(C₆H₅CH₂NH₃)₂CuBr₄: A Lead-Free, Highly Stable Two-Dimensional Perovskite for Solar Cell Applications

The toxicity and the instability of lead-based perovskites might eventually hamper the commercialization of perovskite solar cells. Here, we present the optoelectronic properties and stability of a two-dimensional layered (C₆H₅CH₂­NH₃)₂CuBr₄ perovskite. This material has a low <i>E</i>_g of 1.81 eV and high absorption coefficient of ∼1 × 10⁵ cm^–1 at the most intensive absorption at 539 nm, implying that it is suitable for light-harvesting in thin film solar cells, especially in tandem solar cells. Furthermore, X-ray diffraction (XRD), ultraviolet–visible (UV–vis) absorption spectra, and thermogravimetric analysis (TGA) confirm the high stability toward humidity, heat, and ultraviolet light. Initial studies produce a mesoscopic solar cell with a power conversion efficiency of 0.2%. Our work may offer some useful inspiration for the further investigation of environment-friendly and stable organic–inorganic perovskite photovoltaic materials

C/EBPδ Deficiency Sensitizes Mice to Ionizing Radiation-Induced Hematopoietic and Intestinal Injury

<div><p>Knowledge of the mechanisms involved in the radiation response is critical for developing interventions to mitigate radiation-induced injury to normal tissues. Exposure to radiation leads to increased oxidative stress, DNA-damage, genomic instability and inflammation. The transcription factor CCAAT/enhancer binding protein delta (<i>Cebpd</i>; C/EBPδ is implicated in regulation of these same processes, but its role in radiation response is not known. We investigated the role of C/EBPδ in radiation-induced hematopoietic and intestinal injury using a <i>Cebpd</i> knockout mouse model. <i>Cebpd</i>−/− mice showed increased lethality at 7.4 and 8.5 Gy total-body irradiation (TBI), compared to <i>Cebpd</i>+/+ mice. Two weeks after a 6 Gy dose of TBI, <i>Cebpd</i>−/− mice showed decreased recovery of white blood cells, neutrophils, platelets, myeloid cells and bone marrow mononuclear cells, decreased colony-forming ability of bone marrow progenitor cells, and increased apoptosis of hematopoietic progenitor and stem cells compared to <i>Cebpd+/+</i> controls. <i>Cebpd</i>−/− mice exhibited a significant dose-dependent decrease in intestinal crypt survival and in plasma citrulline levels compared to <i>Cebpd+/+</i> mice after exposure to radiation. This was accompanied by significantly decreased expression of γ-H2AX in <i>Cebpd</i>−/− intestinal crypts and villi at 1 h post-TBI, increased mitotic index at 24 h post-TBI, and increase in apoptosis in intestinal crypts and stromal cells of <i>Cebpd</i>−/− compared to <i>Cebpd+/+</i> mice at 4 h post-irradiation. This study uncovers a novel biological function for C/EBPδ in promoting the response to radiation-induced DNA-damage and in protecting hematopoietic and intestinal tissues from radiation-induced injury.</p></div

Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice

<div><p>During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (¹⁶O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose ¹⁶O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose ¹⁶O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body ¹⁶O (600 MeV/n) irradiation. The effects of ¹⁶O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose ¹⁶O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of ¹⁶O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of ¹⁶O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of ¹⁶O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.</p></div

<i>Cebpd−/−</i> mice showed increased radiosensitivity to TBI.

<p>Thirty-day survival of <i>Cebpd−/−</i> mice and <i>Cebpd+/+</i> control mice exposed to 7.4 Gy (n = 7 per genotype) or 8.5 Gy (n = 12 mice per genotype) of TBI. <i>P = 0.02</i> for 7.4 Gy; <i>P</i><0.0001 for 8.5 Gy, as calculated by Logrank (Mantel-Cox) test. The numbers in parentheses indicate the number of animals that survived.</p

¹⁶O TBI caused reductions in percentages and numbers of HPCs, LSK cells and HSCs at three months after exposure.

<p>HPCs (Lin^-Sca1^-c-kit^- cells), LSK cells (Lin^-Sca1⁺c-kit⁺cells) and HSCs (Lin^-Sca1⁺c-kit⁺CD150⁺CD48^- cells) in BM were measured three months after 0.05 Gy, 0.1 Gy, 0.25 Gy, and 1.0 Gy ¹⁶O TBI. The frequencies (panel A) and numbers (panel B) of HPCs, LSK cells and HSCs from total bone marrow cells in each mouse are presented as means ±SD (n = 5). The statistical significance for differences between the control group (CTL) and each of the irradiated groups is indicated by asterisks. *p<0.05, **p<0.01, ***p<0.001 as determined by one-way ANOVA, followed by Tukey-Kramer test for individual comparisons.</p

¹⁶O TBI drives HSCs from quiescence into the cell cycle.

<p>Lin⁻cells were isolated from control (CTL) and irradiated (TBI) mice 2 weeks after 0.1, 0.25 and 1.0 Gy TBI. Cell cycle was measured by flow cytometry using Ki-67 and 7-AAD double staining in BM HPCs and HSCs from control and irradiated mice. (A-C) The percentages of G0, G1 and G2SM phases in BM HPCs, LSK cells and HSCs after TBI are presented as mean ± SD (n = 5). The distribution of cell cycle phases in HPCs, LSK cells and HSCs was analyzed by Chi-Square test as indicated by X² (HPC, X² = 19.084, p<0.05; LSK cells, X² = 6.486, p<0.05; HSCs, X² = 33.853, p<0.05). The statistical significance for the difference in each cell cycle phase between the control groups and irradiated groups is indicated by asterisks. *p<0.05, **p<0.01, ***p<0.001 by one-way ANOVA analysis.</p

<i>Cebpd−/−</i> mice had increased apoptosis and mitotic index and decreased levels of γ-H2AX in intestinal crypts, post-TBI.

<p>(A) Representative images of radiation-induced DNA fragmentation (TUNEL, green staining), DNA-damage marker γ -H2AX (red staining), and cellular nuclei (DAPI, blue staining) of proximal jejunums harvested from <i>Cebpd +/+</i> and <i>Cebpd</i>−/− mice at indicated times after exposure to 7.4 Gy TBI (magnification 10X). (B, C) Quantification of TUNEL-positive cells in intestinal crypts and stromal cells of the villi at indicated time-points after exposure to IR. (D, E) Quantification of γ-H2AX expression levels in intestinal crypts and villi at indicated time-points after exposure to IR. Values are presented as mean ± SEM, n = 4 per genotype per group. (F) Proximal jejunums of <i>Cebpd+/+</i> and <i>Cebpd</i>−/− mice were harvested at 0 h (No IR) and 24 h (IR) after exposure to 7.4 Gy TBI; representative images of immunohistochemical staining of phospho-histone H3 (Ser28) taken at 40× magnification. (G) Phospho-histone H3 (Ser28)-positive cells across approximately 100 intestinal crypts from unirradiated (No IR) and irradiated (IR) <i>Cebpd +/+</i> and <i>Cebpd</i>−/− mice were scored and represented as mean ± SEM, n = 4 per group.</p

<i>Cebpd−/−</i> deficiency enhanced radiation-induced myelosuppression.

<p>Peripheral blood B cells, T cells, and myeloid cells from unirradiated (No IR) and irradiated (IR) <i>Cebpd+/+</i> and <i>Cebpd</i>−/− mice (n = 3/genotype) were enumerated 14 days after exposure to 6 Gy TBI by phenotyping (A, C, E) and expressed as percent of total WBCs (B, D, F). All data are represented as mean ± SEM.</p

¹⁶O TBI causes persistent increases in DNA damage in HSCs but not in HPCs two weeks after the exposure.

<p>(A) Representative analysis of DNA damage measured in Lin^- cells by flow cytometry using γH2AX staining in BM HPCs and HSCs from control and 1.0 Gy¹⁶O TBI mice. The histograms indicate γH2AX MFI from a representative experiment. (B) The γH2AX MFI in BM HPCs and HSCs after TBI are presented as mean ± SD. (C) Sorted HPCs and HSCs from irradiated and non-irradiated mice were stained with γH2AX antibody. The numbers of foci in each cell were counted and expressed as mean ± SD. (D) The distribution of foci was expressed as the percentages of different numbers of foci in control and irradiated HSCs. The statistical significance for the difference between the control groups and each of irradiated groups is indicated by asterisks. *p<0.05, **p<0.01 by one-way ANOVA analysis.</p

¹⁶O TBI caused an increase in ROS production in LSK cells and HSCs three months after the exposure.

<p>(A) Lin^- cells were used to measured ROS production by staining with DCFDA and analyzed by flow cytometry. The DCF mean fluorescence intensity (MFI) in BM HPCs and HSCs are presented as means ± SD (n = 5). (B) Fold changes in relative gene expression for several antioxidant genes in sorted HPCs (left panel) and HSCs (right panel) from 1.0 Gy of ¹⁶O TBI and non-irradiated mice. (C) Lin^- cells were isolated and cell cycling was measured by cytometry using Ki-67 and 7-AAD double staining in HPCs and HSCs from control (CTL) and irradiated mice. The statistical significance for differences between the control group and each of the irradiated groups is indicated by asterisks. *p<0.05, **p<0.01, ***p<0.001 as determined by one-way ANOVA, followed by Tukey-Kramer test for individual comparisons.</p