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The success of targeting KRAS for cancer therapy is limited by resistance due to compensatory mechanism, making combinatorial approaches attractive. Here, the authors use a KRAS signature drug repurposing screen and identify the multityrosine kinase PKC inhibitor Midostaurin as synergistic with MEK and KRAS inhibitors in KRAS-mutated lung adenocarcinoma.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Highly bendable yet unstretchable ultrathin sheets can wrap a liquid droplet to form an optimal non-spherical shape that minimizes the unwrapped interfacial area, regardless of interfacial energies and the sheet’s mechanical properties.

Liver metastases reduce clinical and preclinical immune-checkpoint inhibitor efficacy through hepatic siphoning of circulating activated CD8⁺ T cells, but therapeutic benefit can be improved by combining immunotherapy with liver-directed radiotherapy.

Adaptive control to improve performance after making mistakes in a given task is known to involve prediction error signaling in the anterior cingulate cortex (ACC). The current study examines adaptive control in humans and rats by using comparable time-estimation tasks for each organism, and the authors show that low-frequency oscillations within the ACC in humans and the medial frontal cortex (MFC) in rats are correlated with adaptive behavioral control. They also show that these frontal oscillations are phase locked to the oscillation in the motor regions in the brain and that inactivation of the MFC in rats can disrupt both behavioral control and oscillatory coupling.

We present James Webb Space Telescope observations that detect the 3.3 μm polycyclic aromatic hydrocarbon feature in a galaxy observed less than 1.5 billion years after the Big Bang.

Theoretical models of colloids with directional and anisotropic interactions have predicted the existence of both liquids with vanishing density, and arrested networks at equilibrium — that is, not undergoing phase separation. Experimental evidence of empty liquids and equilibrium gels is now provided for Laponite, a synthetic clay. These observations further our understanding of anisotropic interactions in colloidal suspensions.

Viral gene expression can be regulated by chromatin methylation and demethylation. Thomas Kristie and his colleagues have identified a histone demethylase that is required to remove repressive methylation from the immediate early promoters of two α-herpesviruses. Monoamine oxidase inhibitors, which block this demethylase, prevented lytic replication and reactivation from latency.

Single-stranded DNA encoders containing polyadenine domains endow colloidal gold nanoparticles with programmable bond valence, orthogonality and reconfigurability, thus achieving post-synthetic control over colloidal structures.

Multiple sclerosis is a heterogeneous progressive disease. Here, the authors use an unsupervised machine learning algorithm to determine multiple sclerosis subtypes, progression, and response to potential therapeutic treatments based on neuroimaging data.

Understanding mesoscale structure and dynamics in organic mixed ionic–electronic conductors is crucial. Mesoscale strain kinetics and structural hysteresis have been studied, and they uncover the coupling between charge carrier dynamics and mesoscale order in organic mixed ionic–electronic conductors.

The TCR-peptide-MHC interface is composed of conserved and diverse regions, but the relative contributions of each in shaping T cell recognition remain unclear. Garcia and colleagues show consistent germline interactions between TCR and MHC, but enough flexibility in the TCR-peptide-MHC interface to allow adjustment for different peptides.

The impact of multiexcitonic through-space interactions in macromolecular architectures is poorly investigated. Here the authors use dendritic macromolecules to study the effect of interchromophore interactions on the dynamics of multiexciton generation and decay as a function of dendrimer generation.

Binary mixtures of 1D particles are rarely observed to cooperatively self-assemble into binary superlattices, as the particle types separate into phases. Here, the authors design a system that avoids phase separation, obtaining binary superlattices with different symmetries by simply tuning the particle diameter and mixture composition.

Zinc finger protein transcription factors are developed for the selective silencing of the mutant huntingtin gene in human neurons in vitro and multiple animal models of Huntington’s disease in vivo while preserving expression of the wild-type allele.

mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

The incorporation of the desirable properties of graphene into three-dimensional materials remains challenging. Here, the authors report the scalable self-assembly of graphene sheets into spongy materials with very low densities, and near-zero and largely strain-independent Poisson's ratios in all directions.

A new X-ray-based technique, X-ray photon correlation spectroscopy, is developed to directly measure magnetic noise. Its use is demonstrated for elemental chromium, an antiferromagnet that displays a nanometre-scale superstructure of spin- and charge-density. Fingerprints of a particular magnetic domain configuration are obtained, and after the temporal evolution of the patterns, magnetic domain walls advancing and retreating over micron distances are observed.

The application of resistive and phase-change memories in neuromorphic computation will require efficient methods to quantify device-to-device and switching variability. Here, the authors assess the impact of a broad range of device switching mechanisms using machine learning regression techniques.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Allele-specific expression at single-cell resolution can reveal stochastic and dynamic features of gene expression in greater detail. The authors propose scBASE, a soft zero-and-one inflated model that improves estimation of cellular allelic proportions by pooling information across cells.

The main limitation to the areal storage density of hard disk drives (HDDs) is the thickness of carbon overcoats protecting the disk media. Here, <2-nm-thick graphene overcoats with improved corrosion, wear and irradiation resistance are shown to meet the requirements for the realization of 4–10 Tb/in² HDDs with heat assisted magnetic recording.

Here, the authors provide a 3.4 Å resolution structure of mature Zika virus (ZIKV) and identify two lipid moieties, coordinated by hydrophobic residues of the M and E transmembrane helices and between two helices of E protein, that play an essential role in the ZIKV assembly pathway.

Ecosystem services provided by dung beetles are an underappreciated component of terrestrial ecosystems. Here, the authors report a standardized distributed experiment which shows that dung removal rate, a key ecosystem process in pastures, is greater under high beetle functional diversity regardless of grazing intensity.

The sodium-leak channel NALCN controls the resting membrane potentials of neurons. Here, the authors identified two subunits of NALCN, UNC80 and UNC79. Domains in UNC80, which are mutated in individuals with intellectual disability, interact to achieve the dendritic localization of NALCN complex.

The recovery of two circularized genomes of the Heimdallarchaeum species from hydrothermal vent enrichment cultures reveals that these Asgard archaea carry diverse mobile genetic elements, such as an integrative viral genome and aloposons. These mobile genetic elements contain several bacteria- and phage-derived genes, modulating the shuffling of information between bacteria and archaea, and potentially influencing eukaryogenesis.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

An mRNA vaccine platform to prevent HIV-1 infection generated broadly neutralizing antibodies in non-human primates and protected some animals from infection, raising hope that optimization of this approach might lead to an effective HIV vaccine.

UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.

The interface between the Li metal electrode and inorganic solid electrolyte is crucial for developing reliable all-solid-state Li batteries. Here, the authors show that the Li plating current density distinctly affects the chemistry and morphology of interphase components formed at the interface.

Genotoxic agents have been shown to activate the Wnt/β-catenin signaling but the underlying mechanism remains unclear. Here, the authors show that upon DNA damage, the deubiquitinase OTULIN activates Wnt/β-catenin signaling by inhibiting linear ubiquitination, K48-linked polyubiquitination, and proteasomal degradation of β-catenin.

A multicore analogue in-memory computing chip that is designed and fabricated in 14 nm complementary metal–oxide–semiconductor technology with backend-integrated phase-change memory can be used for deep neural network inference.

An aluminium–chalcogen battery operating with a molten-salt electrolyte composed of NaCl–KCl–AlCl₃ is presented, which allows rapid charging at up to 200C for hundreds of cycles, and is scalable, fire-resistant and low cost.