Ferroptosis is a newly defined programmed cell death process with the hallmark of the accumulation of iron‐dependent lipid peroxides. The term was first coined in 2012 by the Stockwell Lab, who described a unique type of cell death induced by the small molecules erastin or RSL3. Ferroptosis is distinct from other already established programmed cell death and has unique morphological and bioenergetic features. The physiological role of ferroptosis during development has not been well characterized. However, ferroptosis shows great potentials during the cancer therapy. Great progress has been made in exploring the mechanisms of ferroptosis. In this review, we focus on the molecular mechanisms of ferroptosis, the small molecules functioning in ferroptosis initiation and ferroptosis sensitivity in different cancers. We are also concerned with the new arising questions in this particular research area that remains unanswered.

SummaryPlant basic helix-loop-helix (bHLH) transcription factors play essential roles in abiotic stress tolerance. However, most bHLHs have not been functionally characterized. Here, we characterized the functional role of a bHLH transcription factor from Arabidopsis, AtbHLH112, in response to abiotic stress.AtbHLH112 is a nuclear-localized protein, and its nuclear localization is induced by salt, drought and abscisic acid (ABA). In addition, AtbHLH112 serves as a transcriptional activator, with the activation domain located at its N-terminus.In addition to binding to the E-box motifs of stress-responsive genes, AtbHLH112 binds to a novel motif with the sequence 'GG[GT]CC[GT] [GA][TA]C' (GCG-box). Gain-and loss-offunction analyses showed that the transcript level of AtbHLH112 is positively correlated with salt and drought tolerance. AtbHLH112 mediates stress tolerance by increasing the expression of P5CS genes and reducing the expression of P5CDH and ProDH genes to increase proline levels. AtbHLH112 also increases the expression of POD and SOD genes to improve reactive oxygen species (ROS) scavenging ability.We present a model suggesting that AtbHLH112 is a transcriptional activator that regulates the expression of genes via binding to their GCG-or E-boxes to mediate physiological responses, including proline biosynthesis and ROS scavenging pathways, to enhance stress tolerance.

Ba 1.8−x Sr x SiO 4 :0.1Ce 3+ ,0.1Na + (x = 0−1.8) phosphors were prepared by a high-temperature solid-state reaction. The emission peaks of Ba 1.8−x Sr x SiO 4 :0.1Ce 3+ ,0.1Na + shift from 391 to 411 nm with increasing Sr 2+ content under excitation by a UV light at around 360 nm. Ba 0.4 Sr 1.4 SiO 4 :0.1Ce 3+ ,0.1Na + phosphor exhibits the best performance of luminescence, whose absolute quantum efficiency is 97.2%, and the emission intensity at 150 °C remains 90% of that at room temperature. The effect of replacing Ba 2+ by Sr 2+ on the red shift of the emission band and the increase of quantum efficiency (QE) and thermal stability (TS) was investigated in detail based on the Rietveld refinements, Raman spectra, thermoluminescence, and decay curves, etc. The performance of UV chip-based pc-LEDs indicates that Ba 0.4 Sr 1.4 SiO 4 :0.1Ce 3+ ,0.1Na + can be a promising blue phosphor for white-emitting pc-LEDs.

WRKY transcription factors are involved in various biological processes, such as development, metabolism and responses to stress. However, their exact roles in abiotic stress tolerance are largely unknown. Here, we demonstrated a working model for the function of a WRKY gene (ThWRKY4) from Tamarix hispida in the stress response. ThWRKY4 is highly induced by abscisic acid (ABA), salt and drought in the early period of stress (stress for 3, 6, or 9 h), which can be regulated by ABF (ABRE binding factors) and Dof (DNA binding with one finger), and also can be crossregulated by other WRKYs and autoregulated as well. Overexpression of ThWRKY4 conferred tolerance to salt, oxidative and ABA treatment in transgenic plants. ThWRKY4 can improve the tolerance to salt and ABA treatment by improving activities of superoxide dismutase and peroxidase, decreasing levels of O2 (-) and H2O2, reducing electrolyte leakage, keeping the loss of chlorophyll, and protecting cells from death. Microarray analyses showed that overexpression of ThWRKY4 in Arabidopsis leads to 165 and 100 genes significantly up- and downregulated, respectively. Promoter scanning analysis revealed that ThWRKY4 regulates the gene expression via binding to W-box motifs present in their promoter regions. This study shows that ThWRKY4 functions as a transcription factor to positively modulate abiotic stress tolerances, and is involved in modulating reactive oxygen species.

Photoluminescence quantum efficiency (QE) and thermal stability are important for phosphors used in phosphor-converted light-emitting diodes (pc-LEDs). LiSrCa(SiO):0.03Ce (-0.7 ≤ x ≤ 1.0) phosphors were designed from the initial model of LiSrCa(SiO):Ce, and their single-phased crystal structures were found to be located in the composition range of -0.4 ≤ x ≤ 0.7. Depending on the substitution of Sr for Ca ions, the absolute QE value of blue-emitting composition-optimized LiSrCa(SiO):0.03Ce reaches ∼94%, and the emission intensity at 200 °C remains 95% of that at room temperature. Rietveld refinements and Raman spectral analyses suggest the increase of crystal rigidity, increase of force constant in CeO, and decrease of vibrational frequency by increasing Sr content, which are responsible for the enhanced quantum efficiency and thermal stability. The present study points to a new strategy for future development of the pc-LEDs phosphors based on local structures correlation via composition screening.

ROS functions as a second messenger and modulates multiple signaling pathways under the physiological conditions. However, excessive intracellular ROS causes damage to the molecular components of the cell, which promotes the pathogenesis of various human diseases. Cardiovascular diseases are serious threats to human health with extremely high rates of morbidity and mortality. Dysregulation of cell death promotes the pathogenesis of cardiovascular diseases and is the clinical target during the disease treatment. Numerous studies show that ROS production is closely linked to the cell death process and promotes the occurrence and development of the cardiovascular diseases. In this review, we summarize the regulation of intracellular ROS, the roles of ROS played in the development of cardiovascular diseases, and the programmed cell death induced by intracellular ROS. We also focus on anti-ROS system and the potential application of anti-ROS strategy in the treatment of cardiovascular diseases.

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Background and Aims Because of a paucity of effective treatment options, metastasis is still a major cause for HCC‐associated mortality. The molecular mechanism of inflammation‐induced HCC metastasis is open for study. Here, we characterized the function of solute carrier family 7 member 11 (SLC7A11) in inflammation‐related HCC metastasis and probed therapy strategies for this subpopulation of patients. Approach and Results Elevated expression of SLC7A11 was positively correlated with poor tumor differentiation, and higher tumor‐nodule‐metastasis stage, and indicated poor prognosis in human HCC. SLC7A11 increased HIF1α expression through reducing α‐ketoglutarate (αKG) level by exporting glutamate. SLC7A11 up‐regulated programmed death ligand 1 (PD‐L1) and colony‐stimulating factor 1 (CSF1) expression through αKG‐HIF1α cascade. SLC7A11 overexpression in HCC cells promoted intratumoral tumor‐associated macrophage (TAM) and myeloid­derived suppressor cell (MDSC) infiltration through the CSF1/colony‐stimulating factor 1 receptor (CSF1R) axis, whereas knockdown of CSF1 attenuated SLC7A11‐mediated intratumoral TAM and MDSC infiltration and HCC metastasis. Depletion of either TAMs or MDSCs decreased SLC7A11‐mediated HCC metastasis. Furthermore, the combination of CSF1R inhibitor BZL945 and anti‐PD‐L1 antibody blocked SLC7A11‐induced HCC metastasis. In addition, IL‐1β up‐regulated SLC7A11 expression through the interleukin‐1 receptor type 1 (IL‐1R1)/extracellular signal‐regulated kinase/specificity protein 1 pathway. SLC7A11 knockdown impaired IL‐1β‐promoted HCC metastasis. Anakinra, an IL‐1R1 antagonist, reversed IL‐1β‐promoted HCC metastasis. In human HCC tissues, SLC7A11 expression was positively associated with HIF1α, PD‐L1, and CSF1 expression and intratumoral TAM and MDSC infiltration. Conclusions IL‐1β‐induced SLC7A11 overexpression up‐regulated PD‐L1 and CSF1 through the αKG/HIF1α axis, which promoted TAM and MDSC infiltration. Interruption of this oncogenic loop may provide a promising therapy strategy for the inhibition of SLC7A11‐mediated HCC metastasis.