Miniaturization during a Silurian environmental crisis generated the modern brittle star body plan

Pivotal anatomical innovations often seem to appear by chance when viewed through the lens of the fossil record. As a consequence, specific driving forces behind the origination of major organismal clades generally remain speculative. Here, we present a rare exception to this axiom by constraining the appearance of a diverse animal group (the living Ophiuroidea) to a single speciation event rather than hypothetical ancestors. Fossils belonging to a new pair of temporally consecutive species of brittle stars (Ophiopetagno paicei gen. et sp. nov. and Muldaster haakei gen. et sp. nov.) from the Silurian (444–419 Mya) of Sweden reveal a process of miniaturization that temporally coincides with a global extinction and environmental perturbation known as the Mulde Event. The reduction in size from O. paicei to M. haakei forced a structural simplification of the ophiuroid skeleton through ontogenetic retention of juvenile traits, thereby generating the modern brittle star bauplan.

Improving the comprehensive performance of miniature MR rotary actuators using a lamellar excitation structure

Miniaturization has increasingly become a crucial prerequisite in various magnetorheological (MR) drive application scenarios. Owing to their high controllability and low response time, MR rotary actuators are developed for numerous feasible actuation solutions. However, the incident low degradation efficiency in the miniaturization limits the application of MR rotary actuators. In addition to torque capacity, structural simplification and easy machinability are also essential for miniaturization. In this study, a novel lamellar excitation structure (LES), which is interleaved with induction coils and ring-shaped iron cores, is proposed to improve the comprehensive performance of a miniature MR rotary actuator. The optimisation of the magnetic field distribution is realised by adopting an equivalent magnetic modelling method. The miniature MR actuator is incorporated into a turbine generator to evaluate the torque capability of the proposed LES-incorporated MR actuator via a kinematic model of the rotating shaft. The LES-incorporated MR rotary actuator demonstrates more favourable deceleration efficiency and torque capacity than conventional MR rotary actuators. The speed reduction per unit power Δn/P can be increased by 500% at most. The torque enhancement ratio-to-volume ratio (TEVR) value of LES is approximately 80 times higher than that of other optimised structures. We believe that this study is significant in improving the comprehensive performance of miniature MR rotary actuators, expanding the applications of MR actuators in miniaturised scenarios.

Discovery of Novel Small-Molecule Inhibitors of PD-1/PD-L1 Interaction via Structural Simplification Strategy

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.