Zhiwei Miao

T cells are the central effectors of antitumor immunity, yet their function is profoundly constrained by the metabolically hostile tumor microenvironment (TME). In order to meet the bioenergetic and biosynthetic demands of activation and differentiation, T cells undergo metabolic reprogramming, particularly enhanced glycolysis, upon antigen recognition. However, intratumoral glucose deprivation and lactate accumulation driven by the Warburg effect of cancer cells create a metabolic tug-of-war that differentially impacts T cell subsets. The present review systematically elucidates how glycolytic metabolism governs the fate and function of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells (Tregs), and CAR-T cells within the TME. It highlights the striking metabolic dichotomy between effector T cells that depend on aerobic glycolysis and Tregs, which exhibit metabolic plasticity enabling them to thrive under nutrient-limited conditions. Key signaling nodes, including calcium-NFAT, CD38/NAD⁺/SIRT1, MAPK/AP1, and PI3K/Akt/mTOR, converge to integrate microenvironmental cues with transcriptional and epigenetic programs that shape T cell immunity. The report also discusses how shared metabolic mechanisms intersect with synthetic receptor architecture to influence persistence and exhaustion in CAR-T cells. By exploring recent advances, this review aims to provide a framework for targeting glucose metabolism to enhance antitumor immune responses and optimize next-generation immunotherapies.

Stimulus-responsive sonodynamic immunotherapy is a promising non-invasive strategy that combines ultrasound-activated Sonodynamic therapy (SDT) with a smart stimulus-responsive nanodelivery system to overcome the limitations of traditional cancer therapies. By utilizing signals from the tumor microenvironment (TME), such as acidic pH, high glutathione (GSH) levels, enzyme overexpression, and hypoxia, stimulus-responsive nanosonic sensitizers enable precise, on-demand release and deep tumor penetration. Ultrasound activation generates reactive oxygen species (ROS) and cavitation effects, inducing immunogenic cell death (ICD), characterized by damage-associated molecular patterns (DAMPs) and exposure/release of tumor-associated antigens (TAAs). This approach can transform “cold” tumors into “hot” tumors, promoting dendritic cell maturation, cytotoxic T lymphocyte (CTL) infiltration, and systemic antitumor immunity, including remote effects and long-term immune memory. When combined with immune checkpoint blockade (ICB), chemodynamic therapy (CDT), gas therapy, photothermal (PTT)/photodynamic therapy (PDT), or gene therapy, stimulus-responsive sonodynamic immunotherapy can significantly improve tumor suppression rates, reduce metastasis, and minimize systemic toxicity. Despite significant progress in preclinical studies, clinical translation still faces numerous challenges, including low ICD efficiency in hypoxic tumors, TME heterogeneity, parameter standardization, and optimization of the dual role of High migration group box 1 (HMGB1). This review summarizes the mechanisms, stimulus-response strategies, multimodal synergistic effects, and current clinical progress of stimulus-responsive sonodynamic immunotherapy, highlighting its opportunities and key challenges in future precision cancer treatment.

Lipid metabolism reprogramming is one of the most prominent characteristics of cancer, but it is still unclear which regulatory pathways underlie this process in cancer cells. Circular RNAs (circRNAs) represent a novel category of non‐coding RNAs with multifaceted regulatory functions. While the biological roles of circRNAs in cancer have been elucidated, there remains a dearth of knowledge regarding their involvement and regulatory mechanisms in lipid metabolism within the context of cancer. This article provides an overview of the regulatory roles and specific mechanisms of circRNAs in cancer lipid metabolism reprogramming. By elucidating these mechanisms, it enhances our comprehension of the metabolic rewiring driving tumour development and uncovers new avenues for targeted therapy.

The global incidence of inflammatory bowel disease (IBD) continues to rise, yet its precise pathogenesis remains incompletely understood. In recent years, various gut microbiota-derived metabolites have been implicated in the development of IBD. Among them, succinic acid is a key metabolite produced by intestinal flora and serves as a central intermediate in the tricarboxylic acid (TCA) cycle, which plays a pivotal role in the IBD pathogenesis by modulating the intestinal mucosal barrier function, immune-metabolic reprogramming and cellular energy homeostasis. Abnormal succinate metabolism has also been linked to a range of metabolic disorders, including hepatitis, arthritis, diabetes mellitus, and cardiovascular diseases. Recently, its role in IBD has attracted growing interest. This review systematically elucidates the mechanisms by which succinate promotes pro-inflammatory immune phenotypes through a multifaceted network involving macrophage polarization, T-cell metabolic reprogramming, and epithelial-immune cell interactions, largely mediated via the SUCNR1 signaling axis. Furthermore, we explore the therapeutic potential of targeting succinate metabolism, offering new insights into IBD prevention and treatment.

Cholesterol metabolism reprogramming helps tumor cells meet their high energy and biosynthetic needs. Many studies link high cholesterol levels to a higher risk of cancers, such as breast, prostate, and colorectal cancer. Dysregulated cholesterol metabolism contributes to cancer development and progression. Various non-coding RNAs (ncRNAs), such as miRNAs, lncRNAs, circRNAs, piRNAs, and tRNAs, are key players in this process. However, systematic reviews of ncRNAs’ functions in cholesterol metabolism and their impact on tumor progression are limited. This review aims to address this gap by summarizing the current understanding of how ncRNAs govern cholesterol metabolism in cancer. We provide a comprehensive overview of cholesterol metabolism reprogramming in tumor progression through its influence on growth, metastasis, drug resistance, and immune evasion. Moreover, we summarize recent advances in understanding how ncRNAs regulate cholesterol metabolism in cancer, highlighting potential therapeutic targets for cancer treatment.

Background and Aim: Sanguisorba officinalis L. and Sophora japonica L. (SOSJ) have been frequently used as medicinal pairs for treating ulcerative colitis (UC) due to their hemostatic properties. However, the mechanisms underlying their therapeutic effects remain unclear. This study aims to predict the targets of SOSJ for UC treatment using liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry (LC‐QTOF‐MS) and network pharmacology.Methods: The efficacy of SOSJ was evaluated using a 3% dextrose sodium sulfate (DSS)‐induced UC mice model. The general condition of the mice, histopathology, and expression of colonic inflammatory factors were assessed. Additionally, the effect of SOSJ on angiogenesis was evaluated by detecting the mRNA of colonic angiogenesis‐related mediators, measuring microvessel density, and using transmission electron microscopy.Results: SOSJ significantly attenuated inflammation and inhibited pathological angiogenesis in UC mice. It alleviated weight loss, colon shortening, and the presence of pus and blood in stools. SOSJ also reduced the mRNA expression levels of IL‐6, IL‐1β, TNF‐α, VEGF, VCAM1, Ang1, MMP1, MMP2, and MMP9. Furthermore, SOSJ decreased the protein expression of the PI3K‐Akt pathway, an effect that could be reversed by 740Y‐P, a specific PI3K activator.Conclusion: S. officinalis L. and S. japonica L. exert therapeutic effects on mice with ulcerative colitis, potentially through the modulation of angiogenesis and the PI3K‐Akt signalling pathway.

Background: The interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis.Methods: Two-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran’s Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs.Results: We identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora.Conclusion: The present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

Background: The association between Gastroesophageal reflux disease (GERD) and oral symptoms has been reported in observational studies, but the causality of GERD to oral symptoms remained unknown. We aimed to assess the causal effect of GERD on five oral symptoms (mouth ulcers, toothache, loose teeth, bleeding gums, and periodontitis) using the two-sample Mendelian randomization (MR) method.Methods: Summary-level statistics for GERD and five oral symptoms were obtained from large-scale genome-wide association studies. Rigorous quality control of genetic instruments was conducted before MR analysis. Several analytical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, maximum likelihood, and robust adjusted profile score (RAPS) were utilized, and the results of IVW were taken as the main results. The MR-Egger intercept test, Cochran’s Q test, and leave-one-out test were used as sensitivity analysis for quality control.Results: After Bonferroni, IVW detected a significant effect of GERD on mouth ulcers (OR = 1.008, 95% CI = 1.003–1.013, p = 0.003), loose teeth (OR = 1.009, 95% CI = 1.005–1.012, p = 9.20 × 10⁻⁷), and periodontitis (OR = 1.229, 95% CI = 1.081–1.398, p = 0.002). Consistent patterns of associations were observed across several MR models and sensitivity analysis found little evidence of bias. Nominal significant associations were observed in toothache and bleeding gums (p < 0.05), and heterogeneity was detected.Conclusion: Our MR analyses supported the positive causal effect of GERD on oral symptoms, especially for mouth ulcers, loose teeth, and periodontitis. Our findings might shed light on the mechanism of oral disease and might imply that oral care should be enhanced in patients with GERD.

Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNB...