Stem cell therapy may provide a safe and promising treatment for retinal diseases. Wet age-related macular degeneration (wet-AMD) is a leading cause of blindness in China. We developed a clinical-grade human embryonic stem cell (hESC) line, Q-CTS-hESC-2, under xeno-free conditions that differentiated into retinal pigment epithelial cells (Q-CTS-hESC-2-RPE). A clinical trial with three wet-AMD patients was initiated in order to study the safety and tolerance to Q-CTS-hESC-2-RPE cell transplants. The choroidal neovascularization membrane was removed and then a suspension of 1 × 106 Q-CTS-hESC-2-RPE cells were injected into a subfoveal pocket. The patients were followed for 12 months during which no adverse effects resulting from the transplant were observed. Anatomical evidence suggested the existence of new RPE-like cell layer in the previously damaged area. Visual and physiological testing indicated limited functional improvement, albeit to different degrees between patients. This study provides some promising early results concerning the use of transplanted hESC-RPE cells to alleviate wet-AMD.

Necroptosis is a form of regulated necrosis controlled by receptor-interacting kinase 1 (RIPK1 or RIP1), RIPK3 (RIP3), and pseudokinase mixed lineage kinase domain-like protein (MLKL). Increasing evidence suggests that necroptosis is closely associated with pathologies including inflammatory diseases, neurodegenerative diseases, and cancer metastasis. Herein, we discovered the small-molecule PK6 and its derivatives as a novel class of necroptosis inhibitors that directly block the kinase activity of RIPK1. Optimization of PK6 led to PK68, which has improved efficacy for the inhibition of RIPK1-dependent necroptosis, with an EC 50 of around 14–22 nM in human and mouse cells. PK68 efficiently blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptosis stimuli. PK68 displays reasonable selectivity for inhibition of RIPK1 kinase activity and favorable pharmacokinetic properties. Importantly, PK68 provides strong protection against TNF-α-induced systemic inflammatory response syndrome in vivo. Moreover, pre-treatment of PK68 significantly represses metastasis of both melanoma cells and lung carcinoma cells in mice. Together, our study demonstrates that PK68 is a potent and selective inhibitor of RIPK1 and also highlights its great potential for use in the treatment of inflammatory disorders and cancer metastasis.

All-inorganic CsPbI2Br, prized for its strong stability against thermal aging and light soaking, has attracted intensive attention. However, a large energy loss results from the serious energy level offset of 1.05 eV between CsPbI2Br and Spiro-MeOTAD, hindering the further efficiency improvement of perovskite solar cells. To address this issue, a moderate energy level (CsPbI2Br)1–x (CsPbI3) x layer has been introduced at the interface between CsPbI2Br and Spiro-MeOTAD to form a graded energy level alignment, the interpolation of which has offered the energy level gradient for reducing the resistance of hole transport. Correspondingly, the energy level tailoring has minimized the energy loss, and a remarkable V OC improved from 1.12 to 1.32 V, which is one of the highest values for CsPbI2Br-based solar cells. A relatively good thermal stability has also been validated. These good performances indicate that setting an intermediate energy level alignment will be a potential strategy for idealized device architecture to minimize energy loss.

Photodetectors (PDs), converting incident photons into electrical signals, play a crucial role in modern optoelectronic applications such as photo detection, optical communications, and imaging. [1-7] Owing to high material quality, broad chemical tunability, long carrier diffusion lengths, and high mobility, Pb based metal halide crystalline perovskites have attracted great attention for sensitive PD applications. [8-11] Despite their striking advances, the toxicity of Pb and stability issues have severely limited their practical commercialization. [12-14] Therefore, it is highly desirable and urgent to replace Pb with other metal alternatives which are less toxic, environ