DF 203 identified as target inhibiting atRAL- and 4-HNE-induced ARPE-19 cell death.

(A) Percentage inhibition of compounds on atRAL-induced ARPE-19 cell death. atRAL-treated group-only set as 0% inhibition, and untreated group set as 100% inhibition. Dotted line indicates 2xS.D. cutoff limit. The yellow line linked 2-dots replicates. (B) Dose-dependent inhibition of atRAL-mediated cell death of ARPE-19 by DF 203 measured by CytoTox-Glo. (C) Dose-dependent inhibition of 4-HNE mediated cell death of ARPE-19 by DF203 measured by PI. Each data point (B-C) represents biological replicates (n = 3–4), and indicated as mean±S.D.. Non-parametric Kruskal-Wallis test was applied for statistical analysis. * p<0.05, ** p<0.01 and *** p<0.001 compared to vehicle control.</p

Compound screen identification for prevention of both atRAL and 4-HNE-induced ARPE-19 cell death.

(A) Screening flowchart for the study, showing experiment treatment conditions, hit selection criteria and number of compounds passing each step. (B) Dose-dependent atRAL induction of ARPE-19 cell death, detection using CytoTox-Glo (EC50 = 12.0 μM, R2 = 0.9343). (C) Z’ factor for all assay plates was calculated to confirm screening quality based on vehicle control and 18 μM atRAL treatments. Outliers (Z’<0.7) were excluded from further analysis.</p

Improvement in Solid-State Dye Sensitized Solar Cells by <i>p</i>‑Type Doping with Lewis Acid SnCl₄

The Lewis acid SnCl₄ is employed as a <i>p</i>-type dopant for 2,2′,7,7′-tetrakis­(<i>N</i>,<i>N</i>-di-<i>p</i>-methoxyphenylamine)-9,9′-spirobifluorene (spiro-OMeTAD) for the solution process in solid-state dye sensitized solar cell. The UV–vis absorption spectra and time-resolved photoluminescence (PL) spectra are used to investigate the doping level of spiro-OMeTAD with a <i>p</i>-type dopant, indicating the strong molecular acceptor of SnCl₄. X-ray photoelectron spectra (XPS) exhibiting close energy shifts of the Fermi level toward HOMO are observed when adding Li salt or SnCl₄. A significant enhancement in fill factor of the photovoltaic devices, corresponding to the power conversion efficiency, is observed when doping with SnCl₄. This is attributed to the low charge transport resistance of the hole transport film and high hole injection efficiency from the hole transport material to the counter electrode

iPS-RPE has lower expression of apoptotic related genes compared to ARPE-19.

mRNA from both ARPE-19 and iPS-RPE was collected and the expression levels of apoptotic related genes, such as CASP8, BAX, and FAS, were evaluated using qPCR. The relative expression levels were normalized to the relevant gene expression in ARPE-19. Each data point represents biological replicates (n = 3–4) and is indicated as mean±S.D. Statistical analysis was performed using the non-parametric Mann-Whitney test. ** p (TIF)</p

AhR agonists prevent both atRAL and 4-HNE-induced ARPE-19 cell death.

(A) Measurement of CYP1A1 transcription in ARPE-19 after dosed treatment with AhR agonists DF 203, FICZ and Kynurenic Acid. CYP1A1 gene expression levels were normalized to β-actin. (B-C) atRAL and 4-HNE mediated cell death inhibition after pre-treatment with AhR agonists, measured by CytoTox-Glo (B) or PI (C). Each data point represents biological replicates (n = 3–4) and indicated as mean±S.D. Non-parametric Kruskal-Wallis test was applied for statistical analysis. * p<0.05 and ** p<0.01 compared to vehicle control.</p

atRAL and 4-HNE cause ARPE-19 cell death in dose- and time-dependent manners.

atRAL and 4-HNE-induced ARPE-19 cell death was visualized and analyzed using PI staining and IncuCyte. (A) The represented pictures of atRAL or 4-HNE-induced ARPE-19 cell death with indicated concentrations at 24 h post-treatment. The dose and time responses of atRAL (B) and 4-HNE (C) induced-cell death were quantified by the number of PI positive cells. Each data point represents biological replicates (n = 3–4), and indicated as mean±S.D. (TIF)</p

Schematic mechanism of AhR agonism preventing toxin-induced RPE death.

Various toxins can induce different types of cell death. In ARPE-19 cells, all-trans retinal (atRAL) induces apoptosis, while 4-hydroxynonenal (4-HNE) induces necrotic cell death. Activation of the aryl hydrocarbon receptor (AhR) leads to the upregulation of several downstream signaling pathways, which may include enzymes and other factors that can prevent cell death caused by these toxins. Figure created with BioRender.com.</p

atRAL induces apoptosis while 4-HNE induces necroptosis in ARPE-19 cells.

(A-B) Analysis of general cell death (PI) and caspase3/7 mediated apoptosis (CellEvent) following atRAL (A) and 4-HNE (B) treatments. (C-D) Quantification of atRAL- or 4-HNE-mediated ARPE-19 cell death using PI following pretreatment with increasing doses of Z-VAD (C) or Nec-1 (D) before challenge. Each data point represents biological replicates (n = 3–4) with five images captured per replicate and indicated as mean±S.D. Non-parametric Kruskal-Wallis test was applied for statistical analysis. * p<0.05, ** p<0.01 and *** p<0.001 compared to vehicle control.</p

AhR agonists could prevent 4-HNE but not atRAL induced iPS-RPE cell death.

(A-B) Analysis of general cell death (PI) following atRAL (A) and 4-HNE (B) treatments. (C-D) AhR agonist effects on atRAL (C) and 4-HNE (D) mediated iPS-RPE cell death, measured by PI staining. Each data point represents biological replicates (n = 3–4) and indicated as mean±S.D. Non-parametric Kruskal-Wallis test was applied for statistical analysis. * p<0.05 and *** p<0.001 compared to vehicle control.</p

Fully Printable Mesoscopic Perovskite Solar Cells with Organic Silane Self-Assembled Monolayer

By the introduction of an organic silane self-assembled monolayer, an interface-engineering approach is demonstrated for hole-conductor-free, fully printable mesoscopic perovskite solar cells based on a carbon counter electrode. The self-assembled silane monolayer is incorporated between the TiO₂ and CH₃NH₃PbI₃, resulting in optimized interface band alignments and enhanced charge lifetime. The average power conversion efficiency is improved from 9.6% to 11.7%, with a highest efficiency of 12.7%, for this low-cost perovskite solar cell