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The mechanism of action is through targeting the viral Mpro, which was supported by the thermal shift-binding assay and enzymatic fluorescence resonance energy transfer assay. We further showed that these four compounds have additive antiviral effect when combined with remdesivir. Altogether, these results suggest that boceprevir, calpain inhibitors II and XII, and GC-376 might be promising starting points for further development against existing human coronaviruses as well as future emerging CoVs.All-solution-processed multilayered white polymer light-emitting diodes (WPLEDs) are promising candidates for low-cost and large-area flexible full-color flat-panel displays and solid-state lighting. However, it is still challenging to improve their performance. In this work, based on an elegant strategy of orthogonal materials, the utilization of the cross-linked Ir3+ polymer film poly(NVK-co-[Ir(4-vb-PBI) 2 (acac)]- co -NVK) (NVK = N-vinyl-carbazole; 4-vb-HPBI = 1-(4-vinylbenzyl)-2-phenyl-1H-benzo[d]imidazole; and Hacac = acetylacetone) as the emitting layer (EML) between a hydrophilic polymer film poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate) (PEDOTPSS) as the hole injection layer (HIL) and a hydrophobic polymer film poly(vinyl-PBD) (vinyl-PBD = 2-(4-(tert-butyl)phenyl)-5-(4'-vinyl-[1,1'-biphenyl]-4-yl)-2,5-dihydro-1,3,4-oxadiazole) as the electron transport layer (ETL) led to the successful fabrication of reliable all-solution-processed multilayered WPLEDs. The device exhibits a ηCEMax of 18.19 cd/A, a ηPEMax of 8.16 lm/W, and a ηEQEMax of 9.32% with stable white light (Commission International De L'Eclairage (CIE) coordinates x = 0.269-0.283, y = 0.317-0.330; corrected color temperatures (CCTs) of 7237-8199 K, and CRIs (color rendering indices) of 63-72) under a wide applied-voltage range. Its high performance, especially with record efficiencies among those of reported all-solution-processed WPLEDs, renders cross-linked Ir3+ polymers a new platform to all-solution-processed multilayered WPLEDs.Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method to synthesis of β-alkylketoesters using the cross-coupling between aliphatic amides and esters. Meanwhile, gram-scale secondary and primary amides reacted via in situ generated activated tertiary amides and exhibited good reactivity when coupled with esters.The purpose of this study was to determine the neuroprotective effect and mechanism of walnut protein hydrolysates (WPH) against memory deficits induced by scopolamine in mice and further to validate the potent neuroprotective peptides identified by integrated approaches of in silico analysis and peptidomics in scopolamine-induced zebrafish. Results showed that a remarkable amelioration on behavioral performance was observed for oral administration of WPH, and disorders of cholinergic system and oxidative stress were normalized in the brains of mice also. Unfortunately, no obvious inflammatory response and anti-inflammatory effect were observed. Additionally, WPH significantly upregulated the expressions of antioxidant defense-related protein (Nrf2) and neurotrophic-related protein (BDNF and CREB). Furthermore, 20 peptides with relatively higher abundance and PeptideRanker scores were predicted by docking to AchE and Keap1. Among them, FY and SGFDAE with the highest binding affinities, -9.8 and -8.0 kcal/mol, were considered as the promising AchE and Keap1 inhibitors, respectively. They were further validated to have neuroprotective capacity in scopolamine-induced zebrafish, indicating that peptidomics and in silico prediction might be the effective approaches to screen neuroprotective peptides.Small molecules that independently perform natural channel-like functions show greatly potential in the treatment of human diseases. Taking advantage of aromatic helical scaffolds, we develop a kind of foldamer-based ion channels with lumen size varying from 3.8 to 2.3 Å through a sequence substitution strategy. Our results clearly elucidate the importance of channel size in ion transport selectivity in molecular detail, eventually leading to the discoveries of the best artificial K+ channel by far and a rare sodium-preferential channel as well. High K+ selectivity and transport activity together make foldamers promising in therapeutic applications.Spiroaxillarone A, a novel and unique spirocyclic dinaphthalene natural product with significant antimalarial activity, was regioselectively synthesized from tetrahydrocurcumin in five steps with an overall 10% yield. Key features of the synthesis involved an oxidized free radical cycloaddition to build the spiro ring central skeleton and an oxidized dehydrogenation to introduce two double bonds via enol silicon ether from diketones.An animal mammary bioreactor is regarded as an excellent biological system which is applied to produce large-scale recombinant proteins in milk. However, there are no effective methods to produce a large amount of some pharmaceutical proteins, such as human follicle-stimulating hormone (FSH), by large animal mammary gland bioreactors due to the fact that accumulation of excessive bioactive FSH might cause serious diseases in animals. Larotrectinib Here, we report a novel strategy of preparing recombinant human FSH (rhFSH) from goat mammary glands, which could avoid the accumulation of bioactive FSH in goats. First, the single inactive FSHα and FSHβ subunits expressed in goat mammary epithelial cells and goat mammary glands were performed to reassemble in vitro and were found to self-assemble into a complete heterodimer rhFSH at 4 °C and pH 7.4. Further, a cyclic adenosine monophosphate (cAMP) induction assay showed that the cAMP levels in cell lysate of HEK 293/FSHR cells were increased by about 8-fold in reassembled rhFSH groups than that in the control group (P 0.05). In addition, the increasing dose of reassembled rhFSH significantly promoted ovulation of mouse and ovary weight gain of Sprague Dawley rat compared with the control groups and maximum values were up to 3-fold (P less then 0.01) and 2.8-fold (P less then 0.01), respectively. The reassembled rhFSH showed a similar effect to Gonal-F in inducing expression of FSH target genes in vivo and activating the PI3K pathway in granulosa cells. Our study developed a novel method to produce rhFSH and provided the basis for preparing FSH by the goat mammary gland bioreactor with less health problems on the producing animals.
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