Cardiotoxicity of Anti-PD-L1 Antibody and the Effect of Levothyroxine in Attenuating the Related Mortality in Mice

Background and objective Immune checkpoint inhibitors (ICIs) such as antibodies against programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), have shown remarkable efficacies in many subtypes of cancers. However, ICIs may also cause severe immune-related adverse events in the recipient patients. Recently, ICI-associated myocarditis have been reported in hundreds of patients worldwide, with a mortality rate of approximately 50% in these cases. This study aims to recapitulate the cardiotoxicity and explore the detoxicifying approaches to attenuate mortality caused by PD-1/PD-L1 inhibitors in healthy mice. Methods Six to eight-week-old C57BL/6 mice were inoculated with anti-PD-1 antibody (12.5 μg/g every 5 days for 6 injections), anti-PD-L1 antibody (10 μg/g once a week for 6 weeks), anti-PD-L1 antibody (with the same dosage described above) in combination with levothyroxine (0.25 μg/g, intraperitoneally injected half an hour before anti-PD-L1 antibody injection), or isotype control immunoglobulin IgG (10 μg/g once a week for 6 weeks). The ejection function of the hearts was detected by echocardiography, body temperature and blood pressure were detected by Mouse MonitorTM and non-invassive blood pressure minotor, and serum free thyroxine concentration was detected by The enzyme linked immunosorbent assay (ELISA). Results PD-L1 was expressed at different levels by the cardiomyocytes of the mice. The isotype control immunoglobulin and anti-PD-1 antibody did not cause death of the mice. The 12 mice receiving 3-6 injections of anti-PD-L1 antibody showed a significant increase in the heart-to-tibial ratio and cardiomyoctye degeneration, hyalinization and extravascular inflammatory cell infiltration. In addition, the serum thyroxine was mardedly decreased to 1/3 of that in the control group mice, and the blood pressure and body temperature were abnormally decreased in mice upon treatment with PD-L1 blockade. Eight of the 12 (66.7%) mice died from multiple intravenous injection of anti-PD-L1 antibody.Intraperitoneal injection of levothyroxine 30 min before the injection of anti-PD-L1 antibody significantly attenuated the mortality rate of the anti-PD-L1 antibody-treated mice. Conclusion The anti-PD-L1 antibody is cardiotoxic and lethal, and levothyroxine is able to rescue the mice from this immune checkpoint inhibitor-caused mortality

High efficiency ternary organic solar cells enabled by compatible dual-donor strategy with planar conjugated structures

Ternary organic solar cells (OSCs) have received extensive attention for improving the power conversion efficiency (PCE) of organic photovoltaics (OPVs). In this work, a novel donor material (ECTBD) consisting of benzodithiophene (BDT) central electron donor unit was developed and synthesized. The small molecular donor has the same central unit as PM6. The addition of ECTBD into PM6:Y6 system could improve the morphology of active blend layer. In addition, ECTBD showed good morphologically compatibility when blending with PM6:Y6 host, resulting in the improvement of fill factor and current density. As a result, the ternary devices based on PM6:ECTBD:Y6 ternary system achieved a highest PCE of 16.51% with fill factor of 76.24%, which was much higher than that of the binary devices (15.7%). Overall, this work provided an effective strategy to fabricate highly efficient ternary organic solar cells through design of the novel small molecular donor as the third component

A novel polymer donor based on dithieno[2,3-d:2 ',3 '-d '']benzo[1,2-b:4,5-b ']dithiophene for highly efficient polymer solar cells

A novel polymer donor based on dithieno[2,3-d:2 ',3 '-d '']benzo[1,2-b:4,5-b ']dithiophene for highly efficient polymer solar cell

Enhanced efficiency of organic solar cells via Si-based non-conjugated small-molecule electrolyte as cathode interlayer

As an important approach to commercialize organic solar cells (OSC), research on solution-processable and low-cost interfacial materials with universal applicability has attracted much attention. In this work, three new non-conjugated small-molecules electrolytes (NCSMEs) with silicon as the core atom and sulfonate ion as the terminal group were synthesized, which were further applied as cathode interlayers (CILs) in non-fullerene and fullerene based OSCs. As the result, the power conversion efficiency (PCE) of 15.57% for non-fullerene PM6:Y6-based and 8.96% for fullerene PTB7:PC71BM-based device was obtained, respectively. The improved performance was mostly attributed to the NCSMEs CILs which could mediate the energy barrier to form a better ohmic contact, enhance the charge transmission and collection efficiency, and decrease the charge recombination. It is noteworthy that the synthesized CILs could provide a new strategy for the potential applications of low-cost and highly efficient OSCs

Foldable Semitransparent Organic Solar Cells for Photovoltaic and Photosynthesis

Semitransparent organic solar cells (ST-OSCs) have attracted extensive attention for their potential greenhouse applications. Conventional ST-OSCs are typically based on indium tin oxide (ITO) electrodes which suffer from mechanical brittleness. Therefore, alternatives for ITO are required for realization of foldable-flexible ST-OSCs (FST-OSCs). Herein, flexible poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) electrodes are prepared as ITO alternatives via polyhydroxy compound (xylitol) microdoping and acid treatment. As a result, flexible opaque OSCs based on PBDB-T-2F:Y6 photoactive system yield a high efficiency of 14.20%. The desirable optical properties of modified PEDOT:PSS electrodes in the visible light region and PBDB-T-2F:Y6 photoactive layer in the near-infrared region facilitate the fabrication of FST-OSCs with over 10% efficiency and 21% average visible light transmittance. Those FST-OSCs also display excellent mechanical stability against bending and folding due to the xylitol doping, where over 80% of the initial efficiency can still be maintained even after 1000 folding cycles. Meanwhile, parallel comparisons between plants grown under direct sunlight with a FST-OSCs roof and those under direct sunlight yield very similar results in terms of branch sturdiness and hypertrophic leaves. The results pave the way for realizing high-performing FST-OSCs based on PEDOT:PSS electrodes that could utilize visible light for plant growth and infrared light for power generation