资源环境科技发展态势分析平台

Strain engineering is a powerful tool with which to enhance semiconductor device performance(1,2). Halide perovskites have shown great promise in device applications owing to their remarkable electronic and optoelectronic properties(3-5). Although applying strain to halide perovskites has been frequently attempted, including using hydrostatic pressurization(6-8), electrostriction(9), annealing(10-12), van der Waals force(13), thermal expansion mismatch(14), and heat-induced substrate phase transition(15), the controllable and device-compatible strain engineering of halide perovskites by chemical epitaxy remains a challenge, owing to the absence of suitable lattice-mismatched epitaxial substrates. Here we report the strained epitaxial growth of halide perovskite single-crystal thin films on lattice-mismatched halide perovskite substrates. We investigated strain engineering of a-formamidinium lead iodide (alpha-FAPbI(3)) using both experimental techniques and theoretical calculations. By tailoring the substrate composition-and therefore its lattice parameter-a compressive strain as high as 2.4 per cent is applied to the epitaxial alpha-FAPbI(3) thin film. We demonstrate that this strain effectively changes the crystal structure, reduces the bandgap and increases the hole mobility of alpha-FAPbI(3). Strained epitaxy is also shown to have a substantial stabilization effect on the alpha-FAPbI(3) phase owing to the synergistic effects of epitaxial stabilization and strain neutralization. As an example, strain engineering is applied to enhance the performance of an alpha-FAPbI(3)-based photodetector.

The cyclin-dependent kinase inhibitor CR8 acts as a molecular glue compound by inducing the formation of a complex between CDK12-cyclin K and DDB1, which results in the ubiquitination and degradation of cyclin K.

Molecular glue compounds induce protein-protein interactions that, in the context of a ubiquitin ligase, lead to protein degradation(1). Unlike traditional enzyme inhibitors, these molecular glue degraders act substoichiometrically to catalyse the rapid depletion of previously inaccessible targets(2). They are clinically effective and highly sought-after, but have thus far only been discovered serendipitously. Here, through systematically mining databases for correlations between the cytotoxicity of 4,518 clinical and preclinical small molecules and the expression levels of E3 ligase components across hundreds of human cancer cell lines(3-5), we identify CR8-a cyclin-dependent kinase (CDK) inhibitor(6)-as a compound that acts as a molecular glue degrader. The CDK-bound form of CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation. Our studies demonstrate that chemical alteration of surface-exposed moieties can confer gain-of-function glue properties to an inhibitor, and we propose this as a broader strategy through which target-binding molecules could be converted into molecular glues.

The structure of human diacylglycerol O-acyltransferase 1, a membrane protein that synthesizes triacylglycerides, is solved with cryo-electron microscopy, providing insight into its function and mechanism of enzymatic activity.

Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste(1-3). Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.

Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.