Ionizing radiation (IR) has been extensively used in industry and radiotherapy, but IR exposure from nuclear or radiological accidents often causes serious health effects in an exposed individual, and its application in radiotherapy inevitably brings undesirable damage to normal tissues. In this work, we have developed ultrathin twodimensional (2D) niobium carbide (Nb 2 C) MXene as a radioprotectant and explored its application in scavenging free radicals against IR. The 2D Nb 2 C MXene features intriguing antioxidant properties in effectively eliminating hydrogen peroxide (H 2 O 2 ), hydroxyl radicals ( • OH), and superoxide radicals (O 2•− ). Pretreatment with biocompatible polyvinylpyrrolidone (PVP)-functionalized Nb 2 C nanosheets (Nb 2 C-PVP NSs) significantly reduces IR-induced production of reactive oxygen species (ROS), resulting in enhanced cell viability in vitro. A single intravenous injection of Nb 2 C-PVP significantly enhances the survival rate of 5 and 6.5 Gy irradiated mice to 100% and 81.25%, respectively, and significantly increases bone marrow mononuclear cells after IR. Critically, Nb 2 C-PVP reverses the damage of the hematopoietic system in irradiated mice. Single administration of Nb 2 C-PVP significantly increases superoxide dismutase (SOD) activities, decreases malondialdehyde levels, and thereby reduces IR-induced pathological damage in the testis, small intestine, lung, and liver of 5 Gy irradiated mice. Importantly, Nb 2 C-PVP is almost completely eliminated from the mouse body on day 14 post treatment, and no obvious toxicities are observed during the 30-day post treatment period. Our study pioneers the application of 2D MXenes with intrinsic radioprotective nature in vivo.

A series of poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) homopolymers and poly(2-(dimethylamino)ethyl methacrylate)-b-poly(acrylic acid) (PDMAEMA-b-PAA) diblock copolymers were synthesized by atomic transfer radical polymerization. Thanks to a fine-tuning of the hydrophobic-hydrophilic balance by varying the molecular weight of the polymers and the pH of the aqueous solutions, as well as the composition for the block copolymers, the lower critical solution temperature (LCST) and the aggregation-dissolution kinetics of PDMAEMA homopolymers and PDMAEMA-b-PAA block copolymers can be adjusted. For the block copolymers, the results show that larger relative size of the PDMAEMA blocks leads to an increasing tendency to form micellar aggregates and a decrease of the LCST of the aqueous solution, which is consistent with the increasing copolymer hydrophobicity. A significant difference of the stimuli-responsive behavior between PDMAEMA-rich and PAA-rich copolymers is observed, because the former exhibit thermo-responsive behavior in a broad temperature range of 40-60 °C in basic media, while the pH-responsive behavior is dominant, and only a weak thermo-responsive behavior is exhibited around the specific isoelectric point (IEP) in the latter case. The aggregation rate is strongly influenced by temperature, molecular weight, structure, and composition of the polymer. Specifically, temperature has a stronger effect than the molar ratio of the PDMAEMA segment in the copolymer (related to its hydrophobicity) and the chain molecular weight, although the PDMAEMA-b-PAA copolymers show faster aggregation rate than do the PDMAEMA homopolymers.

Cytosolic Ca2+ ([Ca2+]i) plays an important role in endothelial cell signaling. Although it has been suggested that the influx of Ca2+ can be triggered by depletion of intracellular Ca2+ stores, the mechanism (or mechanisms) underlying this phenomenon needs further elaboration. In the present study, involvement of myosin light-chain kinase (MLCK) in the regulation of Ca2+ signaling was investigated in agonist- and fluid flow-stimulated endothelial cells loaded with Ca2+-sensitive dyes. Bradykinin (BK) and thapsigargin caused an increase in [Ca2+]i followed by a sustained rise due to Ca2+ influx from extracellular space and shifted total myosin light-chain (MLC) from the unphosphorylated to the diphosphorylated form. ML-9 (100 microM), an inhibitor of MLCK, abolished Ca2+ influx and prevented MLC diphosphorylation in BK- and thapsigargin-treated cells, but did not affect Ca2+ mobilization from internal stores. Fluid flow stimulation (shear stress=5 dynes/cm2) increased [Ca2+]i and enhanced MLC phosphorylation. ML-9 also inhibited Ca2+ response and MLC phosphorylation in fluid flow-stimulated cells. The Ca2+ influx in response to BK was linearly correlated with the diphosphorylation of MLC in ML-9 treated cells. Effects of ML-5 and ML-7, analogs of ML-9, to inhibit Ca2+ influx paralleled their potencies to inhibit MLCK activity. These findings demonstrate that MLCK plays an essential role in regulating the plasmalemmal Ca2+ influx in agonist- and fluid flow-stimulated endothelial cells. This study is the first to report the close relationship between Ca2+ influx and MLC diphosphorylation.

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