Next-generation high-performance structural materials are required for lightweight design strategies and advanced energy applications. Maraging steels, combining a martensite matrix with nanoprecipitates, are a class of high-strength materials with the potential for matching these demands. Their outstanding strength originates from semi-coherent precipitates, which unavoidably exhibit a heterogeneous distribution that creates large coherency strains, which in turn may promote crack initiation under load. Here we report a counterintuitive strategy for the design of ultrastrong steel alloys by high-density nanoprecipitation with minimal lattice misfit. We found that these highly dispersed, fully coherent precipitates (that is, the crystal lattice of the precipitates is almost the same as that of the surrounding matrix), showing very low lattice misfit with the matrix and high anti-phase boundary energy, strengthen alloys without sacrificing ductility. Such low lattice misfit (0.03 ± 0.04 per cent) decreases the nucleation barrier for precipitation, thus enabling and stabilizing nanoprecipitates with an extremely high number density (more than 10 per cubic metre) and small size (about 2.7 ± 0.2 nanometres). The minimized elastic misfit strain around the particles does not contribute much to the dislocation interaction, which is typically needed for strength increase. Instead, our strengthening mechanism exploits the chemical ordering effect that creates backstresses (the forces opposing deformation) when precipitates are cut by dislocations. We create a class of steels, strengthened by Ni(Al,Fe) precipitates, with a strength of up to 2.2 gigapascals and good ductility (about 8.2 per cent). The chemical composition of the precipitates enables a substantial reduction in cost compared to conventional maraging steels owing to the replacement of the essential but high-cost alloying elements cobalt and titanium with inexpensive and lightweight aluminium. Strengthening of this class of steel alloy is based on minimal lattice misfit to achieve maximal precipitate dispersion and high cutting stress (the stress required for dislocations to cut through coherent precipitates and thus produce plastic deformation), and we envisage that this lattice misfit design concept may be applied to many other metallic alloys.

The myocardium responds to chronic pressure or volume overload by activation and proliferation of cardiac fibroblasts and their differentiation into myofibroblasts. Because alpha-smooth muscle actin (SMA) expression is the classical marker for myofibroblast differentiation, we examined force-induced SMA expression and regulation by specific MAPK pathways. Rat cardiac fibroblasts were separated from myocytes and smooth muscle cells, cultured, and phenotyped by using the presence of SMA, vimentin, and ED-A fibronectin and the absence of desmin as myofibroblast markers. Static tensile forces (0.65 pN/microm2) were applied to fibroblasts via collagen-coated magnetite beads. In neonatal cardiac fibroblasts cultured for 1 day, immunostaining and Western and Northern blotting showed very low basal levels of SMA. After the application of force, there were 1.5- to 2-fold increases of SMA protein and mRNA within 4 h. Force-induced SMA expression was dependent on ERK phosphorylation and on intact actin filaments. In contrast to cells cultured for 1 day, cells grown for 3 days on rigid substrates showed prominent stress fibers and high basal levels of SMA, which were reduced by 32% within 4 h after force application. ERK was not activated by force, but p38 phosphorylation was required for force-induced inhibition of SMA expression. These results indicate that mechanical force-induced regulation of SMA content is dependent on myofibroblast differentiation and by selective activation of MAPKs.

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.

mTOR (mammalian target of rapamycin) signaling plays a key role in the development of many tumor types. Therefore, mTOR is an attractive target for cancer therapeutics. Although mTOR inhibitors are thought to have radiosensitization activity, the molecular bases remain largely unknown. Here we show that treating MCF7 breast cancer cells with rapamycin (an mTOR inhibitor) results in significant suppression of homologous recombination (HR) and nonhomologous end joining (NHEJ), two major mechanisms required for repairing ionizing radiation-induced DNA DSBs. We observed that rapamycin impaired recruitment of BRCA1 and Rad51 to DNA repair foci, both essential for HR. Moreover, consistent with the suppressive role of rapamycin on both HR and NHEJ, persistent radiation-induced DSBs were detected in cells pretreated with rapamycin. Furthermore, the frequency of chromosome and chromatid breaks was increased in cells treated with rapamycin before and after irradiation. Thus our results show that radiosensitization by mTOR inhibitors occurs via disruption of the major two DNA DSB repair pathways.