Developing organic type I photosensitizers (PSs) that generate less oxygen-dependent reactive oxygen species (ROS) has long been recognized to be an appealing yet significantly challenging task in the field of photodynamic therapy (PDT), owing to the high oxygen dependency of conventional PDT, which impairs its overall therapeutic efficacy, particularly in hypoxic solid tumors. Herein, a molecular fluorination strategy to finely regulate PSs with bright near-infrared (NIR) fluorescence and superior type I ROS generation ability was exploited. Benefited from the improved donor-acceptor interaction, promoted intersystem crossing process, and increased spin-orbit coupling (SOC) constant, the optimal TIBT-5F simultaneously exhibits broad absorption with a larger molar extinction coefficient in the visible-light region, bright NIR fluorescence emission and stronger type I ROS generation efficiency, making TIBT-5F a promising candidate for precise NIR fluorescence-guided PDT. The as-prepared TIBT-5F nanoparticles (NPs) can quickly accumulate in the tumor site, effectively produce both type II and type I ROS and prominently suppress the tumor growth under a safe white light irradiation (40 mW/cm2) with minimized systemic toxicity. This study thus offers a new insight into constructing advanced type I PSs for precise fluorescence imaging-guided tumor theranostics.

Pyroptosis is a highly immunogenic form of programmed cell death with great potential for cancer immunotherapy. However, achieving tumor-selective and intrinsically controllable induction of pyroptosis remains challenging. Here, we report a nanoparticle-based mitochondrial disruptor, termed nanoMd/PA, which acts as an intrinsic pyroptosis inducer by directly destabilizing mitochondrial membranes in tumor cells. Inspired by the membranolytic activity of antimicrobial peptides, nanoMd/PA is engineered with a guanidinium-rich shell that selectively accumulates in tumor mitochondria and disrupts membrane integrity through a pore-forming mechanism, thereby initiating gasdermin-mediated pyroptosis. The nanoparticle is further shielded with a pH-responsive polymer layer that remains inert during circulation but activates its mitochondrial-lytic function specifically within the acidic tumor microenvironment. In an orthotopic colorectal cancer model, nanoMd/PA treatment triggers robust pyroptosis, resulting in significant tumor suppression, extended survival, and potent inhibition of metastatic spread, all without detectable systemic toxicity. This work establishes a carrier-independent, nanomaterial-driven approach to induce pyroptosis through direct mitochondrial membrane disruption, offering a new paradigm for activating antitumor immunity with synthetic, intrinsically immunomodulatory nanoparticles.

Pyroelectric catalysis has shown promising prospects for sustainable energy generation and medical treatments. However, its potential is limited by intrinsically low pyroelectric coefficients and insufficient interfacial reactivity, resulting in poor reactive oxygen species (ROS) output. In this study, we design Ba(Ti0.85Zr0.15)O3 (BTZ) nanocatalysts, featuring enhanced polarization tunability and oxygen-vacancy-rich interfaces, for efficient NIR-II-driven photo-pyroelectric cancer therapy. Molecular dynamics and phase-field simulations indicate that Zr incorporation maintains strong polarization while facilitating rapid polarization switching via multiscale nanodomain formation. This results in an ultrahigh pyroelectric coefficient (3505 µC m-2 K-1), representing a 678% enhancement over pristine BaTiO3. Interface engineering introduces oxygen vacancies that enhance NIR-II photothermal conversion and serve as reactive sites to facilitate the dissociation of water molecules. Density functional theory calculations reveal that Zr doping narrows the bandgap and redistributes conduction band electrons, while interfacial oxygen vacancies facilitate water adsorption through optimized hydroxyl binding. As a result, synergistic pyrocatalysis and peroxidase-like activity under NIR-II-driven mild thermal cycling enable robust multipath ROS generation. Both in vitro and in vivo studies confirm efficient tumor cell ablation via NIR-II induced pyroelectric therapy. This work presents a co-engineering strategy integrating polarization and interface design to overcome long-standing limitations in pyroelectric catalysis, advancing its application in precision oncology.

Wound exudate contains rich biochemical markers, among which dynamic pH fluctuations serve as a key predictor of infection progression and healing prognosis. However, real-time pH monitoring remains limited by the lack of platforms enabling exudate extraction and stable sensing. Here, we present an asymmetric theranostic Janus wound dressing that integrates unidirectional exudate transport, wide-gamut colorimetric pH sensing, and antibacterial therapy into a single closed-loop platform. The bilayer rapidly drains exudate from the curcumin/Ag-loaded hydrophobic polyurethane (PU) layer into a hydrophilic hydrogel for biochemical analysis. To overcome the inherent instability and leaching issues of conventional pH indicators, phenol red is confined within zeolitic imidazolate framework-8 nanoparticles, forming a leaching-resistant optical sensor with enhanced sensitivity and a broadened dynamic color range. This strategy enables accurate, lighting-independent pH quantification via a deep-learning-assisted smartphone application, enabling objective in situ assessment of infection risk and healing status. Both in vitro and in vivo evaluations confirm that this platform not only suppresses infection and accelerates wound closure but also provides prognostic biochemical feedback with clinical relevance. This work presents a comprehensive AI-assisted theranostic strategy that integrates wound microenvironment engineering with digital health tools to precision wound management.

The recovery of rare earth elements from waste neodymium magnets is of great economic and environmental significance. As the most widely used rare earth permanent magnet material, neodymium magnets contain a substantial amount of iron (approximately 60-70wt%). The chemical behavior of iron closely resembles that of rare earth elements, making the separation process highly challenging. To address the issue of efficiently separating iron and rare earth elements from neodymium magnets, this paper systematically investigates the extraction and separation behaviors of a representative rare earth element, Pr3+, and Fe3+ using a series of malonamide extractants (MAs) in hydrochloric acid medium. Seven malonamide extractants with different structures were synthesized and characterized. The effects of extractant concentration, temperature, hydrochloric acid concentration, and diluent type on the distribution ratios and separation efficiencies of FeCl3 and PrCl3 were examined in detail. The results demonstrate that by precisely controlling the acidity of the hydrochloric acid solution, this class of extractants can preferentially extract iron while efficiently retaining rare earths in the aqueous phase. Using 0.2mol/L DEDOMA to treat the NdFeB leaching solution resulted in an iron extraction efficiency of 99.70%, whereas the extraction efficiency of the rare earth elements (Nd, Pr, and Dy) was less than 1%. This study provides an important theoretical basis and technical reference for developing novel, efficient, and environmentally friendly rare earth separation systems, particularly for the removal of iron impurities from complex hydrochloric acid leach solutions.

Excessive exudate accumulation and bacterial infection are two major obstacles in the treatment of infected wounds, often leading to prolonged inflammation and significantly delayed healing. Therefore, developing a multifunctional Janus wound dressing that integrates efficient unidirectional moisture drainage with potent antibacterial activity is of urgent clinical importance. Here, we report a multifunctional unidirectional moisture-drainage and bactericidal Janus dressing (MMPC), engineered through a simple surface-modification strategy on commercially available nonwoven fabrics, enabling excellent scalability and translational feasibility. MMPC features an asymmetric architecture comprising a hydrophilic antibacterial layer and a hydrophobic wound-healing-promoting layer. The hydrophilic layer, functionalized with carboxymethyl cellulose gel and methylene blue, exhibits outstanding exudate management and visible-light-driven antimicrobial activity through reactive oxygen species generation. The hydrophobic layer, composed of polyurethane and curcumin and designed to directly interface with infected tissues, facilitates unidirectional exudate removal while promoting cellular proliferation and tissue regeneration. In a murine infected-wound model, MMPC exhibits a comprehensive therapeutic profile under the white LED light irradiation, combining exudate management and sustained drug release with strong antibacterial effects to ultimately achieve a remarkable 93.8% rate of wound closure. Importantly, the use of modified commercial nonwoven substrates ensures low-cost fabrication and strong clinical translation potential, positioning MMPC as a promising next-generation wound dressing for effective management of bacteria-infected wounds.

The heterogeneity of cancer stem cells and the immunosuppressive hypoxic microenvironment are key challenges in the development of therapeutic vaccines for solid tumors. In this study, oxygen was attempted as an adjuvant to investigate the enhancing immunotherapeutic efficacy of cancer nanovaccines. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) that co-modified with anti-CD3 and anti-epidermal growth factor receptor antibodies (2P@Lipo-NBs-O2) was developed enabling T cell-tumor cell bridging. BMS 202, a programmed cell death 1/programmed cell death 1 Ligand 1 (PD-L1) inhibitor, was loaded yielding 2P@Lipo-BMS-NBs-O2, which was found to reduce the expression levels hypoxia-inducible factor-1α and PD-L1, synergistically enhanced the pharmacodynamics of BMS 202, meanwhile, enhanced cytotoxic T-cell infiltration. Combined technology of oxygen delivery and T cell redirection effectively enhances cancer immunotherapy. Further incorporation of a fused cytomembrane (FM) from dendritic and B16F10 cells produced FM-2P@Lipo-BMS-NBs-O2, which exhibited superior heterogeneous tumor growth suppression, reduced stemness gene expression, increased CD8+ T-cell infiltration, and elevated IFN-γ levels in serum. Oxygen-carrying nanovaccine possess the features of oxygen delivery, T cell redirection and FM coating, represents full activation of T-cell function and a potent reduction of tumor stemness, offering a promising strategy for the treatment of highly heterogeneous solid tumors.

The emerging second near-infrared (NIR-II, 1000–2300 nm) fluorescence imaging based on microscopy set-ups (NIR-II FLI MS) has been proven to enable real-time tracking of dynamic physiological processes and facilitate the reconstruction of clear two- and three-dimensional morphological images of living tissues, which can offer high signal-to-background ratio and imaging contrast of live tissues at the cellular level. Focusing on the significant role of NIR-II FLI MS in intravital imaging and bioanalysis, in this contribution, we begin with the performance trade-off between NIE-II fluorescence probes and microscopy set-ups, focused on specific requirements for fluorescent probes across different NIR-II FLI MS modalities and feasible strategies to enhance their optical performances of the different NIR-II probes. Subsequently, we summarize recent advances in NIR-II microscopy set-ups, with an emphasis on the operational principles and specific requirements of wide-field, confocal, and light-sheet systems for high-performance in vivo detection. The cutting-edged applications of these probes and set-ups for in vivo NIR-II FLI MS is also discussed in detail. Finally, we provide a comprehensive and interdisciplinary analysis of the enduring challenges and prospective directions within this field, aiming to inspire further development of novel NIR-II high-performance probes and microscopy technologies for advanced intravital detection and facilitate the transition of in vivo NIR-II FLI MS from “technology-driven” to “science-driven”.

Background:Pulmonary mucinous adenocarcinoma (PMA), a rare type of adenocarcinoma, remains controversial in terms of its associated prognosis. We conducted this study to compare the oncological outcomes of lobectomy and sublobectomy for peripheral small-sized PMA. Methods:This retrospective observational study included all patients with peripheral small-sized (≤2 cm) clinical stage IA1-A2 PMA who underwent lobectomy or sublobectomy (with margin distances ≥2 cm or greater than tumor diameter) between January 2015 and December 2018. Recurrence-free survival (RFS) and overall survival (OS) were compared between the lobectomy and sublobectomy groups with Kaplan-Meier curves and log-rank tests. Results:This study examined 279 patients, with 176 cases in the lobectomy group and 103 cases in the sublobectomy group. Recurrence occurred in 8 patients, and 6 patients died. Before and after propensity score matching (PSM), log-rank tests showed no statistical differences between the lobectomy and sublobectomy groups in terms of 5-year RFS (before PSM: 97.0% vs. 98.9%; after PSM: 94.6% vs. 98.9%) or 5-year OS (before PSM: 96.9% vs. 98.8%; after PSM: 94.8% vs. 98.8%), and the recurrence patterns were also similar between the two groups. The incidence of postoperative complications, such as bronchopleural fistula, hydrothorax requiring redrainage, chylothorax, respiratory failure, and pulmonary embolism, also did not differ between the two groups. Conclusions:For peripheral small-sized PMA, sublobectomy yielded an RFS and OS comparable to those of lobectomy.

Despite the tremendous therapeutic promise of activating stimulators of interferon genes (STING) enable to prime robust de novo T-cell responses, biomechanics-mediated immune inhibitory pathways hinder the cytotoxicity of T cells against tumor cells. Blocking cancer cell biomechanics-mediated evasion provides a feasible strategy for augmenting STING activation-mediated anti-tumor therapeutic efficacy. Here, we fabricate a redox-responsive Methyl-β-cyclodextrin (MeβCD)-based supramolecular polyrotaxanes (MSPs), where the amphiphilic diselenide-bridged axle polymer loads MeβCD by the host-guest interaction and end-caping with two near-infrared (NIR) fluorescence probes IR783. The MSPs self-assemble with STING agonists diABZIs into nanoparticles (RDPNs@diABZIs), which enable simultaneous release of MeβCD and diABZIs in the redox tumor microenvironment. After the released diABZIs activate STING on antigen-presenting cells (APCs), de novo T-cell responses are initiated. Meanwhile, the released MeβCD depletes membrane cholesterol to overcome cancer-cell mechanical softness, which enhances the CTL-mediated killing of cancer cells. In the female tumor-bearing mouse model, we demonstrate that RDPNs@diABZIs lead to effective tumor regression and generate long-term immunological memory. Furthermore, RDPNs@diABZIs can achieve significant tumor eradication, with these mice remaining survival for at least 2 months. Activation of stimulator of interferon genes is promising for initiating robust de novo T-cell responses, but biomechanics-mediated immune inhibitory pathways hinder the cytotoxicity of T cells against tumor cells. Here, the authors report redox-responsive supramolecular polyrotaxanes nanoformulations that augment anti-tumor T-cell killing by overcoming cancer-cell mechanical softness.

Antibiofilm treatment, particularly drug-containing wound healing dressings, does not typically penetrate the robust protective extracellular polymeric substance of biofilm and eradicate the bacteria. Here, a rational design of nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6)-based injectable hydrogel, is reported in which the NO release can be triggered by a photothermal effect owing to semiconducting perylene diimide (PDI) J-aggregation fibers. The synthetic PDI derivatives self-assembling into 0D nanoparticles and then aggregating to 1D J fiber is accompanied by absorbance red-shifting from 700 to 790 nm and then to 852 nm. After encapsulating BNN6, a "sandwich roll" (SR) like structure is evenly crosslinked into an injectable hydrogel (SRH) exhibiting a high photothermal convenience efficiency of 72%, which enables the SRH to achieve highly efficient photocontrol NO release. The SRH shows excellent injectability, shape adaptability, and effective antibacterial efficacy over 99% to the E.coli and S. aureus. and remarkable in vivo antibiofilm efficiency of 99.58% by laser irradiation. Furthermore, the synergistic treatment displays the ability to eliminate inflammation, facilitate angiogenesis, and promote collagen deposition, thereby significantly stimulating the healing process of wounds. The semiconducting J-aggregation injectable hydrogel can be a versatile strategy for the treatment of biofilm.

Importance:Image-guided thermal ablation has been administered for patients with T1N0M0 papillary thyroid carcinoma (PTC) who elect to not undergo surgery or receive active surveillance. Considering the indolent nature of PTC, long-term outcomes of ablation are needed. Objective:To investigate l0-year outcomes of thermal ablation in treating T1N0M0 PTC. Design, Setting, and Participants:This multicenter study was conducted at 4 university-affiliated hospitals in China and included 179 consecutive patients with T1N0M0 PTC (median [IQR] volume, 88.0 [163.2] mm3) who underwent thermal ablation between June 2010 and March 2014. Patients who were ineligible to undergo surgery or elected not to were included, and patients had PTC tumors that were smaller than 20 mm as confirmed by biopsy; no clinical or imaging evidence of extrathyroidal extension, lymph node metastasis (LNM), or distant metastasis; and no history of neck irradiation. Main Outcomes and Measures:The primary outcomes were disease progression (LNM, newly developed tumors, persistent tumors, and distant metastasis) and disease-free survival (DFS). Secondary outcomes were technical success, volume reduction rate, tumor disappearance, complications, and delayed surgery. DFS was calculated using a Kaplan-Meier analysis. Results:Among the 179 patients, the mean (SD) age was 45.8 (12.7) years, and 118 (65.9%) were female. During a mean (SD) follow-up period of 120.8 (10.8) months, disease progression was found in 11 of 179 patients (6.1%), including LNM in 4 patients (2.2%), newly developed tumors in 6 patients (3.3%), and persistent tumor in 1 patient (0.6%). The 10-year DFS was 93.9%. The technical success, median volume reduction rate, and tumor disappearance rate was 100%, 100%, and 97.2%, respectively. The magnitude of the disease progression (6.1% vs 7.1%; difference, 1.0%; 95% CI, -6.5% to 25.6%) and DFS (93.9% vs 92.9%; difference, 1.0%, 95% CI, -6.5% to 25.6%) between patients with T1a and T1b tumors was small. The difference in the rate of tumor disappearance between T1a and T1b tumors was large (99.4% vs 71.4%; difference, 28.0%; 95% CI, 10.9%-54.0%). One patient experienced transient voice hoarseness (0.6%). Because of anxiety, 1 patient underwent delayed surgery (0.6%). Conclusions and Relevance:The results of this 10-year multicenter cohort study suggest that thermal ablation is an effective and safe alternative for patients with T1N0M0 PTC who do not undergo surgery or receive active surveillance. For safe and effective treatment, accurate radiologic evaluation, an understanding of ablation techniques, and experienced physicians are recommended.

We report the rational design and biological validation of ZnMA, a multifunctional nanovaccine engineered through integration of zinc-doped carbon dots (ZnCDs), TLR4-targeting mannan polysaccharide, and tumor-specific antigens. Mannan functionalization through esterification chemistry yields ZnM with optimized biodistribution and lysosomal escape capability. Antigen-loaded ZnMA exhibits multifunctional immunotherapeutic effects by promoting dendritic cell maturation and inducing Th1-polarized cytokine production. Synergistic CD8+ T cell expansion and Treg/MDSC depletion by ZnMA induced near-complete tumor regression, effectively rebalancing the tumor microenvironment toward antitumor immunity. Remarkably, ZnMA achieves complete inhibition of lung metastasis via lymphatic-targeted immunomodulation, enhancing metastatic lymph node (LN) DC maturation and cytotoxic T cell infiltration. This work establishes a paradigm for carbon-based nanovaccine combining metal adjuvantation, targeting, and antigen presentation engineering to overcome tumor immunosuppression.

The emergence of second near-infrared (NIR-II, 1000–1700 nm) fluorescence imaging has revolutionized biomedical diagnostics and therapeutic monitoring by overcoming the limitations of conventional visible (400–700 nm) and NIR-I (700–900 nm) optical techniques. NIR-II light exhibits superior tissue penetration depth, reduced photon scattering, and minimized autofluorescence, enabling high-resolution imaging at centimeter depths with exceptional spatiotemporal resolution. These advantages have spurred intense research into developing advanced NIR-II light-activated fluorescent nanomaterials. Among these, organic semiconducting fluorophores (OSFs) have emerged as prominent candidates. Distinguished by their tunable molecular architectures and optoelectronic properties, strong molar extinction coefficients, exceptional fluorescence quantum efficiency, and robust chemical stability, OSFs have garnered substantial research attention and been extensively explored for applications in biomedical theranostics. Herein, this review offers a systematic overview of recent breakthroughs in engineering NIR-II-excitable OSFs for advanced NIR-II bioimaging and phototheranostic applications. The first section focuses on four key design methodologies to optimize NIR-II absorption/emission properties, containing regulation of intramolecular charge transfer, manipulation of molecular spatial configuration, a J-aggregation strategy, and formation of fluorophore-protein co-assembly complexes. The second section comprehensively classifies seven main types of OSFs with the different molecular architectures, and further analyzes their respective optical tunability and biological theranostic applications. By correlating molecular design principles with nanomaterial performance in deep-tissue imaging and theranostic integration, this review provides critical insights into structure-property-application relationships. Finally, we propose future directions for developing next-generation OSFs, aiming to bridge the gap between clinical translation and laboratory innovation in NIR-II bioimaging.

Semiconducting open-shell radicals (SORs) have promising potential for the development of phototheranostic agents, enabling tumor bioimaging and boosting tumorous reactive oxygen species (ROS). Herein, a new class of semiconducting perylene diimide (PDI), designated as PDI(Br)n with various numbers of bromine (Br) atoms modified on PDI's bay/ortho positions is reported. PDI(Br)n is demonstrated to transform into a radical anion, [PDI(Br)n]•-, in a reducing solution, with a typical g-value of 2.0022. Specifically, [PDI(Br)4/6]•- is generated in the weakly reductive tumor-mimicking solution and exhibits high stability in air. Quantum chemical kinetic simulation and ultrafast femtosecond transient absorption spectroscopy indicate that [PDI(Br)6]•- has a low π-π stacking energy (0.35 eV), a fast electron transfer rate (192.4 ps) and energy gap of PDI(Br)6 (ΔES1, T1 = 1.307 eV, ΔES1, T2 = 0.324 eV) respectively, which together result in excited-state charge transfer characters. The PDI(Br)6 nanoparticle radicals, [PDI(Br)6] NPs•-, specifically enable chemodynamic and type-I photodynamic ROS generation in tumors, including superoxide and hydroxyl radicals, which elicit immunogenic cell death effect. Also, [PDI(Br)6] NPs•- facilitate activatable bioimaging-guided therapy due to their photoacoustic signal at 808 nm and NIR-II emission at 1115 nm. The work paves the way for the design of SORs for precise cancer theranostics.