Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported that iron deficiency had been implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis. Our in vitro models show the changes in protein levels of ferroptosis marker and enhanced lipid peroxidation level during oxidative stress. Safranin O staining, hematoxylin‐eosin staining, and immunohistochemical were used to assess the IVDD after 8 weeks of surgical procedure in vivo. Treatment with ferrostatin‐1, deferoxamine, and RSL3 demonstrate the role of ferroptosis in tert‐butyl hydroperoxide (TBHP)‐treated annulus fibrosus cells (AFCs) and nucleus pulposus cells (NPCs). Ferritinophagy, nuclear receptor coactivator 4 (NCOA4)‐mediated ferritin selective autophagy, is originated during the process of ferroptosis in response to TBHP treatment. Knockdown and overexpression NCOA4 further prove TBHP may induce ferroptosis of AFCs and NPCs in an autophagy‐dependent way. These findings support a role for oxidative stress‐induced ferroptosis in the pathogenesis of IVDD.

Estradiol could protect osteoblast against apoptosis, and apoptosis and autophagy were extensively and intimately connected. The aim of the present study was to test the hypothesis that autophagy was present in osteoblasts under serum deprivation and estrogen protected against osteoblast apoptosis via promotion of autophagy. MC3T3-E1 osteoblastic cells were cultured in a serum-free and phenol red-free minimal essential medium (α-MEM). Ultrastructural analysis, lysosomal activity assessment and monodansycadaverine (MDC) staining were employed to determine the presence of autophagy, and real time PCR was used to evaluate the expression of autophagic markers. Meanwhile, the osteoblasts were transferred in a serum-free and phenol red-free α-MEM containing either vehicle or estradiol. Apoptosis and autophagy was assessed by using the techniques of real-time PCR, Western blot, immunofluorescence assay, and flow cytometry. The possible pathway through which estrogen promoted autophagy in the serum-deprived osteoblasts was also investigated. Real-time PCR demonstrated the expression of LC3, beclin1 and ULK1 genes in osteoblasts under serum deprivation, and immunofluorescence assay verified high expression of proteins of these three autophagic bio-markers. Lysosomes and autolysosomes accumulated in the cytoplasm of osteoblasts were also detected under transmission electron microscopy, MDC staining and lysosomal activity assessment. Meanwhile, estradiol significantly decreased the expression of proteins of the bio-markers of apoptosis, and at the same time increased the expression of proteins of the bio-markers of autophagy in the serum-deprived osteoblasts. Furthermore, the estradiol-promoted autophagy in serum-deprived osteoblasts could be blocked by estrogen receptor (ER) antagonist (ICI 182780), and estradiol failed to rescue the cells pretreated with an inhibitor of vacuolar ATPase (bafilomycin A) from apoptosis. Serum deprivation resulted in apoptosis through activation of Caspase-3 and induced autophagy through inhibition of phospho-mammalian target of rapamycin (p-mTOR). Both 3-methyladenine (3MA) and U0126 led to increase of apoptosis in osteoblasts with serum deprivation. Estradiol failed to over-ride the inhibitory effect of 3MA on phosphorylation of AKT but directly led to dephosphorylation of mTOR and upregulation of LC3 protein expression. However, the estradiol-enhanced LC3 protein expression was significantly suppressed by U0126 through inhibition of phosphorylation of extracellular signal-regulated kinase (ERK). Estradiol rescued osteoblast apoptosis via promotion of autophagy through the ER-ERK-mTOR pathway.

We describe a simplified system of laser-driven flyer plates for shock compression science and shock spectroscopy. We used commercially available one-box Nd:YAG lasers and beam homogenization solutions to create two launch systems, one based on a smaller (400 mJ) YAG laser and an inexpensive diffusive optic, and one based on a larger (2500 mJ) laser and a diffractive beam homogenizer. The flyer launch, flight, and impact processes were characterized by an 8 GHz fiberoptic photon Doppler velocimeter. We investigated effects of different substrates, adhesives, absorbers, ablative layers, and punching out disks from continuous foils versus fabricating individual foil disks, and found that a simple metal foil epoxied to a glass window was satisfactory in almost all cases. Our simplified system launched flyer plates with velocities up to 4.5 km s(-1) and kinetic energies up to 250 mJ that can drive sustained steady shocks for up to 25 ns. The factor that limits these velocities and energies is the laser fluence that can be transmitted through the glass substrate to the flyer surface without optical damage. Methods to increase this transmission are discussed. Reproducible flyer launches were demonstrated with velocity variations of 0.06% and impact time variations of 1 ns. The usefulness of this flyer plate system is demonstrated by Hugoniot equation of state measurements of a polymer film, emission spectroscopy of a dye embedded in the polymer, and impact initiation and emission spectroscopy of a reactive material consisting of nanoscopic fuel and oxidizer particles.

Polynitrogen compounds especially pentazolate anion complexes recently have attracted substantial attention due to their promising potential as high-energy-density materials. Here, using a machine-learning-accelerated crystal structure search method and first-principles calculations, we predict a new hybrid compound by inserting a large fraction of nitrogen into alkaline-earth metals. It is a new stoichiometric type MN10 (M = Be, Mg), which possesses a metal-centering octahedral pentazolate framework with the space group Fdd2. This type of ionic-like molecular crystal is found to be energetically more favorable than the mixtures of M3N2 or MN4 compounds and pure nitrogen and is possibly synthesized at relatively low pressures (around 12 GPa for MgN10). The ab initio molecular dynamics simulations show that they are metastable and can be quenched to ambient conditions once synthesized at high pressure. Moreover, decomposition of this polymeric MN10 structure can release a large amount of energy and shows high performance in detonation. The detonation velocity and pressure of BeN10 are about twice and 4 times that of trinitrotoluene, respectively.