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The ferroptosis suppressor protein FSP1 has a critical role in ferroptosis protection of tumours across multiple in vivo models and is linked to worse prognosis in human lung adenocarcinoma, suggesting its potential as a therapeutic target in lung cancer.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

It is becoming clear that heterogeneity in cancer cell cycles corresponds to variability of response to therapies targeting cyclin dependent kinases (CDKs). Here, the authors investigate CDK2-dependancy and response to CDK2 inhibition across different cancers, identifying markers of sensitivity and combinatorial therapeutic strategies.

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Electrophysiological, structural and biochemical studies on the bestrophin-2 anion channel reveal asymmetric permeability to glutamate and show that it forms a cooperative machinery in complex with glutamine synthetase for glutamate release.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A noise-resilient protocol implemented in a cavity resonator coupled to a qubit demonstrates that large nonlinear couplings are not a necessary requirement for the fast universal control and state preparation of engineered quantum systems.

Through a quantitative proteomics analysis, a cohort of proteins is identified that associate with autophagosomes, among them a new cargo receptor called NCOA4 that, in response to iron deprivation, targets ferritin to autophagosomes and thereby releases iron.

Bestrophin-1 (Best1) is an anion channel genetically linked to eye diseases. Here, the authors identify GAD65 and GAD67 as Best1 activators with distinctive functional influences and characterize Best1 as a γ-Aminobutyric acid (GABA) type A receptor.

Bestrophin channels are critical for physiology of the eye. Here, authors report cryo-EM structures of human bestrophins in various states at up to 1.8 Å resolution, revealing paralog-specific features that underlie molecular mechanisms of permeation.

Bestrophin anion channels are critical for the health of eyes. Here, authors identify multiple bestrophin activators including glutamate and γ-aminobutyric acid.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Mass cytometry can be used to scale up multiplexed serology testing, as shown for the simultaneous detection of antibody levels against multiple SARS-CoV-2 proteins in hundreds of serum samples.

Despite their intriguing photochemical activities, natural photoenzymes have not yet been repurposed for new-to-nature activities. Now, by leveraging the strongly oxidizing excited-state flavoquinone cofactor, fatty acid photodecarboxylases were engineered to catalyse unnatural decarboxylative radical cyclization with excellent chemo-, enantio- and diastereoselectivities.

Deep wounds with severe bleeding are a prominent cause of preventable deaths. Here, Shahriar et al. report a bicomponent nano- and microfiber aerogel that effectively halts bleeding in deep junctional wounds, outperforming FDA-approved hemostatic materials in a lethal swine model.

By affecting which form of a gene is expressed, alternative splicing is a major source of diversity in the nervous system. Here, the authors present an atlas of splice variants across neurons, and explore its impacts and mechanisms in the nematode nervous system.

Ion trapping in crystalline domains of electrochemical transistors can be used to create a device capable of both volatile and non-volatile operation.

Nonlinear light-matter coupling has applications in quantum technologies, for instance in quantum-non-demolition measurements, but its strength is typically limited. Here the authors demonstrate near-ultrastrong nonlinear light-matter coupling in a superconducting circuit with two transmons and a quarton coupler.

In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Circadian gene expression is fundamental to the circadian clock. Here the author showed post-translational processing is the dominant contributor to circadian nuclear proteome and Environmental Circadian Disruption re-writes the entire gene expression process from transcription to post-translation.

First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Glutaminase inhibition (GLSi) has promising activity against certain cancers. Here, the authors show that GLSi has no effect on multiple mouse models of pancreatic cancer and characterize the metabolic pathways activated in response to GLSi whose concomitant inhibition may have therapeutic utility.

The use of chimeric antigen receptor modified immune cell therapeutics has improved the treatment of a range of tumours. Here the authors explore a dual-target iPSC-derived NK cell product as a potential therapeutic for the treatment of multiple myeloma.

Electronic spin influences chemistry profoundly, but its role in surface chemistry is poorly established. Now the spin-dependent reaction probabilities of oxygen atoms with a graphite surface have been studied. Molecular dynamics simulations help elucidate the mechanism for spin-flipping, which is observed to occur with low probability in surface scattering experiments.

Pancreatic ductal adenocarcinoma (PDAC) cells display varying degrees of reliance on oncogenic KRAS. Here the authors show that KRAS-resistant PDAC cells maintain nucleotides synthesis through a KRAS-independent upregulation of the non-oxidative pentose phosphate pathway gene RPIA and that targeting nucleotide metabolism restore sensitivity to KRAS pathway inhibition.

Mutations in the gene HADHA result in mitochondrial tri-functional protein (MTP) deficiency and can result in sudden infant death syndrome for which there is no treatment. Here the authors show that the MTP deficient pathology in human cardiomyocytes leads to an abnormal cardiolipin pattern and suggests that cardiolipin affecting compounds may serve as a potential therapy.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Zika virus infection during pregnancy can result in birth defects, but underlying pathogenesis at the maternal-fetal interface is unclear. Here, the authors use non-invasive in vivo imaging of Zika-infected rhesus macaques and show that infection results in abnormal oxygen transport across the placenta.

Optimising antibody properties such as affinity can be detrimental to other key properties. Here the authors use machine learning to simplify the identification of antibodies with co-optimal levels of affinity and specificity for a clinical-stage antibody that displays high levels of on- and off-target binding.

Inelastic hydrogen atom scattering from surfaces provides a good benchmark for the validity of the Born–Oppenheimer approximation in surface chemistry. Now it has been shown that hydrogen atoms colliding with a semiconductor surface can efficiently excite electrons above the surface bandgap, representing a clear example of the failure of the approximation.

Metastasis remains difficult to treat owing to the heterogeneity of metastatic cancer cells and the various dynamic steps of the metastatic cascade. This Review discusses the design of nanomedicines for the specific treatment of metastasis.

Modeling collective dynamics in multi-agent systems is challenging due to the complexity of short and long-range interactions. Here, the authors develop hierarchical and equivariant graph neural networks that accurately predict local and global behaviors, outperforming traditional GNNs in forecasting collective motion in vortex clusters and microswimmers.

Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

The specific binding of N⁷-methylguanine cap analogues to the RNA methyltransferase VP39 was observed through X-ray crystallography, providing a prototypical structure for a complex between a protein and an mRNA 5′ cap.