MOGAT2

The development of highly reusable, affordable, and durable photocatalysts for the production of hydrogen peroxide (H₂O₂) remained a challenge. In this study, a homojunction photocatalyst (SPGCN) is constructed between phosphorylated g-C₃N₄ (PCN) and sulfur self-doped g-C₃N₄ (SCN) using a simple wet impregnation method. Later, the obtained SPGCN homojunction is transformed into hydrogel beads using carboxymethyl cellulose via an effective cross-linking strategy (SPGCN/CMC). The photocatalytic beads displayed a phenomenal H₂O₂ production of 3.5 mM under visible light illumination for 60 min. The SPGCN/CMC hydrogel beads showed a maximum reusability of 10 cycles with a decline of 1.5 mM H₂O₂ production. The improved photocatalytic efficiency is indicated by strengthened utilization of visible light via tuning of the band gap, suppressed recombination of electron-hole pairs, and higher separation efficiency through the effective construction of Z-scheme between the phosphorylated carbon nitride and the sulfur-self-doped carbon nitride present in the SPGCN/CMC beads. The mechanistic studies affirmed the dominant role of superoxide radicals in H₂O₂ production. The photocatalytic H₂O₂ production followed a highly selective two-electron reduction reaction. Overall, this study highlights the efficient engineering of carbon nitride-based materials towards artificial photosynthesis.

The purpose of study was to evaluate that kallistatin deficiency causes excessive production of reactive oxygen species and exacerbates neuronal injury after cardiac arrest. For in vitro study, kallistatin knockdown human neuronal cells were given ischemia-reperfusion injury, and the oxidative stress and apoptosis were evaluated. For clinical study, cardiac arrest survivors admitted to the ICU were divided into the good (CPC 1-2) and poor (CPC 3-5) 6-month neurological outcome groups. The serum level of kallistatin, Nox-1, H₂O₂ were measured. Nox-1 and H₂O₂ levels were increased in the kallistatin knockdown human neuronal cells with ischemia-reperfusion injury (p < 0.001) and caspase-3 was elevated and apoptosis was promoted (SERPINA4 siRNA: p < 0.01). Among a total of 62 cardiac arrest survivors (16 good, 46 poor), serum kallistatin were lower, and Nox-1 were higher in the poor neurological group at all time points after admission to the ICU (p = 0.013 at admission; p = 0.020 at 24 h; p = 0.011 at 72 h). At 72 h, H₂O₂ were higher in the poor neurological group (p = 0.038). Kallistatin deficiency exacerbates neuronal ischemia-reperfusion injury and low serum kallistatin levels were associated with poor neurological outcomes in cardiac arrest survivors.

Glucose and amino acid metabolism are critical for glioblastoma (GBM) growth, but little is known about the specific metabolic alterations in GBM that are targetable with FDA-approved compounds. To investigate tumor metabolism signatures unique to GBM, we interrogated The Cancer Genome Atlas for alterations in glucose and amino acid signatures in GBM relative to other human cancers and found that GBM exhibits the highest levels of cysteine and methionine pathway gene expression of 32 human cancers. Treatment of patient-derived GBM cells with the FDA-approved single cysteine compound N-acetylcysteine (NAC) reduced GBM cell growth and mitochondrial oxygen consumption, which was worsened by glucose starvation. Normal brain cells and other cancer cells showed no response to NAC. Mechanistic experiments revealed that cysteine compounds induce rapid mitochondrial H₂O₂ production and reductive stress in GBM cells, an effect blocked by oxidized glutathione, thioredoxin, and redox enzyme overexpression. From analysis of the clinical proteomic tumor analysis consortium (CPTAC) database, we found that GBM cells exhibit lower expression of mitochondrial redox enzymes than four other cancers whose proteomic data are available in CPTAC. Knockdown of mitochondrial thioredoxin-2 in lung cancer cells induced NAC susceptibility, indicating the importance of mitochondrial redox enzyme expression in mitigating reductive stress. Intraperitoneal treatment of mice bearing orthotopic GBM xenografts with a two-cysteine peptide induced H₂O₂ in brain tumors in vivo. These findings indicate that GBM is uniquely susceptible to NAC-driven reductive stress and could synergize with glucose-lowering treatments for GBM.