycan was calculated via molecular dynamics simulation, and the pH-responsive behavior of Ce6-IL was verified via HR-MS. The surface potential, mechanical property, morphology and uptake rate results indicated that the cation could destroy the cell wall and promote the anion Ce6 to enter the bacteria. Due to the dual-mode antibacterial action of its cation and anion, Ce6-IL was more effective against Gram-negative and Gram-positive bacteria than Ce6 alone and had wide-spectrum antibacterial ability. The in vitro studies showed that the IC₅₀ of Ce6-IL against E. coli and S. aureus was reduced by 100 and 10 times, respectively. Furthermore, the in vivo studies indicated that Ce6-IL was more effective for eliminating bacterial infection and could accelerate wound healing. The compatibility test showed that Ce6-IL had low toxicity and exhibited excellent biocompatibility.