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Mutant p53(Mtp53) not only loses its canonical tumor-suppressive functions but also acquires oncogenic gain-of-function properties, positioning it as a central orchestrator in reshaping the tumor immune microenvironment. This review systematically delineates how Mtp53 actively establishes and sustains an immunosuppressive niche through multiple interconnected mechanisms, including chronic inflammation, immune cell dysfunction, reprogramming of cancer-associated fibroblasts, metabolic dysregulation, epigenetic hijacking, and potentially aberrant liquid–liquid phase separation, thereby promoting immune evasion and therapeutic resistance. We integrate current evidence to propose a conceptual “metabolism–epigenetics–immunity” axis: Mtp53-driven metabolic reprogramming—such as accumulation of lactate or α-ketoglutarate—can modulate chromatin modifications and immune gene expression. Notably, the full in vivo causal chain of this axis remains unestablished; existing support derives primarily from stepwise experimental data and strong correlations. The immunological impact of Mtp53 is highly context-dependent, shaped by co-mutations and tissue origin. In TP53/KRAS co-mutant non-small cell lung cancer (NSCLC), Mtp53 enhances tumor immunogenicity and improves response to immune checkpoint inhibitors (ICIs); conversely, in immunologically “cold” tumors—such as triple-negative breast cancer, pancreatic ductal adenocarcinoma, and colorectal cancer—it promotes T-cell exhaustion or myeloid suppression, reflecting marked cancer-type heterogeneity. Therapeutic approaches include Mtp53 reactivators (e.g., APR-246, PC14586), degraders, synthetic lethal strategies, and neoantigen vaccines. Although APR-246 showed efficacy in a phase II trial (NCT03072043), it failed to improve survival in phase III (NCT03745716) due to lack of TP53 mutation stratification. Its combination with pembrolizumab (NCT04383938) demonstrated acceptable safety (immune-related adverse events in ∼12%) but limited efficacy, underscoring the need for biomarker-guided, precision-based combinations. Thus, a multidimensional biomarker platform is urgently needed—one integrating TP53 mutation subtypes (e.g., R175H vs . nonsense mutations), dynamic ctDNA monitoring (VAF ≥ 0.01%), tumor immune microenvironment (TIME) features (e.g., TILs, MDSCs), and spatial multi-omics—to enable precise molecular stratification and personalized intervention in Mtp53-driven cancers.

This study comprises two meta-analyses conducted to investigate relations between socioeconomic status (SES) and academic achievement, with a focus on macro-level, micro-level, and methodological moderating variables in primary and secondary education. The first meta-analysis is based on 326 empirical studies with 949,699 students from 47 countries and areas, and the second is based on three international large-scale assessments (i.e., PISA, TIMSS, and PIRLS) with 1230 independent samples of 5,095,283 students from 105 countries and areas. We found moderate correlations between SES and academic achievement across the world, rs = .22 ~ .28. Moderation analyses revealed that (a) these relations have strengthened since the 1990s; (b) GDP per capita and economic equality did not affect the relations; (c) higher net enrollment ratio and longer duration of compulsory education did not weaken these relations; (d) the relations stayed stable or even strengthened across grades in concurrent and longitudinal designs. Taken together, our findings suggest that educational expansion that focuses on increasing educational opportunities does not seem to reduce inequalities in academic outcomes between high- and low-SES school children in educational systems on the national level. Quality indicators for educational expansion, however, should be considered in setting educational policy to achieve inclusive, equitable education.

AimsRecently, cancer-derived exosomes were shown to have pro-metastasis function in cancer, but the mechanism remains unclear. Angiogenesis is essential for tumor progression and is a great promising therapeutic target for advanced cervical cancer. Here, we investigated the role of cervical cancer cell-secreted exosomal miR-221-3p in tumor angiogenesis.Methods and resultsmiR-221-3p was found to be closely correlated with microvascular density in cervical squamous cell carcinoma (CSCC) by evaluating the microvascular density with immunohistochemistry and miR-221-3p expression with in situ hybridization in clinical specimens. Using the groups of CSCC cell lines (SiHa and C33A) with miR-221-3p overexpression and silencing, the CSCC exosomes were characterized by electron microscopy, western blotting, and fluorescence microscopy. The enrichment of miR-221-3p in CSCC exosomes and its transfer into human umbilical vein endothelial cells (HUVECs) were confirmed by qRT-PCR. CSCC exosomal miR-221-3p promoted angiogenesis in vitro in Matrigel tube formation assay, spheroid sprouting assay, migration assay, and wound healing assay. Then, exosome intratumoral injection indicated that CSCC exosomal miR-221-3p promoted tumor growth in vivo. Thrombospondin-2 (THBS2) was bioinformatically predicted to be a direct target of miR-221-3p, and this was verified by using the in vitro and in vivo experiments described above. Additionally, overexpression of THBS2 in HUVECs rescued the angiogenic function of miR-221-3p.ConclusionsOur results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression.

While the opening of the bond market provides strong support for high-level financial opening, it also accelerates the accumulation of systemic financial risks, thereby affecting the high-quality development of China’s finance. Based on data from 2003 to 2024, this paper measures China’s bond market opening, monetary policy, and systemic financial risks, and employs a TVP-SV-VAR model to investigate the time-varying relationships among bond market opening, monetary policy, and systemic financial risks. The findings are as follows: (1) The impact of bond market opening on China’s systemic financial risks exhibits time-varying characteristics; (2) Contractionary monetary policy helps curb systemic financial risks, but this effect marginally diminishes when facing external structural shocks; (3) The improvement of interest rate transmission mechanisms and the transition toward price-based monetary policy can significantly enhance the sustainability of monetary policy’s regulatory role in systemic financial risks; (4) There exists a significant linkage effect between bond market opening and monetary policy, but this effect is subject to time-varying influences from the progress of domestic institutional reforms and cross-border capital anomalies.

Background Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). Methods Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. Results CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. Conclusion Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors. Mild photothermal therapy can be used to induce a favourable immunological response. In this study, the authors combine a photothermal therapy sensitizer and anti-PD-L1 into a lipid gel and find that, on controlled delivery to tumours, it potentiates anti-PD therapy and boosts anticancer efficacy.

The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.

Recent decades have witnessed the huge successes of organic field‐effect transistors (OFETs) and their applications. Among them, OFET‐based sensors have shown promising applications in the field of food safety, industrial security, environmental, and health monitoring. This is due to their advantages in solution processability, flexibility, light weight, and variety in molecular design. This review highlights recent progress in OFET‐based chemical and biological sensors in gas and liquid phase, especially for the past 5 years. The analytes range from small molecules to large biomolecules. The optimizations of OFET devices for sensors, including the semiconducting layers, dielectric layers, electrodes, and their interfaces etc., are illustrated. And their relationships with sensing parameters (sensitivity, selectivity, and response time) as well as the sensing mechanisms are given. Finally, the remaining challenges are discussed. We expect that this review can offer inspiration for future design of OFET‐based sensors. OFET‐based sensors have shown promising applications in the field of food safety, industrial security, environmental, and health monitoring. This review highlights recent progress in OFET‐based chemical and biological sensors in gas and liquid phase, especially for the past 5 years.

Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to the existence of blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation to achieve BBB crossing and deep tumor penetration of drugs. Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid) (PDDA) and loaded with temozolomide and indocyanine green (ICG), the nanogels are inert to endogenous oxidative conditions but can be selectively disintegrated by ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation and active tumor targeting. The precisely controlled NIR irradiation on tumor lesions excites ICG and deforms the cumulated nanogels to trigger burst drug release for facilitated BBB permeation and infiltration into distal tumor cells. These NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic GBM and GBM stem cells-bearing mouse models with significantly extended survival. Effective drug accumulation in deep glioblastoma multiforme (GBM) lesions remains challenging due to the blood brain barrier. Here, the authors develop a biomimetic nanogel system activated by near infrared irradiation and show high efficacy in orthotopic GBM and GBM stem cells-bearing mouse models.