Chronotoxici-Plate Containing Droplet-Engineered Rhythmic Liver Organoids for Drug Toxicity Evaluation.

The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi-timepoint drug administration strategies across a wide range of drugs. Here, droplet-engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici-plate as an in vitro high-throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time-dependent variations are demonstrated in toxicity on the Chronotoxici-plate, highlighting the importance of considering time-dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing.

NiOx for interface and work function engineering in carbon-based all-inorganic perovskite solar cells.

Carbon-based all-inorganic perovskite solar cells (C-IPSCs) are stable, upscalable and have low CO2-footprint to fabricate. However, they are inefficient in converting light to electricity due to poor hole extraction at perovskite/carbon interface. Here we enable an efficient hole extraction in C-IPSCs with the aid of inorganic p-type nickel oxide nanoparticles (NiOx-NPs) at the interface and in carbon. By tailoring the work function (WF) of carbon, and reducing the energy-level misalignment at the perovskite/carbon interface, NiOx-NPs enable efficient hole transfer, reduce charge recombination and minimize energy loss. As a result, we report 15.01% and 11.02% efficiencies for CsPbI2Br and CsPbIBr2 C-IPSCs, respectively, with a high open-circuit voltage of ∼1.3 V. Unencapsulated interface-modified CsPbI2Br devices maintained 92.8% of their initial efficiency at ambient conditions after nearly 2,000 h; and 94.6% after heating at 60 °C for 170 h. This strategy to tailor carbon interface with perovskite offers an important knob in improving C-IPSCs performance.