The single‐atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese‐based SAE (Mn/PSAE) by coordination of single‐atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H2O2 to .OH through a Fenton‐like reaction; it also promotes the decomposition of H2O2 to O2 and continuously catalyzes the conversion of O2 to cytotoxic .O2− via oxidase‐like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

The targeted delivery of chemotherapeutic drugs is amajor challenge in the clinical treatment of cancer.Herein, we constructed amultifunctional DNAnanoplatform as aversatile carrier of the highly potent platinum-based DNAintercalator, 56MESS.I no ur rational design, 56MESS was efficiently loaded into the double-bundle DNAt etrahedron through intercalation with the DNAd uplex. With the integration of an anobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNAn anocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapyw ithout obvious systemic toxicity. This DNA-based platinum-drug delivery system provides apromising strategy for the treatment of tumors.

Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

to perform PDT. [7] PSs absorb laser energy in the presence of O 2 to produce cytotoxic reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) that causes the destruction of the genetic material in cancer cells, leading to cell apoptosis, or necrosis. [7][8][9][10] The O 2 involved in PDT improves tumor destruction and reduces the toxic side effects as compared with other conventional therapeutic modalities like radiotherapy, chemotherapy, and surgery. [11][12][13][14][15] However, hypoxia, one of the hallmarks of malignant tumors, [16][17][18] induces an unexpected resistance of tumors to PDT, since molecular O 2 plays an essential role during the process. Some types of nanocatalysts have been used to address this dilemma, such as manganese dioxide (MnO 2 ) nanoparticles, carbon dot, and single-atom ruthenium (Ru) for an in situ catalysis of the decomposition of H 2 O 2 to generate O 2 . [6,14,19] This could be an effective strategy to relieve hypoxia in the tumor microenvironment (TME), thus becoming a potential approach to improve the efficacy of PDT. [20] Additionally, the acidic TME with an excessive amount of H 2 O 2 is a natural activator of these nanocatalysts, making them intelligent nanocatalysts for tumor specific therapy. [21][22][23] Recently, MnO 2 nanostructures have received extensive attention in the field of bio-applications for their efficient O 2 production and easy synthesis, [24][25][26][27] enhancing the effect of radiation therapy, [27] chemotherapy, [28] and PDT. [29] In addition, MnO 2 is rapidly decomposed into water soluble Mn 2+ ion in an acidic condition, [6,[30][31][32][33][34] and excreted through the bile into the feces, avoiding unexpected accumulation and long-term toxicity in vivo. [6,29] However, MnO 2 nanostructures without surface coating have a poor structure stability under physiological conditions, [35] and it is difficult to control their size and morphology during the synthesis, thus, increasing the uncertainty of the reactivity of the nanomaterial. [25] Therefore, it is highly desirable to construct MnO 2 nanoparticles with uniform morphology, high stability and biocompatibility for biomedical applications.Ferritin (Ftn) is an endogenous iron storage protein composed of 24 subunits, with a hollow structure of 12 nm in the external diameter and an inner cavity of 8 nm. [36] Ftn has been widely used as a superior protein nanocage for the Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O 2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO 2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/ Ftn@MnO 2 ) for tumor therapy. Ce6/Ftn@MnO 2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis dem...

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LHPs are emerging as highly efficient light emitters with a narrow full width at half-maximum (FWHM) and tunable emission throughout the visible region (400-700 nm). [3] In particular, all inorganic cesium lead halide (CsPbX 3 , X = Cl, Br, I) perovskite quantum dots (QDs) with near-unity photoluminescence quantum yields (PLQYs) in the blue, green, and red regions and high color purity have been regarded as highly efficient narrow-band phosphors for lighting and next-generation displays devices. [4] Despite their excellent optical properties together with their impressive performance in various lighting fields, LHPs have received criticism because of the toxicity of lead and the lack of long-term stability. [5] Concerning the environmental issues, tin-, bismuth-, and antimony-based analogs such as CsSnX 3 , [6] Cs 3 Bi 2 X 9 , [7] and Cs 3 Sb 2 X 9 , [8] were developed to replace the toxic lead complexes, but both the PLQYs and the stability failed to meet the requirements of practical applications. For example, CsSnX 3 suffers from a low PLQY (0.14% for CsSnBr 3 QDs); simultaneously, it is highly sensitive to oxygen, which subsequently results in severe photoluminescence (PL) quenching. [6] Recently, silverbismuth-based Cs 2 AgBiX 6 double perovskites have attracted wide attention owing to their relatively higher stability. [5a,9] Nevertheless, the PLQY (6.7% for Cs 2 AgBiCl 6 QDs) is still limited. [9a] Similarly, tin(IV)-based Cs 2 SnX 6 double perovskites Lead halide perovskites (LHPs) have received increased attention owing to their intriguing optoelectronic and photonic properties. However, the toxicity of lead and the lack of long-term stability are potential obstacles for the application of LHPs. Herein, the epitaxial synthesis of CsPbX 3 (X = Cl, Br, I) perovskite quantum dots (QDs) by surface chemical conversion of Cs 2 GeF 6 double perovskites with PbX 2 (X = Cl, Br, I) is reported. The experimental results show that the surface of the Cs

Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg −1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3′-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy.

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidaselike activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H 2 O 2 and then efficiently activate H 2 O 2 to produce • OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.