Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice

Receptor-interacting protein kinase 3 (Ripk3) is one of the critical mediators of inflammatory cytokine-stimulated signaling. Here we show that Ripk3 signaling selectively regulates both the number and the function of hematopoietic stem cells (HSCs) during stress conditions. Ripk3 signaling is not required for normal homeostatic hematopoiesis. However, in response to serial transplantation, inactivation of Ripk3 signaling prevents stress-induced HSC exhaustion and functional HSC attenuation, while in response to fractionated low doses of ionizing radiation (IR), inactivation of Ripk3 signaling accelerates leukemia/lymphoma development. In both situations, Ripk3 signaling is primarily stimulated by tumor necrosis factor-α. Activated Ripk3 signaling promotes the elimination of HSCs during serial transplantation and pre-leukemia stem cells (pre-LSCs) during fractionated IR by inducing Mlkl-dependent necroptosis. Activated Ripk3 signaling also attenuates HSC functioning and represses a pre-LSC-to-LSC transformation by promoting Mlkl-independent senescence. Furthermore, we demonstrate that Ripk3 signaling induces senescence in HSCs and pre-LSCs by attenuating ISR-mediated mitochondrial quality control

Water-Soluble pillararene-functionalized graphene oxide for in vitro raman and fluorescence dual-mode imaging

This study provides a successful preparation of biocompatible hybrid materials (1-GO and 2-GO) by the integration of graphene oxide (GO) with water-soluble pillararenes (bolaamphiphile 1 and tadpolelike amphiphile 2) for dual-mode Raman and fluorescence bioimaging in vitro. The investigations show that pillararenes 1 and 2 were loaded onto the surface of GO through strong hydrogen-bonding interactions. Aqueous suspensions of 1-GO and 2-GO are stable and can be kept for a long time. After confirming their good biocompatibility by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the 1-GO and 2-GO hybrids were endocytosed by HeLa cells for in vitro Raman imaging. It was found that 1-GO presents better Raman imaging than 2-GO. When a fluorescent guest molecule, bipyridinium derivative 3, was added into the suspensions of the hybrids, the suspensions of 1-GO and 2-GO were as stable as the original. The suspensions of the inclusion complexes (1-GO[DOT OPERATOR]3 and 2-GO[DOT OPERATOR]3) formed from 1-GO and 2-GO with 3 can also be endocytosed by HeLa cells to enable in vitro fluorescence imaging to be performed. It was found that 1-GO[DOT OPERATOR]3 performs better than 2-GO[DOT OPERATOR]3. The current research has determined the capacities of pillararene-modified GO for combined bioimaging, which paves the way for using these biocompatible materials towards dual-mode diagnostics

Biocompatible Pillararene-Assembly-Based Carriers for Dual Bioimaging

Present research provides a successful example to use biocompatible pillararene-based assemblies for delivering mixed dyes in dual bioimaging. A series of tadpole-like and bola amphiphilic pillararenes <b>1</b>–<b>4</b> were synthesized by selectively employing water-soluble ethylene glycols and hydrophobic alkyl units as the starting materials. In comparison with their monomers, these amphiphilic pillararenes not only show improved biocompatibility to cells but also could form homogeneous supramolecular self-assemblies. Interestingly, different types of amphiphilic pillararene-based assemblies exhibit various performances on the delivery of dyes with different aqueous solubility. All assemblies can deliver water-soluble rhodamine B to cells, while only tadpole-like amphiphilic pillararene-based assemblies performed better on delivering hydrophobic fluorescein isothiocyanate for imaging. In addition, pillararene derivatives <b>1</b>, <b>3</b>, and <b>4</b> could complex with a viologen guest, further forming stable assemblies for bioimaging. In such cases, the assembly formed from the complex of tadpole-like amphiphile pillararene <b>1</b> with the viologen guest performed better in delivering mixed dyes. Finally, an anticancer drug, doxorubicin, was successfully delivered to cells by using the pillararene-based assemblies. The current research has determined the capacities of pillararene-based assemblies to deliver different dyes for bioimaging and paves the way for using these biocompatible carriers toward combined cancer therapy

Unimolecular photoconversion of multicolor luminescence on hierarchical self-assemblies

Facile tuning of photophysical properties is highly desirable for boosting the performance and versatility of photoluminescent materials. In an attempt to overcome the challenge of achieving the photoswitching of multicolor luminescence on unimolecular platforms, we here report a novel hierarchical self-assembly of a cyanostilbene–naphthalimide dyad as the realization of phototunable luminescence at the unimolecular level. The work takes advantage of the photoisomerization of the cyanostilbene moiety from the Z form to its E form, which causes a morphological disorder in the molecular self-assembly and gives rise to a dual fluorescent characteristic accompanied by a progressive luminescent color conversion from yellow to green and finally to blue. Such systems with convertible multicolor luminescence might exhibit application potentials for unimolecular selective imaging and labeling, as exemplified by the cell imaging studies presented in this work

Thermo-responsive fluorescent vesicles assembled by fluorescein-functionalized pillar[5]arene

Fluorescent vesicles were successfully prepared through the self-assembly of a fluorescein-functionalized pillar[5]arene. The vesicular superstructure exhibits thermo-responsive emission under variable temperatures

Covalent Organic Frameworks Formed with Two Types of Covalent Bonds Based on Orthogonal Reactions

Covalent organic frameworks (COFs) are excellent candidates for various applications. So far, successful methods for the constructions of COFs have been limited to a few condensation reactions based on only one type of covalent bond formation. Thus, the exploration of a new judicious synthetic strategy is a crucial and emergent task for the development of this promising class of porous materials. Here, we report a new orthogonal reaction strategy to construct COFs by reversible formations of two types of covalent bonds. The obtained COFs consisting of multiple components show high surface area and high H₂ adsorption capacity. The strategy is a general protocol applicable to construct not only binary COFs but also more complicated systems in which employing regular synthetic methods did not work

Biocompatible pillararene-assembly-based carriers for dual bioimaging

Present research provides a successful example to use biocompatible pillararene-based assemblies for delivering mixed dyes in dual bioimaging. A series of tadpole-like and bola amphiphilic pillararenes 1–4 were synthesized by selectively employing water-soluble ethylene glycols and hydrophobic alkyl units as the starting materials. In comparison with their monomers, these amphiphilic pillararenes not only show improved biocompatibility to cells but also could form homogeneous supramolecular self-assemblies. Interestingly, different types of amphiphilic pillararene-based assemblies exhibit various performances on the delivery of dyes with different aqueous solubility. All assemblies can deliver water-soluble rhodamine B to cells, while only tadpole-like amphiphilic pillararene-based assemblies performed better on delivering hydrophobic fluorescein isothiocyanate for imaging. In addition, pillararene derivatives 1, 3, and 4 could complex with a viologen guest, further forming stable assemblies for bioimaging. In such cases, the assembly formed from the complex of tadpole-like amphiphile pillararene 1 with the viologen guest performed better in delivering mixed dyes. Finally, an anticancer drug, doxorubicin, was successfully delivered to cells by using the pillararene-based assemblies. The current research has determined the capacities of pillararene-based assemblies to deliver different dyes for bioimaging and paves the way for using these biocompatible carriers toward combined cancer therapy