KRAS was recently identified to be potentially druggable by allele-specific covalent targeting of Cys-12 in vicinity to an inducible allosteric switch II pocket (S-IIP). Success of this approach requires active cycling of KRAS between its active-GTP and inactive-GDP conformations as accessibility of the S-IIP is restricted only to the GDP-bound state. This strategy proved feasible for inhibiting mutant KRAS in vitro; however, it is uncertain whether this approach would translate to in vivo. Here, we describe structure-based design and identification of ARS-1620, a covalent compound with high potency and selectivity for KRAS. ARS-1620 achieves rapid and sustained in vivo target occupancy to induce tumor regression. We use ARS-1620 to dissect oncogenic KRAS dependency and demonstrate that monolayer culture formats significantly underestimate KRAS dependency in vivo. This study provides in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRAS-specific inhibitors with promising therapeutic potential.

Fruits are the defining feature of angiosperms, likely have contributed to angiosperm successes by protecting and dispersing seeds, and provide foods to humans and other animals, with many morphological types and important ecological and agricultural implications. Rosaceae is a family with ∼3000 species and an extraordinary spectrum of distinct fruits, including fleshy peach, apple, and strawberry prized by their consumers, as well as dry achenetum and follicetum with features facilitating seed dispersal, excellent for studying fruit evolution. To address Rosaceae fruit evolution and other questions, we generated 125 new transcriptomic and genomic datasets and identified hundreds of nuclear genes to reconstruct a well-resolved Rosaceae phylogeny with highly supported monophyly of all subfamilies and tribes. Molecular clock analysis revealed an estimated age of ∼101.6 Ma for crown Rosaceae and divergence times of tribes and genera, providing a geological and climate context for fruit evolution. Phylogenomic analysis yielded strong evidence for numerous whole genome duplications (WGDs), supporting the hypothesis that the apple tribe had a WGD and revealing another one shared by fleshy fruit-bearing members of this tribe, with moderate support for WGDs in the peach tribe and other groups. Ancestral character reconstruction for fruit types supports independent origins of fleshy fruits from dry-fruit ancestors, including the evolution of drupes (e.g., peach) and pomes (e.g., apple) from follicetum, and drupetum (raspberry and blackberry) from achenetum. We propose that WGDs and environmental factors, including animals, contributed to the evolution of the many fruits in Rosaceae, which provide a foundation for understanding fruit evolution.

Chemical vapour deposition of two-dimensional materials typically involves the conversion of vapour precursors to solid products in a vapour-solid-solid mode. Here, we report the vapour-liquid-solid growth of monolayer MoS, yielding highly crystalline ribbons with a width of few tens to thousands of nanometres. This vapour-liquid-solid growth is triggered by the reaction between MoO and NaCl, which results in the formation of molten Na-Mo-O droplets. These droplets mediate the growth of MoS ribbons in the 'crawling mode' when saturated with sulfur. The locally well-defined orientations of the ribbons reveal the regular horizontal motion of the droplets during growth. Using atomic-resolution scanning transmission electron microscopy and second harmonic generation microscopy, we show that the ribbons are grown homoepitaxially on monolayer MoS with predominantly 2H- or 3R-type stacking. Our findings highlight the prospects for the controlled growth of atomically thin nanostructure arrays for nanoelectronic devices and the development of unique mixed-dimensional structures.

Vertically aligned carbon nanotubes (VACNTs) possess the advantages of a high degree of order, good controllability, and easy manipulation. Thus, their synthesis, properties, and potential for applications have been intensively investigated. [1][2][3][4][5] VACNTs are usually grown by chemical vapor deposition (CVD) on substrates with pre-deposited catalysts. Due to the rigorous CVD synthesis conditions, substrates employed for VACNT growth should be thermally and chemically stable materials, such as SiO 2 /Si, Al 2 O 3 , or quartz. A problem thus arising is that these substrates are usually insulators, which hampers the direct application of VACNTs in those areas that require desirable integrated electrical and thermal conductivities. [ 6 ] For example, a mismatching problem often emerges when assembling devices based on VACNTs due to the rigidity and poor conductivity of the substrates. To solve this problem, some researchers have developed multiform but complicated methods to transfer VACNTs from the insulating substrates to conducting substrates by post-synthesis processing, which facilitates the application of VACNTs in some electronic devices, such as fi eld emitters. [ 7,8 ] On the other hand, Tatsuki et al. reported direct growth of VACNTs on Ni-based alloy foils. [ 9 ] Although excellent fi eld emission homogeneity was demonstrated, the 30 nm thick alumina buffer layer deposited between the metal substrate and catalyst fi lm weakens the electrical contact and mechanical adhesion between the VACNTs and the metal substrate. The incompatible thermal expansion coeffi cients of alumina and metal may also lead to detaching of the VACNTs and the alumina buffer layer from the metal substrate.Graphene is a newly discovered 2D carbon material with excellent conductivity, mechanical properties, [ 10,11 ] and more importantly, compatibility with CNTs. Therefore, graphene can be an ideal substrate for VACNT growth. Recently, Lee et al. demonstrated the growth of VACNTs on a ∼ 7 nm thick reduced graphene fi lm supported by silicon wafer. The VACNT/ graphene hybrid fi lm infi ltrated with a poly(dimethyl siloxane) (PDMS) elastomer displayed good mechanical properties, electrical conductivity, and fi eld emission performance. [ 12 ] Nitrogendoped VACNTs grown on mechanically compliant graphene fi lm for a fl exible fi eld emitter were also demonstrated by Lee et al. [ 13 ] Jeong et al. reported a flexible room temperature NO 2 gas sensor consisting of a VACNT/reduced graphene hybrid film supported by a polyimide substrate. [ 14 ] Paul et al. prepared a 3D pillared graphene nanostructure comprising graphene and aligned carbon nanotubes by a one-step CVD method. [ 15 ] Zhang et al. demonstrated desirable visible light photocatalytic performance for a 3D pillared CNT/reduced graphene oxide composite material. [ 16 ] Fan et al. prepared a 3D CNT/graphene sandwich with short CNT pillars ( ∼ 100 nm in length) grown between graphene layers or by ultrasonicating purifi ed, shortcut CNTs in a graphene oxide suspension followed b...