Redox-active species in ambient particulate matter (PM) cause adverse health effects through the production of reactive oxygen species (ROS) in the human respiratory tract. However, respiratory deposition of these species and their relative contributions to oxidative potential (OP) have not been described. Size-segregated aerosols were collected during haze and nonhaze periods using a micro-orifice uniform deposit impactor sampler at an urban site in Shanghai to address this issue. Samples were analyzed for redox-active species content and PM OP. The average dithiothreitol (DTT) activity of haze samples was approximately 2.4-fold higher than that of nonhaze samples and significantly correlated with quinone and water-soluble metal concentrations. The size-specific distribution data revealed that both water-soluble OP (volume-normalized OP quantified by DTT assay) and OP (mass-normalized OP) were unimodal, peaking at 0.56-1 and 0.1-0.32 μm, respectively, due to contributions from accumulation-mode quinones and water-soluble metals. We further estimated that transition metals (mainly copper and manganese) contributed 55 ± 13% of the DTT activity while quinones accounted for only 8 ± 3%. Multiple-path particle dosimetry calculations estimated that OP deposition in the pulmonary region was mainly from accumulation-mode transition metals despite quinones having the highest DTT activity. This behavior is primarily attributed to the efficiency of deposition of transition metals in the pulmonary region being approximately 1.2-fold greater than that of quinones. These results reveal that accumulation-mode transition metals are significant contributors to the OP of deposited water-soluble particles in the pulmonary region of the lung.

Two structurally different polymorphs of cobalt(II) imidazolate frameworks are solvothermally synthesized by using N,N-dimethylacetamide as a template: The polymorph 6 (a = 9.797 (4) angstroms, b = 15.301(6) angstroms, c =14.902(6) angstroms, beta = 98.904(6) degrees, monoclinic, P21/n) shows structures of silicate CaAl2Si2O8 with CrB4 topology, while polymorph 7 (a = 15.173(4) angstroms, b = 15.173(4) angstroms, c = 19.089(5) angstroms, Pbca) shows CaGa2O4-related topological structures. In addition, the 7' (a = 15.9712(18) angstroms, b = 15.9253(19) angstroms, c = 18.475(2) angstroms, Pbca), a compound isostructural with 7, is synthesized by using cyclohexanol as a template. Thus, these cobalt(II) imidazolate polymers are reminiscent of the zeolite syntheses in that not only the same topological structure can be synthesized by using the different organic templates, but also different topological structures can be synthesized by using the same organic template.

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Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system transformation in MLL-rearranged (MLL-r) leukemia. Of these genes, HOXA9 has been shown to be critical for leukemia cell survival, while MEIS1 has been identified as an essential regulator for leukemia stem cell (LSC) maintenance. Although significantly high expression of PBX3 was observed in clinical acute myeloid leukemia (AML) samples, the individual role of PBX3 in leukemia development is still largely unknown. In this study, we explored the specific role of PBX3 and its associated regulatory network in leukemia progression. By analyzing the clinical database, we found that the high expression of PBX3 is significantly correlated with a poor prognosis in AML patients. ChIP-Seq/qPCR analysis in MLL-r mouse models revealed aberrant epigenetic modifications with increased H3K79me2, and decreased H3K9me3 and H3K27me3 levels in LSCs, which may account for the high expression levels of Pbx3. To further examine the role of Pbx3 in AML maintenance and progression, we used the CRISPR/Cas9 system to delete Pbx3 in leukemic cells in the MLL-AF9 induced AML mouse model. We found that Pbx3 deletion significantly prolonged the survival of leukemic mice and decreased the leukemia burden by decreasing the capacity of LSCs and promoting LSC apoptosis. In conclusion, we found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia.

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Development of nanoplatforms that can amplify the passive tumor targeting effect based on enhanced permeability and retention (EPR) effect is crucial for precision cancer nanomedicine applications. Herein, we present the development of core−shell tecto dendrimers (CSTDs) as a platform for enhanced tumor magnetic resonance (MR) imaging through an amplified EPR effect. In this work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were decorated with β-cyclodextrin (CD) and then assembled with G3 PAMAM dendrimers premodified with adamantane (Ad) via supramolecular recognition of CD and Ad. The formed G5-CD/Ad-G3 CSTDs were conjugated with tetraazacyclododecane tetraacetic acid (DOTA)-Gd(III) chelators and further acetylated to neutralize the remaining CSTD periphery amines. We reveal that the formed CSTD.NHAc-DOTA(Gd) (CSTD-D-Gd) complexes have a narrow size distribution and satisfactory colloidal stability, and are cytocompatible within the concentration range studied. Compared to the single dendrimer counterpart of G5.NHAc-DOTA(Gd) (G5-D-Gd) complexes, the CSTD-D-Gd complexes with a higher molecular weight and volume possess a longer rotation correlation time, hence having a longitudinal relaxivity (r 1 ) of 7.34 mM −1 s −1 , which is 1.5 times larger than that of G5-D-Gd complexes (4.92 mM −1 s −1 ). More importantly, the CSTD-D-Gd complexes display better permeability in the three-dimensional (3D) cell spheroids in vitro through fluorescence imaging and a more significant EPR effect for improved tumor MR imaging in vivo than the G5-DOTA-Gd complexes. The generated CSTD-D-Gd complexes may be adopted for enhanced tumor MR imaging through an amplified passive EPR effect and also be further extended for different cancer theranostic applications.