Heteromeric amino acid transporters (HATs) catalyze the transmembrane movement of amino acids, comprising two subunits, a heavy chain and a light chain, linked by a disulfide bridge. The b0,+AT (SLC7A9) is a representative light chain of HATs, forming heterodimer with rBAT, a heavy chain which mediates the membrane trafficking of b0,+AT. The b0,+AT-rBAT complex is an obligatory exchanger, which mediates the influx of cystine and cationic amino acids and the efflux of neutral amino acids in kidney and small intestine. Here, we report the cryo-EM structure of the human b0,+AT-rBAT complex alone and in complex with arginine substrate at resolution of 2.7 and 2.3 Å, respectively. The overall structure of b0,+AT-rBAT exists as a dimer of heterodimer consistent with the previous study. A ligand molecule is bound to the substrate binding pocket, near which an occluded pocket is identified, to which we found that it is important for substrate transport.

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Electromagnetic radiation (EMR) in the environment has increased sharply in recent decades. The effect of environmental EMR on living organisms remains poorly characterized. Here, we report the impact of wireless-range EMR on the sleep architecture of mouse. Prolonged exposure to 2.4-GHz EMR modulated by 100-Hz square pulses at a nonthermal output level results in markedly increased time of wakefulness in mice. These mice display corresponding decreased time of nonrapid eye movement (NREM) and rapid eye movement (REM). In contrast, prolonged exposure to unmodulated 2.4-GHz EMR at the same time-averaged output level has little impact on mouse sleep. These observations identify alteration of sleep architecture in mice as a specific physiological response to prolonged wireless-range EMR exposure.

Inhibition of γ-secretase activity represents a potential therapeutic strategy for Alzheimer’s disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of γ-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing γ-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 Å. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting γ-secretase.

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In the context of a new round of global scientific and technological revolution and industrial transformation, new enterprises with technological advantages and market prospects are the main force leading cutting-edge technology and disruptive technology. However, there are target differences and governance conflicts between venture investors and new enterprises, which are mainly reflected in whether to give priority to R&D and innovation strategies with high risk, long cycle and large investment. Then, is the enterprise development innovation-driven or still based on the past economic-orientated? Based on Python and STATa software, this paper conducts big data analysis on 2,756,910 samples of Chinese enterprises, and finds that the innovation-driven strategy of enterprises is still at the strategic level, and the tactical level is still dominated by economic scale.

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