Encapsulation engineering of porous crystalline frameworks for delayed luminescence and circularly polarized luminescence.

Delayed luminescence (DF), including phosphorescence and thermally activated delayed fluorescence (TADF), and circularly polarized luminescence (CPL) exhibit common and broad application prospects in optoelectronic displays, biological imaging, and encryption. Thus, the combination of delayed luminescence and circularly polarized luminescence is attracting increasing attention. The encapsulation of guest emitters in various host matrices to form host-guest systems has been demonstrated to be an appealing strategy to further enhance and/or modulate their delayed luminescence and circularly polarized luminescence. Compared with conventional liquid crystals, polymers, and supramolecular matrices, porous crystalline frameworks (PCFs) including metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), zeolites and hydrogen-bonded organic frameworks (HOFs) can not only overcome shortcomings such as flexibility and disorder but also achieve the ordered encapsulation of guests and long-term stability of chiral structures, providing new promising host platforms for the development of DF and CPL. In this review, we provide a comprehensive and critical summary of the recent progress in host-guest photochemistry via the encapsulation engineering of guest emitters in PCFs, particularly focusing on delayed luminescence and circularly polarized luminescence. Initially, the general principle of phosphorescence, TADF and CPL, the combination of DF and CPL, and energy transfer processes between host and guests are introduced. Subsequently, we comprehensively discuss the critical factors affecting the encapsulation engineering of guest emitters in PCFs, such as pore structures, the confinement effect, charge and energy transfer between the host and guest, conformational dynamics, and aggregation model of guest emitters. Thereafter, we summarize the effective methods for the preparation of host-guest systems, especially single-crystal-to-single-crystal (SC-SC) transformation and epitaxial growth, which are distinct from conventional methods based on amorphous materials. Then, the recent advancements in host-guest systems based on PCFs for delayed luminescence and circularly polarized luminescence are highlighted. Finally, we present our personal insights into the challenges and future opportunities in this promising field.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Cultivating High-Performance Flexible All-in-One Supercapacitors with 3D Network Through Continuous Biosynthesis.

Flexible supercapacitors are potential to power next-generation flexible electronics. However, the mechanical and electrochemical stability of flexible supercapacitors under different flexible conditions is limited by the weak bonding between adjacent layers, posing a significant hindrance to their practical applicability. Herein, based on the uninterrupted 3D network during the growth of bacterial cellulose (BC), w e have cultivated a flexible all-in-one supercapacitor through a continuous biosynthesis process. This strategy ensures the continuity of the 3D network of BC throughout the material, thereby forming a continuous electrode-separator-electrode structure. Benefitting from this bioinspired structure, the all-in-one supercapacitor not only achieves a high areal capacitance (3.79 F cm-2) of electrodes but also demonstrates the integration of high tensile strength (2.15 MPa), high shear strength (more than 54.6 kPa), and high bending resistance, indicating a novel pathway towards high-performance flexible power sources. This article is protected by copyright. All rights reserved.

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment.

BACKGROUND: Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC). METHODS: We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC. RESULTS: The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells. CONCLUSION: ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.

CovEpiAb: a comprehensive database and analysis resource for immune epitopes and antibodies of human coronaviruses.

Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes. Thus, we constructed CovEpiAb, a comprehensive database and analysis resource of human coronavirus (HCoVs) immune epitopes and antibodies. CovEpiAb contains information on over 60 000 experimentally validated epitopes and over 12 000 antibodies for HCoVs and SARS-CoV-2 variants. The database is unique in (1) classifying and annotating cross-reactive epitopes from different viruses and variants; (2) providing molecular and experimental interaction profiles of antibodies, including structure-based binding sites and around 70 000 data on binding affinity and neutralizing activity; (3) providing virological characteristics of current and past circulating SARS-CoV-2 variants and in vitro activity of various therapeutics; and (4) offering site-level annotations of key functional features, including antibody binding, immunological epitopes, SARS-CoV-2 mutations and conservation across HCoVs. In addition, we developed an integrated pipeline for epitope prediction named COVEP, which is available from the webpage of CovEpiAb. CovEpiAb is freely accessible at https://pgx.zju.edu.cn/covepiab/.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5 mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.

An imbalanced GLP-1R/GIPR co-agonist peptide with a site-specific N-terminal PEGylation to maximize metabolic benefits.

Glycemic and body weight control gained from GLP-1R agonists remains an unmet need for diabetes and obesity treatment, leading to the development of GLP-1R/GIPR co-agonists. An imbalance in GLP-1R/GIPR agonism may extensively maximize the glucose- and weight-lowering effects. Hence, we prepared a potent and imbalanced GLP-1R/GIPR co-agonist, and refined its action time through a site-specific N-terminal PEGylation strategy. The pharmacological efficacy of these resulting long-acting co-agonists was interrogated both in vitro and in vivo. The results showed that peptide 1 possessed potent and imbalanced receptor-stimulating potency favoring GIP activity, but its hypoglycemic action was disrupted probably resulting from its short half-life. After PEGylation to improve the pharmacokinetics, the pharmacological effects were amplified compared to native peptide 1. Among the resulting derivatives, D-5K exhibited significant glycemic, HbA1c, body-weight, and food-intake control, outperforming GLP-1R mono-agonists. Based on its excellent pharmacological profiles, D-5K may hold the great therapeutic potential for diabetes and obesity treatment.

Global level of methylation in the sea lamprey (jawless vertebrate) genome is intermediate between invertebrate and jawed vertebrate genomes.

In eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. In invertebrate, methylated cytosine generally located on specific genomic elements (e.g., gene bodies and silenced repetitive elements) to show a "mosaic" pattern. While in jawed vertebrate (teleost and tetrapod), highly methylated cytosine located genome-wide but only absence at regulatory regions (e.g., promoter and enhancer). Many studies imply that the evolution of DNA methylation reprogramming may have helped the transition from invertebrates to jawed vertebrates, but the detail remains largely elusive. In this study, we used the whole-genome bisulfite-sequencing technology to investigate the genome-wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant agnathan (jawless) vertebrate. Strikingly, we found that the methylation level of the sea lamprey is very similar to that in sea urchin (a deuterostome) and sea squirt (a chordate) invertebrates. In sum, the global pattern in sea lamprey is intermediate methylation level (around 30%), that is higher than methylation level in the genomes of pre-bilaterians and protostomes (1%-10%), but lower than methylation level appeared in jawed vertebrates (around 70%, teleost and tetrapod). We anticipate that, in addition to genetic dynamics such as genome duplications, epigenetic dynamics such as global methylation reprograming was also orchestrated toward the emergence and evolution of vertebrates.

Synergistic Interaction between Metal Single-Atoms and Defective WO3- x Nanosheets for Enhanced Sonodynamic Cancer Therapy.

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO3- x nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO3 and OV-rich WO3- x nanosheets are first prepared by simple calcination of the WO3 ·H2 O nanosheets under an air and N2 atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO3- x nanosheets to obtain metal SA-decorated WO3- x nanocomposites (M-WO3- x ). Importantly, the Cu-WO3- x sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO3- x and Cu SA-decorated WO3 , which is also higher than other M-WO3- x nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO3- x nanosheets should be attributed to the synergistic effect between Cu SAs and WO3- x OVs. Therefore, after polyethylene glycol modification, the Cu-WO3- x can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO3- x -mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.

Malassezia infection associated with stucco keratosis.

We report a case of a 20-year-old young woman with a large stucco keratosis in the mons veneris, one of the clinical variants of Seborrheic keratoses (SKs). Periodic acid-Schiff staining revealed a large number of Malassezia spores in the stratum corneum. After oral antifungal treatment with itraconazole for 4 weeks, the benign tumor was completely cleared without residue or recurrence, which may open a new perspective for exploring the pathogenesis of SKs.

Development of an RBD-Fc fusion vaccine for COVID-19.

Although the global pandemic of SARS-CoV-2 has passed, there are still regional outbreaks that continue to jeopardize human health. Hence, there is still a great deal of interest in developing an efficient vaccine that can quickly and effectively prevent reemerging outbreaks of SARS-CoV-2. Delta variant was once a dominant strain in the world in 2021, and we first constructed a recombinant RBDdelta-Fc fusion vaccine by coupling the RBD of Delta variant with the human Fc fragment. This Fc fusion strategy increases the immunogenicity of the recombinant RBD vaccine, with a long-lasting high level of IgG antibodies and neutralizing antibodies induced by RBDdelta-Fc vaccine. This RBDdelta-Fc vaccine, as well as the RBD-Fc vaccine prepared in our previously study, could trigger a durable immune effect by the heterologous boosting immunity, and the RBD-Fc induced a quicker humoral immune response than the homologous immunization with inactivated vaccines. In conclusion, the Fc fusion strategy has a significant role in enhancing the immunogenicity of recombinant protein vaccines, thus promising the development of a safe and efficient vaccine for the heterologous boosting against SARS-CoV-2.

Anciently duplicated genes continuously recruited to heart expression in vertebrate evolution are associated with heart chamber increase.

Although gene/genome duplications in the early stage of vertebrates have been thought to provide major resources of raw genetic materials for evolutionary innovations, it is unclear whether they continuously contribute to the evolution of morphological complexity during the course of vertebrate evolution, such as the evolution from two heart chambers (fishes) to four heart chambers (mammals and birds). We addressed this issue by our heart RNA-Seq experiments combined with published data, using 13 vertebrates and one invertebrate (sea squirt, as an outgroup). Our evolutionary transcriptome analysis showed that number of ancient paralogous genes expressed in heart tends to increase with the increase of heart chamber number along the vertebrate phylogeny, in spite that most of them were duplicated at the time near to the origin of vertebrates or even more ancient. Moreover, those paralogs expressed in heart exert considerably different functions from heart-expressed singletons: the former are functionally enriched in cardiac muscle and muscle contraction-related categories, whereas the latter play more basic functions of energy generation like aerobic respiration. These findings together support the notion that recruiting anciently paralogous genes that are expressed in heart is associated with the increase of chamber number in vertebrate evolution.

Rational Identification of Novel Antibody-Drug Conjugate with High Bystander Killing Effect against Heterogeneous Tumors.

Bystander-killing payloads can significantly overcome the tumor heterogeneity issue and enhance the clinical potential of antibody-drug conjugates (ADC), but the rational design and identification of effective bystander warheads constrain the broader implementation of this strategy. Here, graph attention networks (GAT) are constructed for a rational bystander killing scoring model and ADC construction workflow for the first time. To generate efficient bystander-killing payloads, this model is utilized for score-directed exatecan derivatives design. Among them, Ed9, the most potent payload with satisfactory permeability and bioactivity, is further used to construct ADC. Through linker optimization and conjugation, novel ADCs are constructed that perform excellent anti-tumor efficacy and bystander-killing effect in vivo and in vitro. The optimal conjugate T-VEd9 exhibited therapeutic efficacy superior to DS-8201 against heterogeneous tumors. These results demonstrate that the effective scoring approach can pave the way for the discovery of novel ADC with promising bystander payloads to combat tumor heterogeneity.

Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.

Transfer of massive mitochondria from astrocytes reduce propofol neurotoxicity.

Studies have shown that propofol-induced neurotoxicity is mediated by disruption of mitochondrial fission and fusion, leading to an imbalance in energy supply for developing neurons. Healthy mitochondria released from astrocytes migrate to compromised neurons to mitigate propofol-induced neurotoxicity, yet the precise mechanisms involved require further clarification. In our investigation, primary neurons were incubated with propofol, which decreased ATP synthesis and mitochondrial membrane potential, increased ROS generation and neuronal apoptosis. Notably, astrocytes did not respond to the deleterious effects of propofol. The culture medium of neurons or astrocytes incubated with propofol was collected. It was found that mitochondrial ratio was decreased and mitochondrial function was impaired. Non-contact co-culture of neuro-astrocytes facilitated transcellular mitochondrial transfer in both physiological and propofol interventions, but failed to reverse propofol-induced neurotoxicity. The more pronounced damage to neuronal mitochondria induced by propofol compared to that in astrocytes alludes to secondary injury. Damaged neurons incubated with large, functional extracellular mitochondria derived from astrocytes demonstrates transfer of mitochondria to neurons, effectively reversing propofol-induced neurotoxicity. This discovery presents a novel mitochondrial transfer of neuro-astrocytes crosstalk that contributes to neuroprotection and neurological recovery in neurotoxicity.

Stem cell landscape aids in tumor microenvironment identification and selection of therapeutic agents in gastric cancer.

Gastric cancer stem cells (GCSCs) are strongly associated with the refractory characteristics of gastric cancer, including drug resistance, recurrence, and metastasis. The prognosis for advanced gastric cancer patients treated with multimodal therapy after surgery remains discouraging. GCSCs hold promise as therapeutic targets for GC patients. We obtained 26 sets of stem cell-related genes from the StemChecker database. The Consensus clustering algorithm was employed to discern three distinct stemness subtypes. Prognostic outcomes, components of the tumor microenvironment (TME), and responses to therapies were compared among these subtypes. Following this, a stemness-risk model was formulated using weighted gene correlation network analysis (WGCNA), alongside Cox regression and random survival forest analyses. The C2 subtype predominantly showed enrichment in negative prognostic CSC gene sets and demonstrated an immunosuppressive TME. This specific subtype exhibited minimal responsiveness to immunotherapies and demonstrated reduced sensitivity to drugs. Four pivotal genes were integrated into the construction of the stemness model. Gastric cancer patients with higher stemness-risk scores demonstrated poorer prognoses, a greater presence of immunosuppressive components in TME, and lower rates of treatment response. Subset analysis indicated that only the low-stemness risk subtype derives benefit from 5-fluorouracil-based adjuvant chemotherapy. The model's effectiveness in immunotherapeutic prediction was further validated in the PRJEB25780 cohort. Our study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of TME infiltration, and varying sensitivity or resistance to standard chemotherapy or targeted therapy. We propose that the stemness risk model may help the development of well-grounded treatment recommendations and prognostic assessments.

The effects of art therapy on quality of life and psychosomatic symptoms in adults with cancer: a systematic review and meta-analysis.

BACKGROUND: Cancer-related psychological and physical disorders can mean stressful and painful experiences for patients. Art therapy, a form of complementary and alternative medicine, is an increasingly popular way to decrease emotional stress, alleviate somatic symptoms, and improve quality of life in patients with cancer. However, current systematic reviews have not explored the beneficial effects of art therapy. Moreover, there have been inconsistent findings on the effect of this therapy, and there is insufficient evidence to confirm the effects in adults with cancer. The objective of this study was to determine the efficacy of art therapy in improving quality of life and psychosomatic symptoms in adults with cancer. METHODS: This systematic review and meta-analysis included adults with all kinds of cancer. Six English-language and three large Chinese-language databases were comprehensively searched for relevant studies. Gray literature and references were also checked. The quality of the included studies was evaluated using the Cochrane risk-of-bias assessment tool. RESULTS: Eight eligible randomized controlled trials conducted in four countries were included. Art therapy improved overall quality of life, but had no significant effect on psychological health or physical health sub-dimensions in women with cancer. Moreover, art therapy alleviated anxiety and depression, but had only a tendency toward an effect on somatic symptoms. CONCLUSIONS: Moderate-quality evidence shows that art therapy is beneficial for women with cancer in terms of improving the overall quality of life and alleviating emotional symptoms (anxiety and depression). However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms.

Methylation of hypoxia-inducible factor 3 subunit alpha contributes to poor prognosis in lung adenocarcinoma.

Hypoxia-inducible factor 3 subunit alpha (HIF3A) has been implicated in various types of cancers, while its precise role in the lung adenocarcinoma remains unclear. Our study aimed to investigate the roles of HIF3A in lung adenocarcinoma and its regulation by DNA methylation. We utilized bioinformatic tools, including UALCAN and KMPlot, to analyze the relationship between HIF3A expression, DNA methylation, and patient survival rate in lung adenocarcinoma. We also used siRNA-mediated knockdown of HIF3A and DNA-methyltransferase 1 (DNMT1), as well as the treatment of DNA methylation inhibitor 5-Azacytidine, in A549 and H1299 lung adenocarcinoma cell lines. qPCR, MTT, and cell counting assays were performed to evaluate the mRNA expression and cell viability. The bioinformatic analysis revealed that HIF3A expression was downregulated and its methylation was upregulated in lung tumor tissues. Additionally, Kaplan-Meier analysis indicated a correlation between low HIF3A expression and patient poor survival rate. We found that DNMT1 regulated HIF3A methylation. Knockdown of HIF3A promoted cancer cell proliferation. These data suggest that downregulation of HIF3A promotes tumor cell proliferation, and support that HIF3A methylation may serve as a prognostic factor for lung adenocarcinoma.

Catalyzing Generation and Stabilization of Oxygen Vacancies on CeO2-x Nanorods by Pt Nanoclusters as Nanozymes for Catalytic Therapy.

Although CeO2 nanomaterials have been widely explored as nanozymes for catalytic therapy, they still suffer from relatively low activities. Herein, the catalyzing generation and stabilization of oxygen vacancies on CeO2 nanorods by Pt nanoclusters via H2 gas reduction under mild temperature (350 °C) to obtain Pt/CeO2- x , which can serve as a highly efficient nanozyme for catalytic cancer therapy, is reported. The deposited Pt on CeO2 by the atomic layer deposition technique not only can serve as the catalyst to generate oxygen vacancies under mild temperature reduction through the hydrogen spillover effect, but also can stabilize the generated oxygen vacancies. Meanwhile, the oxygen vacancies also provide anchoring sites for Pt forming strong metal-support interactions and thus preventing their agglomerations. Importantly, the Pt/CeO2- x reduced at 350 °C (Pt/CeO2- x -350R) exhibits excellent enzyme-mimicking catalytic activity for generation of reactive oxygen species (e.g., ·OH) as compared to other control samples, including CeO2 , Pt/CeO2 , and Pt/CeO2- x reduced at other temperatures, thus achieving excellent performance for tumor-specific catalytic therapy to efficiently eliminate cancer cells in vitro and ablate tumors in vivo. The excellent enzyme-mimicking catalytic activity of Pt/CeO2- x -350R originates from the good catalytic activities of oxygen vacancy-rich CeO2- x and Pt nanoclusters.