Overview of Ferroptosis and Synthetic Lethality Strategies

Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery.     

Present Status and Future Prospects of Laser Fusion Research at ILE Osaka University

Reviewed are the present status and future prospects of the laser fusion research at the ILE Osaka.The Gekko XII and Peta Watt laser system have been operated for investigating the implosion hydrodynamics,fast ignition, and the relativistic laser plasma interactions and so on.In particular,the fast ignition experiments with cone shell target have been in progress as the UK and US-Japan collaboration programs.In the experiments,the imploded high density plasmas are heated by irradiating 500 J level peta-watt laser pulse.The thermal neutron yield is found to increase by three orders of magnitude by injecting the peta-watt laser into the cone shell target.The Rayleigh-Taylor instability experiment results are also reviewed is this paper.     

DNA taken into Bacillus subtilis competent cells by lysed-protoplast transformation is not ssDNA but dsDNA

Competent Bacillus subtilis incorporates whole-genome DNA (4215 kb) from the protoplast lysate of B. subtilis subtilis [Akamatsu, T. and Taguchi, H., Biosci. Biotechnol. Biochem., 65, 823-829 (2001)]. A continuous incorporated DNA is longer than 1500 kb [J. Biosci. Bioeng., 101, 257-262 (2006)]. Whether the incorporated DNA is single-stranded (ssDNA) or double-stranded DNA (dsDNA) has been studied by examining the transforming activity of the incorporated DNA. B. subtilis BEST7027 was used as the donor strain, which has a heterologous region consisting of the 145 kb region of the Synechocystis sp. PCC6803 genome and erm gene. The donor DNA was transferred to a wild-type or a recA recipient strain (AYG2 or SYN9), and protoplast lysate was prepared from the transformants and used as the donor DNA source for the second recipient strain (AU1 or AV1). The intergenote region showed a significant transforming activity. When DNase I was added to both cells collected from the first transformation mixture and the following protoplastization, the result was similar to that obtained without DNase I. All of the observations strongly suggest that the incorporated DNA is dsDNA, and the transformation of competent B. subtilis by DNA in protoplast lysate is different from that by purified DNA taken up conventionally.     

Fate of transforming bacterial genome following incorporation into competent cells of Bacillus subtilis: a continuous length of incorporated DNA

In contrast to the conventional transformation of Bacillus subtilis using purified DNA, those using DNA in lysed protoplasts have a high transformation efficiency and enable whole-genome transfer into competent B. subtilis [Akamatsu, T. and Taguchi, H., Biosci. Biotechnol. Biochem., 65, 823-829 (2001)]. Here, we examined the length of incorporated continuous DNA by analyzing the cotransfer ratio with selected and unselected markers, on the basis of a new experimental design. The cotransfer ratio of a selected marker with an unselected marker on the opposite side of the genetic map of the B. subtilis chromosome was about 5.6% and could be interpreted as congression (double transformation) ratio. In the wild-type strain, the cotransfer ratio of cysA (113 kb position on 4215 kb of B. subtilis chromosome) with metC (1384 kb) and leuB (2891 kb) was 0.77%, twice the value (5.6% x 5.6%=0.31%) calculated from the congression ratio. Moreover, in a genetic background, the cotransfer ratios of metC with cysA and leuB, and metC with cysA and arg1 (3012 kb) were 2.7% and 7.2%, respectively. These results strongly suggest that the length of continuous DNA incorporated into B. subtilis is most probably greater than 1271 kb. When the DNA from the protoplast lysate was fragmented by mixing, the cotransfer ratios of arg1 with metC, and arg1 with metC and trpC (2374 kb) were 2.8% and 0.16%, respectively. A high cotransfer ratio (2.7-7.2%) could not, therefore, be obtained using the fragmented DNA. Based on these observations, we propose a working hypothesis on the mechanism of the transformation of competent B. subtilis by DNA in protoplast lysates (LP transformation).     

Synthesis of multilayered composite nanotube heterostructure; SiC–SiO2, C–SiO2, and C–SiC–SiO2 nanotubes

Three types of composite nanotube heterostructures (two double-layered and one triple-layered structure) are synthesized by simple heat treatment, forming SiC–SiO₂, C–SiO₂, and C–SiC–SiO₂ composite coaxial nanotubes. These multilayered composite nanotubes consist of several components with different electrical properties, for example, metal, semiconductor, and insulator components. In particular, C–SiC–SiO₂ triple-layered nanotubes with metallic, semiconducting, and insulating layers are synthesized for the first time. These multilayered nanotubes can be expected to find applications in nanoscale heterostructure electronic and optical devices.     

Nickel-free stainless steel avoids neointima formation following coronary stent implantation

SUS316L stainless steel and cobalt–chromium and platinum–chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N₂-gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni²⁺ was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni²⁺ increased levels of hypoxia inducible factor protein-1α (HIF-1α) and its target genes in cultured smooth muscle cells. HIF-1α and their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform.     

Degradation behavior of anode-supported solid oxide fuel cell using LNF cathode as function of current load

We investigated the effect of current loading on the degradation behavior of an anode-supported solid oxide fuel cell (SOFC). The cell consisted of LaNi_0.6Fe_0.4O₃ (LNF), alumina-doped scandia stabilized zirconia (SASZ), and a Ni-SASZ cermet as the cathode, electrolyte, and anode, respectively. The test was carried out at 1073 K with constant loads of 0.3, 1.0, 1.5, and 2.3 A cm⁻². The degradation rate, defined by the voltage loss during a fixed period (about 1000 h), was faster at higher current densities. From an impedance analysis, the degradation depended mainly on increases in the cathodic resistance, while the anodic and ohmic resistances contributed very little. The cathode microstructures were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).     

Promotion of initial cell adhesion on trisuccinimidyl citrate-modified nickel-free high-nitrogen stainless steel

The surface of nickel-free high-nitrogen stainless steel (HNS) was modified with a citric acid-based cross-linker, trisuccinimidyl citrate (TSC), to promote initial cell adhesion in external skeletal fixation pins. The remaining active ester groups on TSC-immobilized HNS reacted with the amino groups of serum proteins. The immobilized serum proteins formed cell recognition sites to promote the initial cell adhesion immediately after cell seeding. The amount of fibronectin, which is a typical cell adhesion protein, immobilized on the TSC-immobilized HNS surface was threefold greater than on the original HNS after only 15 min. The fibroblastic cell culture experiments showed that the initial cell adhesion was significantly enhanced on the TSC-immobilized HNS compared with the original HNS at 3 h. Furthermore, the cell adhesion activity of the TSC-immobilized HNS continued to promote cell proliferation even at 7 days. Therefore, TSC-immobilized HNS may enable the rapid integration of soft tissues through its reaction with the patient’s serum proteins and extracellular proteins around the surgical site.