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Ferroptosis, an iron‐ and reactive oxygen species (ROS)‐dependent cell death, holds significant promise for tumor therapy due to its ability to induce lipid peroxidation (LPO) and trigger antitumor immune responses. However, elevated cholesterol levels in cancer cells impede ferroptosis and compromise immune function. Here, a novel nanozyme, Fe‐MOF/CP, composed of iron metal‐organic framework (Fe‐MOF) nanoparticles loaded with cholesterol oxidase and PEGylation for integrated ferroptosis and immunotherapy is introduced. Fe‐MOF/CP depletes cholesterol and generates hydrogen peroxide, enhancing ROS levels and inducing LPO, thereby promoting ferroptosis. This process disrupts lipid raft integrity and downregulates glutathione peroxidase 4 and ferroptosis suppressor protein 1, further facilitating ferroptosis. Concurrently, Fe‐MOF/CP augments immunogenic cell death, reduces programmed death‐ligand 1 expression, and revitalizes exhausted CD8+ T cells. In vivo studies demonstrate significant therapeutic efficacy in abscopal, metastasis, and recurrent tumor models, highlighting the robust antitumor immune responses elicited by Fe‐MOF/CP. This study underscores the potential of Fe‐MOF/CP as a multifunctional therapeutic agent that combines ferroptosis and immunotherapy, offering a promising strategy for effective and durable cancer treatment. This work presents a hybrid nanozyme composed of PEGylated Fe‐MOF nanoparticles and cholesterol oxidase, termed Fe‐MOF/CP, designed to initiate combinatorial tumor ferroptosis immunotherapy. The findings indicate that cholesterol depletion not only enhances the catalytic efficiency of the nanozyme but also augments tumoral ferroptosis and antitumor immune responses, highlighting the significant potential of cholesterol modulation in cancer treatment.

Our retrospective cohort study (3-9 years) describes the progression and regression patterns among working adults aged 18-65 with normoglycemia, prediabetes, and diabetes, providing evidence for diabetes prevention and management strategies in this population. 15,765 subjects received baseline examinations between 2014 and 2018, with 14,623 (92.7%) completing follow-up, representing a follow-up period of 3-9 years for analysis. Chi-square tests were used to compare prediabetes and diabetes incidence, as well as rates of glycemic normalization among different age groups and genders in working populations. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI). Among participants with baseline normoglycemia, 23.9% progressed to prediabetes, and 2.3% developed diabetes. Among prediabetic individuals, 28.0% progressed to diabetes, and 18.7% reverted to normoglycemia. Younger adults (18-40 years) exhibited significantly lower progression rates from normoglycemia to both prediabetes and diabetes compared to middle-aged adults (40-65 years) (prediabetes: 15.8% vs. 37.8%; diabetes: 1.2% vs. 4.2%; P < 0.001). Cox models revealed that young prediabetic individuals had a significantly higher risk of developing diabetes than middle-aged prediabetic individuals, showing a pronounced age-dependent risk pattern: prediabetic individuals aged 18-40 had an adjusted hazard ratio (HR) of 22.1 (95% CI: 14.9-32.7), compared to HR = 9.12 (7.45-11.2) in those aged 40-65. Prediabetes among working-age adults, particularly in younger individuals (18-40 years), carries an exceptionally elevated risk of progression to diabetes. The observed sex disparities in progression among young adults highlight the need for age- and sex-specific prevention strategies.

Development of ferroptosis-inducible nanoplatforms with high efficiency and specificity is highly needed and challenging in tumor ferrotherapy. Here, we demonstrate highly effective tumor ferrotherapy using iron (II)-based metal-organic framework (Fe ss MOF) nanoparticles, assembled from disulfide bonds and ferrous ions. The as-prepared Fe ss MOF nanoparticles exhibit peroxidase-like activity and pH/glutathione-dependent degradability, which enables tumor-responsive catalytic therapy and glutathione depletion by the thiol/disulfide exchange to suppress glutathione peroxidase 4, respectively. Upon PEGylation and Actinomycin D (ActD) loading, the resulting Fe ss MOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc − system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the Fe ss MOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.

Photodynamic therapy (PDT) is a promising strategy for tumor treatment. Still, its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels. Here, we fabricated a novel nanoenzyme that derived from metal-organic framework (MOF) with intrinsic catalase-like activities to decompose H 2 O 2 to O 2 and simultaneous glutathione consumption for enhancing PDT efficacy. The obtained Mn 3 O 4 nanoparticle shows a larger pore size and surface area compared to native MOF particles, which can be used to load high dose photosensitizer. When decorated with AS1411 aptamer and polyethylene glycol (PEG), the obtained Mn 3 O 4 -PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability. Remarkably, Mn 3 O 4 -PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity. This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT. It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.

The discovery of Nb-W-O materials years ago marks the milestone of charging a lithium-ion battery in minutes. Nevertheless, for many applications, charging lithium-ion battery within one minute is urgently demanded, the bottleneck of which largely lies in the lack of fundamental understanding of Li + storage mechanisms in these materials. Herein, by visualizing Li + intercalated into representative Nb 16 W 5 O 55 , we find that the fast-charging nature of such material originates from an interesting rate-dependent lattice relaxation process associated with the Jahn-Teller effect. Furthermore, in situ electron microscopy further reveals a directional, [010]-preferred Li + transport mechanism in Nb 16 W 5 O 55 crystals being the “bottleneck” toward fast charging that deprives the entry of any desolvated Li + through the prevailing non-(010) surfaces. Hence, we propose a machine learning-assisted interface engineering strategy to swiftly collect desolvated Li + and relocate them to (010) surfaces for their fast intercalation. As a result, a capacity of ≈ 116 mAh g −1 (68.5% of the theoretical capacity) at 80 C (45 s) is achieved when coupled with a Li negative electrode. Nb-W-O materials enable rapid Li⁺ storage, yet sub-minute charging remains unlocked. Here, the authors investigate fast-charging of Nb 16 W 5 O 55 cathode, revealing rate-dependent lattice relaxation and [010]-preferred Li⁺ transport, proposing interface engineering to enhance intercalation and achieve ~116 mAh g⁻¹ at 80 C in 45 s.

Elevated copper levels induce tumor cuproptosis and ferroptosis, leading to immunogenic cell death and subsequent antitumor immune responses. However, dysregulated copper metabolism in tumor cells maintains homeostatic copper balance, while hypoxic microenvironments hinder therapeutic efficacy. In this study, we present a nanozyme system, termed Cu ss OMEp, comprising a copper-based nanovector (Cu ss NV) that is PEGylated and loaded with omeprazole, a copper transporter inhibitor, to enhance tumor synergistic immunotherapy by promoting cuproptosis and ferroptosis. Cu ss NV is assembled from dithiodiglycolic acid and copper ions, exhibiting peroxidase, glutathione oxidase, and catalase-like activities, along with responsive degradability. This nanozyme alleviates tumor hypoxia by producing oxygen, induces ferroptosis through the generation of lethal hydroxyl radicals, and depletes glutathione. Additionally, omeprazole increases cellular copper concentration and oxidative stress by inhibiting the intracellular copper-transporting ATPase 1 (ATP7A), enhancing lipoylated protein oligomerization and cuproptosis. In a breast tumor mouse model, Cu ss OMEp elicits robust antitumor immune responses, including dendritic cell maturation and T cell proliferation. When combined with PD-1 antibodies (αPD-1), Cu ss OMEp significantly inhibits tumor metastasis in bilateral and lung metastatic models. This work presents a functional nanozyme system as a promising strategy for synergistic tumor immunotherapy leveraging ferroptosis and cuproptosis Graphical abstract

E-mail has become the main carrier of spreading malicious software and been widely used for phishing, even high-level persistent threats. The e-mail accounts with high social reputation are primary targets to be attacked and utilized by attackers, suffering a lot of probing attacks for a long time. In this paper, in order to understand the probing pattern of the e-mail account attacks, we analyse the log of email account probing captured in the campus network based on graph mining. By analysing characteristics of the dataset in different dimensions, we find a kind of e-mail account probing attack and give it a new definition. Based on the analysis results, its probing pattern is figured out. From the point of probing groups and individuals, we find definitely opposite characteristics of the attack. Owing to the probing pattern and its characteristics, attacks can escape from the detection of security devices, which has a harmful effect on e-mail users and administrators. The analysis results of this paper provide support for the detection and defence of such distributed attacks.

The serious lack of policy implementation of village-level river chiefs has had a negative impact on the environmental governance of rivers and lakes in the village area. Environmental regulation plays an important role in the implementation of village-level river chief policies, and the mechanism by which they affect the policy implementation capacity has become an important topic worth exploring. This paper takes 18 village-level river chiefs from 7 provinces (autonomous regions) in Jiangsu, Zhejiang, Hebei, Hubei, Anhui, and Shaanxi as research objects, and uses the programmatic grounding theory to carry out an exploratory analysis around the core theme of “environmental regulation empowers the policy implementation capacity of village-level River Chiefs”. The results of the code showed that: Environmental regulation will have an impact on the policy implementation capacity of village-level river chiefs; Environmental regulation can affect the policy implementation capacity of village-level river chiefs by influencing the environmental literacy and cooperation level of village-level river chiefs. The individual characteristics of village-level river chiefs and the characteristics of their villages are the factors influencing the policy implementation capacity of village-level river chiefs. The public service motivation of village-level river chiefs will regulate the impact of environmental regulation on their policy implementation capacity. The conclusion of the study suggested that it is necessary to pay attention to the important role of environmental regulation, formulating specific and feasible environmental regulation by classification and accuracy, stimulating the public service motivation of village river chiefs, improving the environmental literacy of village river chiefs, strengthening the coordination and linkage between village river chiefs and different subjects, and improving the level of cooperation between village river chiefs, promoting the improvement of the policy implementation capacity of village river chiefs.

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/μl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.