Peroxynitrite (ONOO⁻) is central to both physiological signaling and diverse pathological processes. Its dual nature underscores the need for precise tools to investigate its spatiotemporal dynamics and biological functions. However, the controlled generation and real-time tracking of ONOO⁻ remain challenging due to its short half-life and high reactivity. Current small-molecule ONOO⁻ donors often suffer from limitations such as slow release, low efficiency, and off-target effects. To overcome these challenges, here we report a new class of photo-triggered ONOO⁻ donors (O-PND and Si-PND) based on a single rhodamine-derived scaffold, enabling precise ONOO⁻ release with built-in fluorescence calibration. These molecular tools facilitate efficient ONOO⁻ generation under blue light irradiation, as confirmed in PBS and live cells, and exhibit excellent cell membrane permeability. Upon intracellular activation, O-PND and Si-PND induced a marked increase in oxidative stress. However, further studies reveal that the rapid transient ONOO⁻ burst in RAW264.7 cells was insufficient to significantly modulate macrophage polarization. Collectively, these robust self-reporting ONOO⁻ donors provide a powerful single-molecule platform for investigating ONOO⁻-mediated biological mechanisms with spatiotemporal precision.

The clinical application of tumor vaccines is hindered by challenges such as time-consuming and costly production processes. In this context, in situ cancer vaccines represent a promising strategy by leveraging endogenous tumor antigens to elicit robust antitumor T cell responses. Herein, a photoactivatable tumor-targeting in situ nanovaccine, Lipo-D8-6, was constructed using cRGD-functionalized liposomes that co-encapsulated the photosensitizer chlorin e6 and a cleavable immunoadjuvant conjugate D8, allowing light-triggered synchronous activation of three therapeutic modules. Upon near-infrared light irradiation, Lipo-D8-6 generates reactive oxygen species that exert direct cytotoxicity on tumor cells and induce immunogenic cell death, while concurrently cleaving the responsive linker within D8 to achieve the controlled release of R848. In vivo biodistribution analysis confirmed the superior intratumoral accumulation of Lipo-D8-6, facilitating precise treatment. In a large-volume tumor model, the nanovaccine exhibited pronounced antitumor efficacy, accompanied by enhanced tumor infiltration of CD8⁺ T cells. Overall, this work provides a simplified and effective approach for developing in situ nanovaccines that enable synergistic photodynamic immunotherapy with precise spatiotemporal control over immune activation.

Lipid peroxidation (LPO) in foam cells is crucial for regulating atherosclerosis progression. It correlates with lipid uptake and the state of lipid droplets. In this study, we report a lipid droplet-targeted fluorescent LPO probe, Ld-LPO. It selectively responds to LPO, resulting in a significant fluorescence shift from 590 to 525 nm, enabling a ratiometric imaging of LPO in lipid droplets. Ld-LPO traces lipid droplets in foam cells, revealing a correlation between LPO and lysosomal engulfment. We found that lipid droplets engulfed by lysosomes exhibit higher LPO, attributed to low-density lipoprotein accumulation in lysosomes. Furthermore, Ld-LPO is compatible with dual-color flow cytometry, facilitating high-throughput analysis of LPO in foam cells.

This study constructed an in vitro blood-brain barrier (BBB) transwell model to investigate the regulatory effects and mechanisms of the photothermal effects of gold nanorods (AuNRs) excited by the second near-infrared region (NIR-II) on BBB permeability. The experimental results showed that the photothermal effects of NIR-II + AuNRs significantly decreased trans-epithelial electrical resistance (TEER) and increased the permeability of fluorescein isothiocyanate (FITC)-dextran, indicating that it can effectively open the BBB. This effect was reversible, and the TEER and FITC permeability returned to baseline levels within 24 h after treatment. Mechanistic studies revealed that BBB opening did not rely on apoptosis, cytoskeletal disruption, mitochondrial dysfunction, or inflammation. The opening of the BBB was closely associated with a temporary decrease in the expression and conformational change of the tight junction protein occludin due to the photothermal effect. Molecular simulations and docking analysis revealed that the heat shock protein HSP70 could bind to the conformationally altered occludin, supporting the regulatory role of photothermal effects on tight junction proteins. In summary, NIR-II + AuNRs achieved safe and reversible opening of the BBB by regulating the conformation and expression of tight junction proteins, providing a deeper insight for further research on BBB and the treatment of neurological diseases.

Supramolecular materials, characterized by dynamic reversibility and responsiveness to environmental stimuli, have found widespread applications in numerous fields. Unlike traditional materials, supramolecular materials that rely on non-covalent interactions can allow spontaneous reorganization and self-healing at room temperature. However, these materials typically exhibit low strength due to the weak bonding energies of non-covalent interactions. This study presents the development of a high-strength self-healing supramolecular material that combines multiple interactions including ionic bonding, hydrogen bonding, and coordination bonding. The material, formed by the aggregation of the negatively charged picolinate-grafted copolymer (PCM) with positively charged hyperbranched molecules (HP), is further enhanced by Eu³⁺ ion complexation. The resulting film exhibits a high modulus of 427 MPa, tensile strength of 10.5 MPa, and toughness of 14.7 MJ m⁻³. Meanwhile, the non-covalent interaction of this supramolecular material endows it with a self-healing efficiency of 92% within 24 h at room temperature, as well as multiple remolding properties. The incorporation of lanthanide ions also imparts tunable fluorescence. This study not only provides insights into the development of high-strength self-healing materials but also offers new possibilities for the functionalization of supramolecular materials.

Cutaneous squamous cell carcinoma (cSCC), the second most common skin cancer, requires early and accurate detection to optimize clinical management. Fluorescence imaging has emerged as a non-invasive and cost-effective tool with high sensitivity for tumor diagnosis; however, existing probes for cSCC are limited in achieving rapid and specific imaging. In this study, we introduce FC-1, a dual-tandem activatable fluorescent probe designed for precise cSCC diagnosis by simultaneously targeting fibroblast activation protein α and cathepsin C (CTSC). This dual-locked activation strategy effectively reduces nonspecific signals in normal tissues while enhancing diagnostic specificity. In vivo studies in SCC-7 xenografted mice demonstrated FC-1's ability to visualize subcutaneous tumors with high sensitivity and specificity. Moreover, FC-1 enabled clear differentiation between cSCC and keloids. The probe's dual-activation mechanism and robust performance underscore its potential as a clinically translatable tool for early cSCC detection and differential diagnosis.

The development of electronic circuits designed to emulate the functionality of biological neural networks has increased significantly in recent years. Specifically, memristor-based neuromorphic operation has been demonstrated using various material combinations. One class of devices replicates the ion-concentration-gradient buildup that precedes neurotransmitter release in biological synapses. Some of these devices incorporate amino-acid-rich solutions as an active layer. This work presents a density functional theory study of such a device. The interaction between an Ag-filamentary memristor and different Hydrogen concentrations in a tyrosine-rich environment was evaluated. Two mutually exclusive structures were studied, and the resulting source-to-drain currents were compared with experimental observations. One structure was based on Tyrosine-H blocks linked to Ag atoms as a charge conduction path, while the other placed these blocks in parallel with Ag partial filaments between the source and drain. The results indicate that the second aligns with experiments and supports the hypothesis that tyrosine can act as an enabler for proton-mediated charge transport. Furthermore, the insights into the electronic transport properties of specific molecules can provide a theoretical background for designing advanced Hydrogen sensors and amino acid detectors.

With increasing drug resistance, Candida infections have posed serious threats to public health. Photodynamic therapy harnesses light to destroy pathomycete, providing a smart strategy for combating of Candida infections. However, due to lack of organelle targeting ability and bad extracellular polymeric substances penetrability, current photosensitizers (PSs) are far from desirable to clean biofilms and fight against drug resistance. Herein, a mitochondrion targeting aggregation-induced emission PS, LIQ-TPA-TZ, was developed for the efficient photodynamic treatment of oral Candida infection. LIQ-TPA-TZ has good singlet oxygen and hydroxyl radical generation ability, which can efficiently kill the Candida guilliermondii (C. guilliermondii) and eradicate the biofilm. It not only causes mitochondrial damage by disruption of mitochondrial respiratory chain and oxidative stress-related gene but also inhibits fungal adhesion and filamentous growth to prevent Candida colonization, mycelia growth and biofilm formation, which is favorable for eliminating the potential drug resistance. In the mouse oropharyngeal Candida biofilm infection model, LIQ-TPA-TZ significantly eliminates infection, alleviates inflammation, and accelerates mucosal defect healing. This study provides a favorable strategy for confronting drug resistance, which may be a potential Candidate for the treatment of Candida infection.

Circularly polarized luminescence (CPL)-active materials have a wide range of technological applications. Traditionally, creating CPL-active materials relies on the use of chiral luminophores. In contrast, supramolecular assembly introduces an innovative and promising strategy for developing CPL-active materials not only from chiral luminophores but also from achiral species. This approach significantly enriches the diversity of CPL-active materials. It also offers an effective means to optimize the performance of CPL-active materials, such as enhancing the asymmetry factor |g_lum|. Compared to polymers, the assembly of small molecules is generally easier to control. This review systematically summarizes the recent progress and developments in CPL from small-molecule assemblies, particularly focusing on differences, merits, and demerits of three typical assembly modes. The aim is to provide valuable insights for the future development of chiroptical materials.

Microneedles (MNs) offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin, leveraging the abundance of tissue-resident immune cells to elicit robust and durable immune responses. Compared to traditional intramuscular or subcutaneous vaccination methods, MN-based vaccines demonstrate superior patient compliance, enhanced antigen stability, and heightened immunogenicity, positioning them as a promising tool in biomedical applications. This review provides a comprehensive overview of the materials and fabrication techniques used in MN preparation, explores their structural classifications, and examines the role of antigens and adjuvants in optimizing vaccine efficacy. Furthermore, the diverse applications of MN delivery systems in preventing infectious diseases, advancing tumor immunotherapy, and addressing other immune-related conditions are discussed.

Curcumin, a bioactive compound extracted from Curcuma longa. L., demonstrates significant therapeutic potential in inflammatory diseases. This study aims to explore the effects of curcumin on hyperuricemia with acute gout and associated renal dysfunction in a mouse model. The results show that curcumin treatment alleviates ankle joint swelling, reduces inflammatory cytokines IL-1β and TNF-α, and lowers serum uric acid concentrations. High-dose curcumin notably inhibits xanthine oxidase (XOD) activity, a key enzyme in uric acid production, while it enhances the renal expression of the urate transporter ABCG2, thereby promoting uric acid excretion. Furthermore, curcumin effectively mitigates renal injury as evidenced by reduced serum creatinineand blood urea nitrogen levels and suppresses renal inflammation. At the molecular level, curcumin exerts potent antioxidant effects by lowering reactive oxygen species (ROS) levels in both cultured HK-2 human renal tubular epithelial cells and RAW264.7 mouse macrophages. The curcumin-mediated effects are associated with the disruption of NEK7-NLRP3 complex formation, leading to the suppression of the ROS/NEK7-NLRP3 inflammasome pathway. This, in turn, inhibits pyroptosis and the subsequent release of mature IL-1β. These findings suggest that curcumin not only reduces uric acid production but also modulates inflammation through ROS-scavenging properties and its ability to inhibit the NLRP3 inflammasome.

Developing metal-free, purely organic photocatalysts with high recyclability and the ability to utilize red light to yield specific reactive oxygen species for aerobic photocatalysis is both crucial and challenging in current research. Herein, we first found that a type-I photosensitizer, EtNBS-H, can achieve red-light-driven aerobic photocatalysis with remarkable catalytic performance and facile recoverability. Upon irradiation with red light, EtNBS-H exclusively generates O₂^−•, enabling the efficient hydroxylation of arylboronic acids, and oxidization of thioethers and other substrates with conversion exceeding 99%. Significantly, EtNBS-H stands out for its simple recovery and reuse through a facile pH-tunable acid-base reaction. This allows for the attainment of high-purity products through extraction, and enables the retrieval of the photocatalyst from the reaction medium for subsequent reuse with an average recovery rate exceeding 94%. Moreover, utilizing EtNBS-H as a photocatalyst in the scale-up reaction, the gram-scale products with a yield of >95% and purity of >99% were obtained, highlighting its potential for the guidance of developing recyclable organic photocatalysts that harness red light. This work offers a promising approach for sustainable and large-scale photocatalytic organic synthesis.