Thiolate-protected noble-metal clusters play essential roles in numerous applications, rendering this area one of the most vibrant research frontiers. The gold-hydrogen analogy has been firmly established in various hydrogen-atom-doped small gold clusters. In this work, we systematically investigate the chemical bonding characteristics in isolated model systems of [L-Au-SR]- (L = H and Au; R = H and CH3) complexes. By combining gas-phase negative ion photoelectron velocity-map imaging (NI-PEVMI) with density functional theory calculations, we demonstrate that the geometric and frontier molecular orbital properties of Au2SR- (R = H and CH3) closely mimic those of HAuSR- (R = H and CH3), respectively. Furthermore, our analyses reveal that the covalent character of the bonds is ligand-dependent and follows the trend: Au-H > Au-Au > Au-S.

Sepsis is a life - threatening systemic inflammatory response syndrome triggered by pathogenic infections, which is characterized by severe oxidative stress, immune dysregulation, and multiple organ dysfunction, accompanied by a high mortality rate. Its primary pathogenesis encompasses pathogen - induced immune overactivation, resulting in cytokine storms, oxidative damage, tissue injury, and organ failure. This research developed a bionic nanotherapeutic system for the treatment of sepsis. Cerium dioxide (CeO₂) nanoparticles with inherent antioxidant activity were employed as carriers, loaded with the broad - spectrum antibiotic imipenem - cilastatin sodium hydrate (IC), and further coated with macrophage membranes (MM). The MM conferred immune evasion, homologous targeting, and lipopolysaccharide (LPS) - neutralizing capabilities to the nanosystem.This integrated platform combines CeO₂ - mediated reactive oxygen species (ROS) scavenging, antibiotic - induced bactericidal effects, and MM - mediated inflammatory regulation. In vitro investigations verified its potent ROS - scavenging, LPS - neutralizing, anti - inflammatory, and antibacterial activities. In a cecal ligation and puncture (CLP) - induced mouse sepsis model, IC@CeO₂@MM effectively reduced both systemic and local inflammatory cytokines, alleviated multi - organ injury in the liver, kidneys, and intestines, and enhanced survival rates. Mechanistically, it maintained mitochondrial membrane potential and decreased mitochondrial ROS (mtROS) accumulation in macrophages.This synergistic strategy simultaneously achieves antibacterial, antioxidant, and immunomodulatory effects, presenting a promising and novel approach for the comprehensive management of sepsis.

Vaccines establish humoral protection via neutralizing antibodies, which are sustained by bone marrow long-lived plasma cells (LLPC). The lifespan of LLPCs determines the duration of protection, however, the mechanisms underlying LLPC survival remain poorly understood. Here, we employ plasma cell-specific conditional knockout mice to systematically dissect the roles of receptors for candidate niche factors. Unexpectedly, we find that the cytokine receptor TACI is essential for LLPC survival. Loss of TACI reduces polyclonal plasma cell numbers and abrogated LLPCs induced by both T cell-dependent and T cell-independent antigens. Importantly, TACI deficiency severely compromises protection elicited by both SARS-CoV-2 and influenza vaccines. Mechanistically, loss of TACI causes accumulation of mitochondrial reactive oxygen species and subsequent plasma cell death. Importantly, pharmacologic antioxidant treatment with the FDA-approved drug, N‑acetylcysteine, mitigates ROS accumulation, rescues LLPC numbers, and enhances influenza vaccine efficacy in vivo. Together, these results establish TACI as a non-redundant regulator of LLPC longevity and vaccine-induced protection by limiting oxidative stress, providing a potential target for enhancing vaccine efficacy and durability.

Osteosarcoma, the most prevalent malignant bone tumor in adolescents, presents significant clinical challenges due to its aggressive nature and resistance to conventional therapies including radiotherapy. Through analysis of human osteosarcoma specimens, we identified lactate and TGF(3 as key regulators of the tumor microenvironment (TME), which collectively induce an immunosuppressive osteosarcoma microenvironment. To address this, we developed a novel multifunctional nanosystem constructed by genetically engineering lactate oxidase (LOX)-anchored platelet membranes to encapsulate manganese dioxide (MnO2) nanoparticles and the TGF(3 inhibitor SB525334. This system demonstrates tumor-selective accumulation while simultaneously enabling lactate catabolism and TGF(3 suppression. In vitro and in vivo studies confirmed that this synergistic approach effectively inhibits TGF(3-mediated signaling pathways and enhances T cell-mediated anti-tumor immunity. Furthermore, combination therapy with PD-L1 blockade significantly suppressed tumor growth and reduced recurrence rates, demonstrating robust adaptive immune responses. These findings highlight the transformative potential of engineered platelet membrane nanosystems in integrating metabolic modulation with immune regulation to improve current osteosarcoma treatment paradigms.

Osteosarcoma (OS) remains the most common primary bone malignancy in children and adolescents. Despite advances in neoadjuvant chemotherapy, metastasis and recurrence constitute major clinical challenges. Zinc oxide nanoparticles (ZnO NPs) possess promising anticancer activity, yet their anti-metastatic mechanisms in OS remain unclear. Here, we reported a novel bio-inspired strategy using exosomes derived from ZnO NP-treated OS cells (ZnO-Exos), that significantly suppressed cell viability, migration, and invasion in OS cells. Mechanistically, ZnO-Exos-derived Zn2 + ions activated and stabilized hypoxia-inducible factor-1 alpha (HIF-1 alpha), which transcriptionally upregulated the expression of exosomal miR-1287-5p, and then in turn directly targeted and downregulated the mRNA of Snail, a master transcriptional repressor driving epithelial-mesenchymal transition (EMT). In an orthotopic OS mouse model, intratumoral injection of ZnO-Exos significantly inhibited primary tumor growth and spontaneous lung metastasis, extended survival, and exhibited excellent biocompatibility. Collectively, this study elucidated a novel ZnO NP-educated exosomes that exert anti-metastatic effects, offering a targeted, low-toxicity strategy for OS therapy and metastasis inhibition through Zn2+/HIF-1 alpha/miR-1287-5p/ Snail axis.

With the acceleration of global industrialization, water treatment has emerged as a critical environmental challenge demanding urgent resolution. Metal-organic frameworks (MOFs), characterized by their ultrahigh specific surface areas, tunable porous architectures, and multifunctional active sites, are regarded as highly promising materials for water-treatment applications. However, the practical implementation of MOFs and their derivatives remains constrained. Although recent advances in synthetic strategy optimization have significantly enhanced their water-treatment performance, precise elucidation of material intrinsic characteristics continues to pose challenges. Conventional characterization techniques struggle to reveal critical information regarding dynamic structural evolution in aqueous environments, local defect distribution, and electronic states of active sites, thereby hindering atomic/molecular-scale theoretical guidance for performance optimization. Synchrotron radiation techniques, leveraging their advantages of high flux, exceptional resolution, and element-specific detection capabilities, provide unique solutions to overcome these limitations. These advanced methodologies enable accurate correlation between MOF synthetic strategies and water treatment performance metrics, offering crucial experimental insights for rational material design. This review systematically compares the impact of synthesis and modification strategies on the water treatment performance of MOFs and their derivatives. By employing synchrotron radiation characterization techniques to elucidate the "structure-property" relationships relevant to water treatment, this work provides a theoretical foundation and technical support for the targeted synthesis, performance optimization, and industrial translation of high-performance MOF-based materials.

Boron is a naturally occurring trace element with multifaceted biological effects in both humans and animals. Its health impact follows a U-shaped dose-response curve, where both deficiency and excess (≥ 100 mg/day) are detrimental. Boron exerts diverse biological effects across multiple organ systems, including promoting bone formation, reducing cardiac fibrosis, supporting liver and brain function, and modulating immune responses. Its mechanisms of action involve regulating key enzymes like vitamin D-metabolizing hydroxylases, stabilizing mitochondrial membranes, and influencing cell proliferation pathways. Additionally, boron demonstrates antimicrobial properties against various pathogens and enhances wound healing through anti-inflammatory and antioxidant activities. These multifaceted functions are consistently dose-dependent, with beneficial effects occurring at optimal levels while excess intake causes toxicity across different tissues. Boron is a crucial trace element with significant and diverse physiological roles. Its effects are highly dose-dependent, underscoring the need for a defined optimal intake range. Future research should focus on determining its precise bioavailability and toxicity, establishing species-, age-, and sex-specific dietary requirements, and further elucidating its molecular mechanisms to develop safe and effective boron-based therapeutic strategies.

Immunotherapy for bladder cancer remains limited by immunosuppressive tumor microenvironment (TME) and low immunogenicity. Here, we developed a TME-responsive bimetallic porous nanozyme, Fe/Cu-HPC@GOx/PEG, to synergistically induce dual ferroptosis/cuproptosis and amplify antitumor immunity. The nanozyme integrates Fe-Cu bimetal catalytic centers within a hierarchical porous carbon framework, enabling glucose oxidase (GOx)-triggered H₂O₂ generation and subsequent Fenton/Fenton-like reactions. In vitro studies demonstrated that the nanozyme effectively depleted glutathione, inactivated GPX4, and accumulated lipid peroxides to drive ferroptosis. Concurrently, hypoxia alleviation via O₂ generation suppressed HIF-1α-mediated glycolysis, blocked ATP7B-dependent Cu⁺ efflux, and triggered DLAT lipoylation, leading to cuproptosis. Mitochondrial dysfunction from dual cell death pathways synergistically enhanced oxidative stress and immunogenic cell death (ICD), evidenced by calreticulin exposure, HMGB1/ATP release, and dendritic cells maturation. In vivo, Fe/Cu-HPC@GOx/PEG significantly suppressed tumor growth and remodeled the TME, with increased CD8⁺ T cell infiltration and elevated pro-inflammatory cytokines. Systemic toxicity evaluation confirmed biocompatibility, showing no organ damage or biochemical abnormalities. This work presents a paradigm-shifting strategy that leverages metal ion-mediated dual death pathways to overcome immunotherapy resistance, offering a clinically translatable nanoplatform for precision oncology.

The specific activation of dendritic cells (DCs) and tumor-associated macrophages (TAMs) can activate innate and adaptive immune responses to reverse the tumor immunosuppressive microenvironment. In this study, manganese ferrite nanohybrid MnFe5O8@(M1M-DOX) is synthesized to activate cGAS-STING and NF-κB crosstalk in DCs and TAMs. MnFe5O8, as the source of Fe2+/Fe3+ and Mn2+, is encapsulated with a microdose of doxorubicin (DOX) using an M1 macrophage cytomembrane. Fe2+/Fe3+ and DOX can cooperatively induce tumorous ferroptosis, triggering immunogenic cell death (ICD) that exposes tumor antigens. The release of Fe2+/Fe3+ and Mn2+ has intrinsic dual-immunomodulatory effects on the activation of DCs and the reprogramming of TAMs from the M2 to M1 phenotype. Briefly, Fe2+/Fe3+ activates the NF-κB signaling pathway to trigger the activation of STING signaling. Meanwhile, Mn2+ further enhances the activation of STING and stimulates NF-κB in a cascade-activating manner. Thus, the mutually reinforcing dual activation of cGAS-STING and NF-κB crosstalk prompts the strong maturation of DCs and TAMs, synergistically promoting the infiltration of T cells to inhibit primary tumor growth and localized recurrence. This work proposes a strategy for delivering immunomodulatory metal ions in nanoalloy and harnessing the activation of multisignaling pathways in antigen-presenting cells (APCs) to provide perspectives for tumor immunotherapy.

There is a critical need for inclusive diagnostic platforms to enhance the accuracy of early breast cancer detection. Dysregulated microRNA-1246 (miR-1246), closely linked to the disease progression and recurrence, has emerged as a promising diagnostic and prognostic biomarker for BC. However, achieving simple, rapid, and ultrasensitive quantification of serum miRNAs remains significant challenge. In this study, we present an innovative detection platform triggered by endogenous DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1). This platform utilizes an oligonucleotide probe with variable modified AP sites (denoted as AOP) coupled with graphene oxide (GO) for quantifying miR-1246. Our in vitro experiments reveal that the proposed method employing the AOP2 probe with two AP sites exhibits exceptional selectivity and sensitivity. The method achieves a detection limit as low as 2.3 pM towards miR-1246, which is approximately 260-fold more sensitive than the enzyme-free system. RT-qPCR experiments further validate the accuracy and practicability of the AOP2-based platform. In clinical trials, our platform has successfully differentiated between BC patients and normal healthy controls. In conclusion, we have established an integrated biosensing technology for PCR-free, non-invasive liquid biopsies of miR-1246, offering a promising approach for BC diagnosis.

This study presents a simple strategy to develop a tumor‐acidity responsive core‐crosslinked micellar nanoassembly capable of delivering multiple drugs to combat drug resistance. Paclitaxel (PTX) nanocrystals are prepared using D‐α‐tocopherol polyethylene glycol 1000 succinate (TPGS) as an emulsifier and cross‐linked with poly(β‐cyclodextrin) (PCD) to form the core. An acid‐labile prodrug, poly(ethylene glycol)‐doxorubicin (mPEG‐DOX), is utilized as the shell, forming a core‐shell nanoassembly (CSNA) via supramolecular interactions. The CSNA demonstrated high stability in aqueous and serum environments, with triggered shell‐detachment in response to tumor acidity. The nanomedicine exhibited superior inhibition of drug‐resistant cancer cell line MCF‐7/ADR compared to DOX or PTX alone, offering potential to overcome drug resistance in chemotherapy.

The solubility of 2,2 ',4,4 ',6,6 '-hexanitrobibenzyl in eleven pure solvents (acetone, cyclohexanone, 2-butanone, methyl acetate, ethyl acetate, benzene, chlorobenzene, pyridine, acetonitrile, 1,2-dichloroethane and 1,4-dioxane) was measured by laser dynamic method at the temperature range from 293.15 K to 333.15 K under the pressure of 101.3 kPa. The study found that the solubility of 2,2 ',4,4 ',6,6 '-hexanitrobibenzyl is positively correlated with increasing temperature. The experimental data were correlated using four thermodynamic models: the modified Apelblat model, van't Hoff model, NRTL model, and Wilson model. The modified Apelblat model demonstrated superior correlation performance. Hirshfeld surface and molecular electrostatic potential surface analysis were also conducted to investigate the solvent-solute interaction sites and the effects of interactions on the solubility of 2,2 ',4,4 ',6,6 '-hexanitrobibenzyl in eleven selected pure solvents. Additionally, the thermodynamic properties of the dissolution process were calculated using the van't Hoff model, and the results indicated that the dissolution of 2,2 ',4,4 ',6,6 '-hexanitrobibenzyl in eleven selected pure solvents is an endothermic and entropy-increasing process.

The integration of ferroptosis induction with cancer immunotherapy has emerged as a promising approach in oncology, offering dual mechanisms to overcome therapeutic resistance and tumor heterogeneity. Nevertheless, the dynamic and complicated crosstalk between ferroptosis processes and immune regulation in tumor microenvironments presents both opportunities and challenges. By inducing lipid peroxidation in tumor tissues, ferroptotic tumor cell death can stimulate immunogenicity. Nevertheless, excessive lipid peroxidation may paradoxically impair the functionality of multiple immune cells, thereby presenting crosstalk challenges in therapeutic strategies. To address these crosstalk challenges, several advanced drug delivery strategies have been proposed, such as immunostimulatory active pharmaceutical ingredients co-delivery, tumor-targeted delivery, and stimuli-responsive delivery. These drug delivery strategies demonstrate dual therapeutic efficacy by synergistically potentiating ferroptosis induction in malignant cells while concurrently mitigating immunotoxicity and even augmenting antitumor immunity. This review offers detailed insights into the crosstalk between ferroptosis and tumor immunity, along with a guiding overview of the three delivery strategies. The current obstacles and translational potential were thoroughly analyzed, providing valuable perspectives for future research.

Enhancing cancer immunotherapy using methods that induce immunogenic cell death (ICD) can significantly improve its effectiveness and profoundly influence its role as a highly efficient cancer treatment strategy. However, the limited penetration of cytotoxic T cells into tumors, owing to dense tumor fibrosis, remains a significant barrier to immunotherapy. A tumor microenvironment-sensitive intelligent dual-drug delivery system was developed to simultaneously deliver epigallocatechin-3-gallate (EGCG) and doxorubicin (DOX) to mitochondria. EGCG enhanced the mitochondria-targeted action of DOX and increased damage to the mitochondrial electron transport chain which facilitated capturing electrons in the mitochondrial matrix of DOX. Subsequently, DOX molecules form a semiquinone intermediate and electrons are transferred to oxygen to generate reactive oxygen species (ROS) that induce mitochondrial apoptosis. These results indicate that EGCG amplifies the combined effects of chemo/chemodynamic therapy of DOX, demonstrating a pronounced synergistic ICD effect that recruits CD8+ T cells to the tumor microenvironment (TME). In addition, EGCG promotes T-cell infiltration into tumor tissues by inhibiting the transforming growth factor-β signaling pathway, thereby significantly enhancing antitumor efficacy. This study advances the efficacy of immunotherapy through bidirectional synergy, which not only enhances intrinsic tumor immunogenicity but also overcomes the extrinsic physical barriers of tumors, providing a new direction for the development of broadly applicable immunotherapies.

Metal-organic framework (MOF)-derived materials have emerged as highly efficient catalysts for peroxymonosulfate (PMS) activation, yet their role in regulating reactive oxygen species (ROS) remains poorly understood. Catalysts synthesized at a 5 degrees C/min heating rate and 750 degrees C pyrolysis temperature significantly enhanced PMS activation, achieving 96 % antipyrine removal within 60 min with a reaction rate constant of 0.053 min(-1). These catalysts demonstrated sustained activity for 300 min and exhibited robust performance across pH 3---11 in various aqueous environments. Singlet oxygen (O-1(2)), hydroxyl radicals (OH), and sulfate radicals (SO4-) were identified as the primary ROS, contributing 59.6 %, 35.1 %, and 5.3 % respectively, to antipyrine removal. Density functional theory calculations revealed that Fe3C/pyrrolic N-doped graphene (PlNG) heterojunctions had superior adsorption among 19 materials, facilitating adsorption-dissociation-desorption. PMS adsorption energy correlated linearly with Bader charge transfer. ROS generation patterns were similar on PlNG, Fe/PlNG, and Fe3C/PlNG, but Fe3O4/PlNG exhibited distinct behavior, with O- being most easily generated, followed by OH, and SO4- being least likely. The rate-limiting steps for ROS generation varied, highlighting the importance of selecting the right catalyst for effective ROS production during PMS activation. Fe3C/PING and PING relied on van der Waals forces and hydrogen bonds for PMS, while Fe/PING and Fe3O4/PING depended solely on van der Waals forces. The strength order of van der Waals forces was Fe3C/PING > PING > Fe/PING > Fe3O4/PING, affecting adsorption energy and ROS generation. This study elucidates the pivotal role of MOF-derived materials in ROS generation, offering new insights for optimizing water purification processes.

G-quadruplexes are four-stranded nucleic acid structures that play vital roles in regulating gene expression, maintaining genomic stability, and supporting various biological processes. This protocol details their formation from double-stranded DNA via in vitro transcription. It includes steps for selecting suitable DNA templates, assembling necessary components (such as RNA polymerase, nucleotides, and buffers), setting optimal incubation conditions, and performing dimethyl sulfate (DMS) footprinting to analyze the structures. For complete details on the use and execution of this protocol, please refer to Zhang et al.1 and Gong et al.2.

The immunosuppressive tumor microenvironment (TME) of osteosarcoma (OS) results in an unsatisfactory conventional therapeutic effect. While chemotherapy-induced apoptosis fails to fully activate antitumor immunity due to inadequate release of tumor-associated antigens (TAAs) and enhanced efferocytosis by tumor-associated macrophages (TAMs), we propose to remodel the TME by inducing immunogenic cell death, including pyroptosis and necroptosis, coupled with inhibition of TAMs efferocytosis. Specifically, we constructed a piezoelectric catalyst, BFO@CaO2-TPP (BCT), which targets mitochondria. Under ultrasound, BCT generated reactive oxygen species (ROS) by enhancing the Fenton reaction and released Ca2+ to trigger mitochondrial calcium overload, which synergistically activated the caspase-3/GSDME nonclassical pyroptosis pathway and prompted the release of proinflammatory molecules from tumor cells. Concurrently, BCT disrupts mitochondrial oxidative phosphorylation (OXPHOS) in TAMs, inhibits their efferocytotic capacity. More importantly, these functionally altered TAMs facilitate increased GSDME expression and TNF/TNFR1 signaling in osteosarcoma cells, favoring pyroptosis and necroptosis. This dual regulation, both endogenous and exogenous ultimately transforms the 'cold' TME into a 'hot' state, as validated in patient-derived organoids, demonstrating significant translational potential.

Combination of chemotherapy and cancer immunotherapy has shown substantial clinical promise. However, the immunosuppressive tumor microenvironment (TME) poses a critical barrier to this combination therapy. Here, a tumor lysosome-targeted immunomodulatory strategy based on a biomimetic nanoadjuvant is presented, which effectively overcomes the immunosuppressive TME and demonstrates enhanced therapeutic efficacy when combined with chemotherapy. This nanoadjuvant integrates Fe-DOX coordination nanoparticles, a MnCO3 shell, TLR7/8 agonist (R848), and a mature dendritic cell membrane (DCM) coating. The resulting DCM@(Fe-DOX-Mn-R848) nanoadjuvant induces immunogenic cell death in tumor cells via lysosomal-mitochondrial cascade destruction. Concurrently, it activates the cGAS-STING signaling pathway to promote dendritic cell maturation and repolarize tumor-associated macrophages from M2 to M1 phenotype, thereby effectively enhancing CD8+ T cell activation and tumor therapeutic efficacy. When combined with PD-L1 blockade therapy, the nanoadjuvant demonstrates enhanced efficacy in murine models of primary and recurrent triple-negative breast cancer, establishing durable immune memory. This platform demonstrates significant potential in overcoming immunosuppressive TME and advancing combination therapy through lysosome-targeting drug delivery technology, revealing promising prospects for cancer treatment.