Blockade of the protein–protein interaction between the transmembrane protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating ...cancers. Using the technology of mirror‐image phage display, we developed the first hydrolysis‐resistant D‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound DPPA‐1 could bind PD‐L1 at an affinity of 0.51 μM in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that DPPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus D‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.
Protein chemical synthesis and mirror‐image phage display were combined to develop a proteolysis‐resistant D‐peptide antagonist (DPPA‐1) which targets the immune checkpoint protein PD‐L1 (the ligand for PD‐1, the programmed cell death protein 1). DPPA‐1 was found to inhibit the PD‐1/PD‐L1 protein–protein interaction at the cellular level. IgV=immunoglobulin‐like variable.
Structural damage detection is still a challenging problem owing to the difficulty of extracting damage‐sensitive and noise‐robust features from structure response. This article presents a novel ...damage detection approach to automatically extract features from low‐level sensor data through deep learning. A deep convolutional neural network is designed to learn features and identify damage locations, leading to an excellent localization accuracy on both noise‐free and noisy data set, in contrast to another detector using wavelet packet component energy as the input feature. Visualization of the features learned by hidden layers in the network is implemented to get a physical insight into how the network works. It is found the learned features evolve with the depth from rough filters to the concept of vibration mode, implying the good performance results from its ability to learn essential characteristics behind the data.
Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated ...parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep. We applied a daytime light-deprivation protocol (DD) mimicking jet-lag to screen drugs that alleviate sleep deprivation. Characteristically, classical sleep-aid compounds exhibited different forms of influence: phenobarbital and pentobarbital modified total sleep time, while melatonin only shortened the latency to sleep. Such results construct the basis for further research on sleep benefits in other treatments in Drosophila. We screened seven herb extracts, and found very diverse results regarding their effect on sleep regulation. For instance, Panax notoginseng and Withania somnifera extracts displayed potent influence on total sleep time, while Melissa officinalis increased the number of sleep episodes. By comparing these treatments, we were able to rank drug potency in different aspects of sleep regulation. Notably, we also confirmed the presence of sleep difficulties in a Drosophila Alzheimer's disease (AD) model with an overexpression of human Abeta, and recognized clear differences between the portfolios of drug screening effects in AD flies and in the control group. Overall, potential drug candidates and receipts for sleep problems can be identified separately for normal and AD Drosophila populations, outlining Drosophila's potential in drug screening tests in other populations if combined with the use of other genetic disease tools.
Improving charge extraction and suppressing charge recombination are critically important to minimize the loss of absorbed photons and improve the device performance of polymer solar cells (PSCs). In ...this work, highly efficient PSCs are demonstrated by progressively improving the charge extraction and suppressing the charge recombination through the combination of side‐chain engineering of new nonfullerene acceptors (NFAs), adopting ternary blends, and introducing volatilizable solid additives. The 2D side chains on BTP‐Th induce a certain steric hindrance for molecular packing and phase separation, which is mitigated by fluorination of side chains on BTP‐FTh. Moreover, by introducing two highly crystalline molecules as the second acceptor and volatilizable solid additive, respectively, into the BTP‐FTh‐based host blend, the molecular crystallinity is significantly improved and the blend morphology is finely optimized. As expected, enhanced charge extraction and suppressed charge recombination are progressively realized, contributing to the largely improved fill factor (FF) of the resultant devices. Accompanied by the enhanced open‐circuit voltage (Voc) and short‐circuit current density (Jsc), a record high power conversion efficiency (PCE) of 19.05% is realized finally.
The progressive improvement of charge extraction and suppression of charge recombination by side‐chain engineering of Y‐series nonfullerene acceptors (NFAs), employing a ternary blend and introducing a volatilizable solid additive, fine‐tunes the electronic properties of the NFAs and optimizes the morphology of the active layer and contributes to a record power conversion efficiency of 19.05% for single‐junction polymer solar cells.
A side‐chain conjugation strategy in the design of nonfullerene electron acceptors is proposed, with the design and synthesis of a side‐chain‐conjugated acceptor (ITIC2) based on a ...4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)benzo1,2‐b:4,5‐b′di(cyclopenta‐dithiophene) electron‐donating core and 1,1‐dicyanomethylene‐3‐indanone electron‐withdrawing end groups. ITIC2 with the conjugated side chains exhibits an absorption peak at 714 nm, which redshifts 12 nm relative to ITIC1. The absorption extinction coefficient of ITIC2 is 2.7 × 105m−1 cm−1, higher than that of ITIC1 (1.5 × 105m−1 cm−1). ITIC2 exhibits slightly higher highest occupied molecular orbital (HOMO) (−5.43 eV) and lowest unoccupied molecular orbital (LUMO) (−3.80 eV) energy levels relative to ITIC1 (HOMO: −5.48 eV; LUMO: −3.84 eV), and higher electron mobility (1.3 × 10−3 cm2 V−1 s−1) than that of ITIC1 (9.6 × 10−4 cm2 V−1 s−1). The power conversion efficiency of ITIC2‐based organic solar cells is 11.0%, much higher than that of ITIC1‐based control devices (8.54%). Our results demonstrate that side‐chain conjugation can tune energy levels, enhance absorption, and electron mobility, and finally enhance photovoltaic performance of nonfullerene acceptors.
A side‐chain conjugation strategy in the design of nonfullerene electron acceptors is proposed and the first example of a side‐chain‐conjugated fused‐ring electron acceptor is presented. Polymer solar cells based on side‐chain‐conjugated ITIC2 show a champion power conversion efficiency of 11.0%, much higher than its counterpart ITIC1‐based devices (8.54%).
Bioelectrochemical reactions using whole‐cell biocatalysts are promising carbon‐neutral approaches because of their easy operation, low cost, and sustainability. Bidirectional (outward or inward) ...electron transfer via exoelectrogens plays the main role in driving bioelectrochemical reactions. However, the low electron transfer efficiency seriously inhibits bioelectrochemical reaction kinetics. Here, a three dimensional and artificial nanoparticles‐constituent inverse opal‐indium tin oxide (IO‐ITO) electrode is fabricated and employed to connect with exoelectrogens (Shewanella loihica PV‐4). The above electrode collected 128‐fold higher cell density and exhibited a maximum current output approaching 1.5 mA cm−2 within 24 h at anode mode. By changing the IO‐ITO electrode to cathode mode, the exoelectrogens exhibited the attractive ability of extracellular electron uptake to reduce fumarate and 16 times higher reverse current than the commercial carbon electrode. Notably, Fe‐containing oxide nanoparticles are biologically synthesized at both sides of the outer cell membrane and probably contributed to direct electron transfer with the transmembrane c‐type cytochromes. Owing to the efficient electron exchange via artificial and biosynthetic nanoparticles, bioelectrochemical CO2 reduction is also realized at the cathode. This work not only explored the possibility of augmenting bidirectional electron transfer but also provided a new strategy to boost bioelectrochemical reactions by introducing biohybrid nanoparticles.
A 3D, honeycomb‐like, and nanoparticles‐constituent inverse opal‐indium tin oxide electrode stimulated highly electroactive biofilm formation of Shewanella loihica PV‐4. Artificial ITO nanoparticle electrodes and biosynthetic FeOx nanoparticles on cell surfaces largely boosted bidirectional electron transfer. It also assisted efficient bioelectrochemical reactions, such as bioelectricity production in anode mode and fumarate/CO2 bio‐reduction in cathode mode.
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