Search

To realize the practical applications of the next-generation lithium-metal batteries (LMBs), it is critical to developing high-areal-capacity lithium (Li) anodes with high reversibility and dendrite-free electrodeposition. Herein, we demonstrate a “dendrite-eating” strategy to enable high-areal-capacity LMBs by introducing silicon (Si) coating onto the polypropylene (PP) separator. The Si layer is found to be effective in stabilizing the Li electrodeposition and reduce the Li loss. The in-situ optical cell observation and electrochemical characterizations reveal that the “dendrite-eating” coating serves as both a Li absorbant to suppress (“eat”) the dendrites growth and a backup Li reservoir to replenish the Li loss. With this “dendrite-eating” separator, the Li consumption during cycling is reduced by 66%, and the cyclability and reversibility of the Li anodes are also significantly improved, leading to a prolonged stripping/plating lifetime for >1000 ​h and high Coulombic efficiency (CE) of >97.6% in carbonate electrolyte. Coupled with an industry-level high-loading LiFePO4 cathode (20.0 ​mg ​cm−2), a thin Si coating of only 0.2 ​mg ​cm−2 on the separator remarkably improves the full-cell cycling stability.

While thermal proteome profiling (TPP) shines in the field of drug target screening by analyzing the soluble fraction of the proteome samples treated at high temperature, the counterpart, the insoluble precipitate, has been overlooked for a long time. The analysis of the precipitate is hampered by the inefficient sample processing procedure. Herein, we propose a novel method, termed microparticle-assisted precipitation screening (MAPS), for drug target identification. The MAPS method exploits the principle that drug-bound proteins will be more resistant to thermal unfolding similar to the classic TPP method, but the process of protein precipitation is assisted by microparticles. Upon heating, proteins unfold and aggregate on the surface of the microparticles. The introduction of a microparticle simplifies the whole sample preparation workflow. The proteins that precipitate on the microparticles are subjected to washing, alkylation, and digestion. The whole sample preparation is processed conveniently on the surface of the microparticles without any transfer. With the assistance of microparticles, sample loss is minimized. The MAPS method is compatible with minute amounts of initial proteins. MAPS was applied to screen the targets of several well-studied drugs and the known target proteins were successfully identified with high confidence and specificity. To investigate the specificity of the method, MAPS was applied to screen the targets of the pan-kinase inhibitor, staurosporine, and 32 protein kinases (specificity of 80%) were identified using only 20 μg of initial proteins of each sample. MAPS is an unbiased robust method for drug target screening, filling the vacancy of stability-based target screening using a precipitate.

New electron-donating fused-ring cores based on tetrathienoacene were designed, with which new NIR-sensitive fused-ring electron acceptors, F8IC1 and F10IC1, were synthesized. Compared with the thieno[3,2-b]thiophene-based counterpart F6IC, F8IC1 and F10IC1 show heavily elevated HOMO and slightly elevated LUMO levels, bathochromic absorption spectra with reduced optical bandgaps, and enhanced electron mobilities. Paired with the polymer donor material PTB7-Th, the organic photovoltaic devices based on F8IC1 and F10IC1 show synchronous enhancement of open-circuit voltage, short-circuit current and fill factor. The single-junction cells based on F8IC1 and F10IC1 achieve efficiencies of 10.7% and 12.3%, respectively, surpassing those of the F6IC-based control cells (7.00%).

A fused heptacyclic electron acceptor, ITIC5, based on a benzodi(cyclopentadithiophene) core flanked by thiophene-fused termini, is designed, synthesized, and compared with its benzene-fused analogue, ITIC1. ITIC5 with thiophene-fused termini exhibits a narrower optical band gap, stronger and redshifted absorption, and higher electron mobility than ITIC1. The active layer consisting of a wide-bandgap polymer donor J71 and ITIC5 exhibits a smaller acceptor domain, stronger crystallinity, and higher and more balanced mobilities than its J71:ITIC1 counterpart, contributing to efficient exciton dissociation and charge transport. J71:ITIC5 based organic solar cells exhibit a high fill factor of 75.5% and a champion power conversion efficiency of 12.5%, a nearly 40% boost in efficiency with respect to the ITIC1-based control device, suggesting that the thiophene-fused end group has great potential for constructing high-performance fused-ring electron acceptors.

The process of protein precipitation can be used to decipher the interaction of ligand and protein. For example, the classic Thermal Proteome Profiling (TPP) method uses heating as the driving force for protein precipitation, to discover the drug target protein. Under heating or other denature forces, the target protein that binds with the drug compound will be more resistant to precipitation than the free protein. Similar to thermal stress, mechanical stress can also induce protein precipitation. Upon mechanical stress, protein will gradually precipitate along with protein conformational changes, which can be exploited for the study of the ligand-protein interaction. Herein, we proposed a Mechanical Stress Induced Protein Precipitation (MSIPP) method for drug target deconvolution. Its streamlined workflow allows in situ sample preparation on the surface of microparticles, from protein precipitation to digestion. The mechanical stress was generated by vortexing the slurry of protein solution and microparticle materials. The mechanical stress induced protein precipitate was captured by the microparticles, which guarantees the MSIPP method to be scalable and user-friendly. The MSIPP method was successfully applied to four drug compounds, Methotrexate, Raltitrexed, SHP099, Geldanamycin and a pan-inhibitor of protein kinases, Staurosporine. Besides, DHFR was demonstrated to be a target of Raltitrexed, which has not been revealed by any other modification-free drug target discovery method yet. Thus, MSIPP is a complementary method to other drug target screening methods.

Bone morphogenetic protein (BMP)-9 has been associated with insulin resistance and type 2 diabetes mellitus. However, methods for delivering exogenous BMP-9 genes in vivo are lacking. In this study, we developed a gene delivery system using polyethyleneimine (PEI)-based core-shell nanoparticles (PCNs) as gene delivery carriers, and investigated the effectiveness and safety for delivery of the shBMP-9 gene. PCNs possessed a well-defined core-shell nanostructure with hydrophobic polymer cores and dense PEI shells of uniform particle size and highly positively charged surfaces. In vitro evaluation suggested that PCNs had high loading capacity for exogenous genes and low cytotoxicity toward hepatocytes. The transfection efficiency of PCNs/pENTR-shBMP9 complexes was higher than that of commercial lipofectamine 2000/shBMP9. In vivo studies showed that PCNs/pENTR-shBMP9 transfection led to a significant decrease in hepatic BMP9 expression compared with pENTR-shBMP9 transfection. Under high fat diet (HFD) feeding, PCNs/pENTR-shBMP9 mice exhibited aggravated glucose and insulin tolerance. At a molecular level, PCNs/pENTR-shBMP9 mice displayed elevated PEPCK protein levels and lower levels of InsR and Akt phosphorylation than pENTR-shBMP9 mice. These results suggest that the biological effects of PCNs/pENTR-shBMP9 in vivo are much more effective than those of pENTR-shBMP9. Therefore, the polyethyleneimine (PEI)-based core-shell nanoparticle can be applied as promising nanocarriers for effective and safe gene delivery.