The mechanism of tumor necrosis factor (TNF)-induced nonapoptotic cell death is largely unknown, although the mechanism of TNF-induced apoptosis has been studied extensively. In wild-type mouse embryonic fibroblast cells under a caspase-inhibited condition, TNF effectively induced cell death that morphologically resembled necrosis. In this study, we utilized gene knockout mouse embryonic fibroblasts cells and found that tumor necrosis factor receptor (TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF-induced necrotic cell death. Inhibitors of NF-B facilitated TNF-induced necrotic cell death, suggesting that NF-B suppresses the necrotic cell death pathway. JNK, p38, and ERK activation seem not to be required for this type of cell death because mitogen-activated protein kinase inhibitors did not significantly affect TNF-induced necrotic cell death. In agreement with the previous reports that the reactive oxygen species (ROS) may play an important role in this type of cell death, the ROS scavenger butylated hydroxyanisole efficiently blocked TNF-induced necrotic cell death. Interestingly, during TNF-induced necrotic cell death, the cellular ROS level was significantly elevated in wild type, but not in RIP ؊/؊ , TRAF2 ؊/؊ , and FADD ؊/؊ cells. These results suggest that RIP, TRAF2, and FADD are crucial in mediating ROS accumulation in TNF-induced necrotic cell death.

Carbon dots (CDs) have various attractive properties and potential applications, but there is much less attention paid to their phosphorescent phenomenon and mechanism. Herein, we prepared a kind of highly efficient CD-based phosphorescent material by a subtle design method that incorporated N-doped CDs (NCDs) into composite matrices (the melting recrystallization urea and biuret from the heating urea) by a one-pot heating treatment for the mixture of urea and NCDs. Through systematic investigation, CN bonds on the surface of the NCDs can create new energy level structures, and for the first time, evidence that shows they are the origin of phosphorescence is presented. Composite matrices play a dual role to suppress the vibrational dissipation of long-lived triplets by combining the rigidity of the melting recrystallization urea and hydrogen bonding between biuret and NCDs, which have obvious advantages over a single-component matrix. The results show the obtained materials have an ultralong phosphorescent lifetime of 1.06 s under 280 nm excitation and a high phosphorescent quantum yield of 7% under 360 nm excitation in air, which are the highest values recorded for the CDbased materials. These CD-based room-temperature phosphorescent materials have also shown potential in white light-emitting diodes and data security.

Phosphorescence shows great potential for application in bioimaging and ion detection because of its long-lived luminescence and high signal-to-noise ratio, but establishing phosphorescence emission in aqueous environments remains a challenge. Herein, we present a general design strategy that effectively promotes phosphorescence by utilising water molecules to construct hydrogen-bonded networks between carbon dots (CDs) and cyanuric acid (CA). Interestingly, water molecules not only cause no phosphorescence quenching but also greatly enhance the phosphorescence emission. This enhancement behaviour can be explained by the fact that the highly ordered bound water on the CA particle surface can construct robust bridge-like hydrogen-bonded networks between the CDs and CA, which not only effectively rigidifies the C=O bonds of the CDs but also greatly enhances the rigidity of the entire system. In addition, the CD-CA suspension exhibits a high phosphorescence lifetime (687 ms) and is successfully applied in ion detection based on its visible phosphorescence.

The transcription factor NF-B is activated when cells are exposed to genotoxic stress. It has been suggested that DNA damage will trigger a cytoplasmic signaling that leads to the activation of IKK and NF-B, but the signaling components upstream of IKK have not yet been identified. Here we report that the receptor interacting protein, RIP, is the IKK upstream component, essential for the activation of NF-B by DNA damage. Also, our findings suggest that this NF-B activation by DNA damage is not mediated by autocrine or TNF-R1 signaling pathway. In wild-type fibroblasts, DNA damage induced by agents such as adriamycin, campthothecin, and ionizing radiation induces NF-B activation. We found, however, that DNA damage failed to activate NF-B in RIP−/− fibroblasts. The induction of IB␣ degradation by DNA damage was normal in TNF-R1−/−, TRAF2−/−, TRAF5−/− and FADD−/− fibroblasts or when de novo protein synthesis was blocked. More importantly, the reconstitution of RIP expression in RIP−/− cells restores DNA damage-induced NF-B activation. We also found that RIP forms a complex with IKK in response to DNA damage. Therefore, our study provides a possible mechanism for the initiation of the cytoplasmic signaling to activate NF-B in response to DNA damage.