Turning to improve performances under industrial requirements may be more meaningful for research itself.

Lysine acetylation in proteins is a dynamic and reversible PTM and plays an important role in diverse cellular processes. In this study, using lysine-acetylation (Kac) peptide enrichment coupled with nano HPLC/MS/MS, we initially identified the acetylome in the silkworms. Overall, a total of 342 acetylated proteins with 667 Kac sites were identified in silkworm. Sequence motifs analysis around Kac sites revealed an enrichment of Y, F, and H in the +1 position, and F was also enriched in the +2 and -2 positions, indicating the presences of preferred amino acids around Kac sites in the silkworm. Functional analysis showed the acetylated proteins were primarily involved in some specific biological processes. Furthermore, lots of nutrient-storage proteins, such as apolipophorin, vitellogenin, storage proteins, and 30 K proteins, were highly acetylated, indicating lysine acetylation may represent a common regulatory mechanism of nutrient utilization in the silkworm. Interestingly, Ser2 proteins, the coating proteins of larval silk, were found to contain many Kac sites, suggesting lysine acetylation may be involved in the regulation of larval silk synthesis. This study is the first to identify the acetylome in a lepidoptera insect, and expands greatly the catalog of lysine acetylation substrates and sites in insects.

Using graphene oxide and a cobalt salt as precursor, a three-dimensional graphene aerogel with embedded Co3 O4 nanoparticles (3D Co3 O4 -RGO aerogel) is prepared by means of a solvothermal approach and subsequent freeze-drying and thermal reduction. The obtained 3D Co3 O4 -RGO aerogel has a high specific capacitance of 660 F g(-1) at 0.5 A g(-1) and a high rate capability of 65.1 % retention at 50 A g(-1) in a three-electrode system. Furthermore, the material is used as cathode to fabricate an asymmetric supercapacitor utilizing a hierarchical porous carbon (HPC) as anode and 6 M KOH aqueous solution as electrolyte. In a voltage range of 0.0 to 1.5 V, the device exhibits a high energy density of 40.65 Wh kg(-1) and a power density of 340 W kg(-1) and shows a high cycling stability (92.92 % capacitance retention after 2000 cycles). After charging for only 30 s, three CR2032 coin-type asymmetric supercapacitors in series can drive a light-emitting-diode (LED) bulb brightly for 30 min, which remains effective even after 1 h.

Herein we describe the design and synthesis of a series of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) for Alzheimer's disease (AD) that achieve good alignment of potency, metabolic stability, and low MDR efflux ratios, while also maintaining favorable physicochemical properties. Specifically, incorporation of fluorine enabled design of metabolically less liable lipophilic alkyl substituents to increase potency without compromising the sp(3)-character. The lead compound 21 (PF-06442609) displayed a favorable rodent pharmacokinetic profile, and robust reductions of brain Aβ42 and Aβ40 were observed in a guinea pig time-course experiment.

Herein we describe the design and synthesis of a novel series of γ-secretase modulators (GSMs) that incorporates a pyridopiperazine-1,6-dione ring system. To align improved potency with favorable ADME and in vitro safety, we applied prospective physicochemical property-driven design coupled with parallel medicinal chemistry techniques to arrive at a novel series containing a conformationally restricted core. Lead compound 51 exhibited good in vitro potency and ADME, which translated into a favorable in vivo pharmacokinetic profile. Furthermore, robust reduction of brain Aβ42 was observed in guinea pig at 30 mg/kg dosed orally. Through chemical biology efforts involving the design and synthesis of a clickable photoreactive probe, we demonstrated specific labeling of the presenilin N-terminal fragment (PS1-NTF) within the γ-secretase complex, thus gaining insight into the binding site of this series of GSMs.