In biomedical research, understanding the heterogeneity in nanoparticle association among different cell populations is crucial for translating to efficacy and immune identification. Using time-of-flight mass cytometry (CyTOF), we quantitatively assessed the association and distribution of gold nanoparticles (AuNPs) in murine breast cancer 4T1 cells and various immune cell populations in whole blood. Our findings reveal significant variability in gold nanoparticle accumulation across different cell types. In vitro, 4T1 cells co-cultured with 0.1 nM AuNPs had a median gold mass of 0.214 pg per cell which increased proportionally and significantly (P < 0.0001) to 2.418 pg per cell when exposed to 1 nM AuNPs. Regarding immune cell populations in mouse blood directly exposed to 0.1 nM AuNPs, heterogeneity in nanoparticle association varied across immune cell populations. We observed diverse levels of gold association (median, range pg/cell) in NK cells (0.0132, 0.0014-0.0265), dendritic cells (0.0131, 0.0004-0.0272), monocytes (0.0121, 0.0006-0.0272), granulocytes (0.0126, 0.0004-0.0272), B cells (0.0099, 0.0003-0.0274), CD4 T cells (0.0072, 0.0004-0.0226), and CD8 T cells (0.0062, 0.0006-0.1113). However, the single cell analysis revealed a monocyte subpopulation had the greatest association with AuNPs with almost 2 orders of magnitude greater association than NK cell median. These findings highlight the heterogeneous association of AuNPs with immune cell subsets in blood. This observation suggests that monocytes and dendritic cells display a higher propensity for interacting with and internalizing the nanoparticles, potentially due to specific receptor-mediated interactions and internalization mechanisms.

Highly efficient non-doped polymer light-emitting diodes (PLEDs) are under great challenge due to inherently structural disorder and unsatisfied carrier transporting capability of conventional linear polymeric emitters in aggregated state, severely hampering their application in cost-effective large-area display equipment and flexible wearable electronics. Herein, we propose the first case of thermally activated delayed fluorescence (TADF) dendronized π-conjugated polymers (DCPs) that involve embedding TADF moiety into π-conjugated backbones and grafting bulk dendritic substituent group onto sidechain. Due to the steric shielding effect of peripheral dendrons on TADF emission core, the inherent exciton aggregation-induced concentration quenching of chromophores can be effectively mitigated, and thus maintaining superior photoluminescence quantum yields of over 80% in neat films. Furthermore, the carrier motilities of second-generation TADF DCP emitter, PDB3Cz, can reach 1.02 × 10-2 cm2 V-1 s-1 together with preponderant horizontal dipole ratios of 80%, which are derived from the vertically aligned conjugated backbones of TADF DCPs and extendedly paralleled pendant TADF moieties to the substrate, respectively. As a result, the solution-processed non-doped PLEDs based on PDB3Cz achieve state-of-the-art device performances with attractive maximum external quantum efficiency of 27.5%, which is the highest values among non-doped TADF PLEDs.

Salt-sensitivity of blood pressure (SSBP) is a significant cardiovascular risk factor, but its underlying immunometabolic mechanisms remain unclear. Chemerin, an adipose-derived inflammatory mediator linked to vascular dysfunction, was studied in 30 hypertensive adults (mean age 53.1 years; 53% female; mean BMI 32.1 kg/m2) during an inpatient salt-sensitivity protocol. Participants underwent salt-loading and salt-depletion phases over three days. Plasma and urine chemerin levels were measured, alongside immune cell phenotyping and transcriptomic profiling using CITE-seq, RNA-seq, and NanoString. Plasma chemerin increased significantly from salt-loading to salt-depletion (100.4 to 125.8 pg/mL; p = 0.008) and was higher in salt-sensitive individuals during depletion (141.2 vs. 108.6 pg/mL; p = 0.02). Plasma chemerin correlated with systolic blood pressure (SBP) during salt depletion (R2 = 0.20, p = 0.01), while urinary chemerin increased but did not correlate with SBP. In vitro, high-sodium media suppressed CMKLR1 (chemerin receptor) expression in monocytes (p < 0.01). CITE-seq revealed a 1.8-fold enrichment of CMKLR1 in classical monocytes in salt-resistant individuals compared to salt-sensitive ones, with CMKLR1 inversely correlating with ΔSBP (R2 = 0.47, p = 0.03) and ΔMAP (R2 = 0.72, p = 0.004). CMKLR1 was linked to glycolytic and oxidative phosphorylation gene upregulation, and its expression in dendritic cells correlated with urinary lactate and fumarate levels. The chemerin-CMKLR1 axis is dysregulated in SSBP, influencing monocyte and dendritic cell metabolism and blood pressure. Chemerin and CMKLR1 may serve as biomarkers and therapeutic targets for salt-sensitive hypertension.

Hepatocellular carcinoma (HCC) exhibits a suboptimal response to immune checkpoint blockade (ICB) therapy; to overcome this resistance, we aimed to delineate key immune resistance factors via multi-omics analysis, develop strategies to block their immunosuppressive axes, and engineer a targeted nanosystem to enhance immunotherapy efficacy against PD-1 resistance in HCC. Using transcriptomic and proteomic data from anti-PD-1-treated HCC patients, along with functional validation in murine models and mechanistic molecular and cell biology studies, we identified transketolase-like 1 (TKTL1) as a dual-nature biomarker where overexpression predicted poor baseline prognosis yet enhanced response to ICB. Mechanistically, TKTL1 diverts glucose flux into glycolysis rather than pentose phosphate pathway (PPP), recruiting USP9X to deubiquitinate and stabilize HIF-1α, which upregulates HK2 to amplify glycolytic output and lactate accumulation. This metabolic rewiring orchestrates dual immunosuppressive circuits through HIF-1α-driven CCL4 secretion recruiting PD-L1high dendritic cells (DCs), coupled with lactate-induced TRIM28K408 lactylation that stabilizes PD-L1 by blocking ubiquitin-mediated degradation. We engineered a hepatoma-membrane-coated MnO₂ nanosystem (CQLH) co-delivering a TKTL1 inhibitor and lactate oxidase, which disrupted the TKTL1-HIF-1α-HK2 axis, depleted lactate, and reprogrammed the tumor microenvironment, thereby enhanced anti-PD-1 therapy to suppress tumor growth, especially in TKTL1high tumors. These findings define a critical "TKTL1-glycolysis-lactate-DC" axis driving anti-PD-1 sensitivity in HCC, position TKTL1 as both a potential biomarker for ICB response and a tractable therapeutic target, and demonstrate that the targeted CQLH nanosystem overcomes resistance and enhances anti-PD-1 efficacy, offering a precision immunotherapeutic strategy for TKTL1high HCC.

Objective: To explore the predictive value of combined prediction model for pathological upgrading to endometrial carcinoma (EC) after hysterectomy in patients with endometrial hyperplasia (EH). Methods: A total of 109 EH patients who underwent hysterectomy in Tianjin Medical University General Hospital from March 2017 to January 2023 were retrospectively enrolled. According to the postoperative pathological results, they were divided into EC group (63 cases) and EH group (46 cases). The clinical data, hysteroscopic manifestations, ultrasound, pelvic magnetic resonance imaging (MRI) and tumor markers were collected. Binary logistic regression was used to analyze the independent risk factors and establish a combined prediction model, which was internally validated by Bootstrap repeated sampling method to evaluate the discrimination and calibration of the combined prediction model (hysteroscopy performance, ultrasound, MRI, tumor markers). The receiver operating characteristic curve and decision curve were drawn to analyze the predictive efficacy and net clinical benefit. Results: (1) Univariate analysis showed that compared with the EH group, the EC group had a higher proportion of diabetes mellitus, a younger age at menarche, a longer duration of irregular menstruation, and a higher proportion of nulliparous and non-pregnant patients (all P<0.05). Under hysteroscopy, the proportion of endometrial polypoid change, irregular polypoid change, tumor necrosis and rupture, brain circuit or dendritic growth and hysteroscopy score in EC group were significantly higher than those in EH group (all P<0.05). Imaging examination showed that the endometrial thickness, detection rate of the mass, the proportion of enhanced endometrial echo, the abundance of endometrial blood flow, the proportion of unclear boundary between the endometrium and the muscle layer, the proportion of increased diffusion-weighted imaging (DWI) signal of the endometrium or the mass, and the proportion of interrupted combined zone in the EC group were higher than those in the EH group (all P<0.05). The results of tumor marker detection showed that the serum human epididymis protein 4 (HE4) level in EC group was significantly higher than that in EH group (P=0.005). (2) Multivariate analysis showed that diabetes mellitus (OR=4.884), enhanced intimal echo under ultrasound (OR=11.234), heterogeneous high signal on DWI (OR=7.031), and elevated serum HE4 level (OR=1.032) were independent risk factors for postoperative pathological upgrading of EH patients to EC (all P<0.05). (3) The combined prediction model was established by combining the above indicators, and the area under the corrected curve was 0.811 (95%CI: 0.720-0.902). The sensitivity of the combined prediction model in predicting postoperative pathological upgrade to EC in patients with EH was higher than that of hysteroscopy score (82.1% vs 44.6%), and the specificity was lower than that of hysteroscopy score (71.0% vs 96.8%). Conclusion: The combined prediction model has a high predictive sensitivity, which provides a reference for predicting the postoperative pathological upgrade of EH patients who plan to undergo total hysterectomy, helps to reduce the risk of missed diagnosis of EC, and is expected to become a supplementary tool for preoperative risk assessment of EH patients who plan to undergo total hysterectomy.

Hepatocellular carcinoma (HCC) arises from chronic inflammation and immune tolerance, posing substantial challenges for immunotherapy. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling is a central immunological hub linking innate immune sensing to adaptive immune responses in tumors. In HCC, cGAS-STING signaling exhibits a context-dependent dual role across multiple hepatic cell types, including hepatocytes, hepatic stellate cells and immune cells, orchestrating both anti-tumor immunity and pro-tumorigenic inflammation. While acute activation enhances dendritic cell maturation, antigen presentation, and CD8+ T-cell priming to boost anti-tumor immunity, sustained or dysregulated cGAS-STING signaling promotes chronic inflammation and subsequently remodels an immunosuppressive tumor microenvironment (TME) to promote tumorigenesis. This dual functionality positions the cGAS-STING signaling as both a therapeutic opportunity and a critical constraint in HCC immunotherapy. Recent advances highlight the translational potential of STING-targeted strategies, including synthetic agonists, combination regimens with targeted therapies, immune checkpoint inhibitors (ICIs) as well as nanomaterial-based delivery systems. At the same time, clinical translation remains constrained by systemic inflammatory toxicity, context-dependent tumor-promoting inflammation, pathway refractoriness or silencing, and the lack of validated biomarkers for patient selection. In this review, we summarize the molecular mechanisms, cell-type-specific functions and intercellular crosstalk of cGAS-STING signaling in HCC, and discuss therapeutic strategies and translational challenges. We propose future directions focusing on spatiotemporal activation, precision delivery, and biomarker-guided interventions to exploit the therapeutic potential of targeting the cGAS-STING signaling in HCC.

Adoptive cell therapy (ACT) remains challenging in solid tumors, where poor tumor infiltration, metabolic heterogeneity, and an immunosuppressive tumor microenvironment (TME) constrain therapeutic efficacy. Here, we developed magnetically and metabolically programmed macrophage-based immune microrobots (immunobots) for active solid tumor immunotherapy. The immunobots are constructed by loading bone marrow-derived macrophages (BMDMs) with lipopolysaccharide (LPS)-modified Janus L10-FePt magnetic microrollers (LMRs), which function both as an external magnetic actuation unit and as biochemical regulators that program macrophages into an anti-tumor phenotype. Optimized LMR loading endows the immunobots with robust propulsion, retention under flow, and enhanced barrier penetration. LMRs drive M1-like polarization through LPS-induced inflammatory activation and FePt-derived labile iron-amplified oxidative stress, leading to altered iron homeostasis, elevated reactive oxygen species (ROS), and enhanced NF-κB signaling. Functionally, immunobots induce ferroptosis-associated immunogenic cell death (ICD) in tumor cells. In vivo, magnetically guided immunobots suppress tumor growth through coordinated remodeling of the tumor immune landscape, including tumor-associated macrophage (TAM) reprogramming, dendritic cell maturation, and enhanced CD8+ T cell activation. Collectively, this work establishes a magnetically guided and metabolically programmed microrobotic immunotherapy strategy for overcoming the physical, metabolic, and immunological barriers that limit cellular therapy in solid tumors.

Sodium (Na) metal anodes are attracting great attention as next-generation energy storage systems due to their high theoretical capacity, abundant resources, and low cost. However, an unstable solid-electrolyte interphase (SEI), uncontrolled dendrite growth, and large volume changes are major factors limiting the practical application of Na metal anodes. Herein, we develop a Na-Sb alloy anode featuring a three-dimensional sodiophilic Na3Sb framework embedded within a metallic Na matrix. The interconnected Na3Sb framework homogenizes the Na+ flux and provides abundant Na nucleation sites, enabling uniform Na deposition while effectively suppressing dendrite growth. Moreover, the engineered interface promotes the formation of a dense, NaF-rich inorganic SEI with high mechanical strength and chemical stability, which effectively accommodates volume changes and stabilizes the Na metal/electrolyte interface during repeated cycling. Consequently, the NSF-3||NSF-3 symmetric cell delivers remarkably stable cycling for over 1000 h at 0.5 mA cm-2 with a capacity of 0.5 mAh cm-2, exhibiting significantly improved interfacial stability and Na plating behavior. This work demonstrates that constructing a sodiophilic Na3Sb framework is an effective strategy for regulating Na deposition and stabilizing the Na metal interface, providing a practical pathway toward high-energy-density and long-life sodium metal batteries.

Microwave ablation (MWA) for large hepatocellular carcinoma (HCC) is frequently compromised by non-uniform thermal distribution and immunosuppressive niche formation. To address these challenges, we engineered an injectable bimodal nanodepot (TCPD) via catalytic crosslinking of dopamine-modified hyaluronic acid by microwave thermal converter cesium-doped Prussian blue, enabling co-delivery of glutaminase 1 inhibitor Telaglenastat and sonosensitizer Chlorin e6. Under combined MWA and ultrasound irradiation, TCPD nanodepot disrupts cellular antioxidant defenses and bioenergetic pathways through glutaminolysis-TCA cycle blockade, metabolically sensitizing large tumors to spatially complementary sono-thermal ablation and enabling complete treatment coverage. This multimodal intervention induces multiple subcellular stresses, including mitochondrial and endoplasmic reticulum dysfunction, genotoxicity, and NAD+ depletion, which converge to facilitate PANoptosome assembly and immunogenic PANoptosis while activating the cGAS-STING pathway. Subsequent release of damage-associated molecular patterns and immunoregulatory cytokines promotes dendritic cell maturation, M1 macrophage polarization, and T lymphocyte infiltration, ultimately reprogramming the immunosuppressive microenvironment toward an immune‑activated niche. Integration with anti-PD-1 therapy further reinvigorates cytotoxic T lymphocytes and establishes antitumor immune memory to suppress tumor progression and metastasis, offering a multimodal therapeutic strategy for large HCC.

The existing designs of buffer for all-solid-state Li-metal batteries (ASSLMBs) are mostly limited to static optimization of single functions and lack systematic regulation of the dynamic competition among ionic conduction, electron distribution, and interfacial lithiophilicity. Herein, a conduction-nucleation competition mechanism is proposed firstly, clarifying that lithium deposition is governed by the synergy of these three factors. Guided by this principle, a self-adaptive gradient buffer layer composed of soft carbon and Mg3N2 (SCMN) is designed. After lithiation, the buffer forms a continuous lithiophobic/lithiophilic gradient and subsequently undergoes in-situ conversion into highly ion-conductive Li3N and highly electron-conductive/ lithiophilic Li-C/Li-Mg alloys during electrochemical activation, enabling dynamic interface self-optimization. The gradient structure creates a fast ion-electron dual conduction network, guiding bottom-top lithium deposition within the buffer layer without volume expansion. Consequently, the symmetric cells achieve stable cycling over 1600 h at 1.5 mA cm- 2 and remain stable even under low stack pressure (15 MPa). The LiCoO2-based full cells deliver ultra-stable cycle with 98.5% capacity retention after 200 cycles at 0.1 C. Additionally, the full cells paired with high-voltage LiNi0.8Co0.1Mn0.1O2 cathodes exhibit exceptional cycling stability at high loading (4.45 mg cm-2). This work demonstrates a mechanism-driven design paradigm toward high-energy, long-life ASSLMBs.