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From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Using intracranial electroencephalography from patients with epilepsy during spatial attention tasks, this study shows that high-frequency bursts facilitate fast communications in brain networks and support attentional information routing.

Creating shape morphing structures with stiff and tough time-responsive materials is a challenge for 4D printing. Here, the authors address this challenge showing a multi-material printing method that combines a stiff synthetic muscle with a stretchable adhesive to form actuators that can generate large specific force and detect and tolerate damage.

A strategy to control HIV-1 infection is to stably repress HIV-1 and induce “deep latency”. Here the authors show that a recombinant anti-HIV-1-1 protein can be packaged as mRNA into exosomes and delivered systemically to repress HIV-1-1 within the context of virus infected mice and achieve long term silencing of HIV-1-1 expression.

The pathogenic avian flu H5N1 virus remains stable in raw milk and throughout the cheese-making process, but contaminated cheese fed to ferrets did not lead to infection, whereas raw milk did.

TEAD transcription factors are critical effectors and druggable sites of the Hippo pathway in cancer, however, the development of small molecule inhibitors and degraders remains underexplored. Here, the authors identify and characterize bifunctional IAP-based degraders targeting TEAD1 via a lipid pocket and recruit different members of the inhibitor of apoptosis proteins (IAPs) family, offering a comprehensive toolkit for structural, biophysical and cellular profiling.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

In this study, authors introduce small molecular taxon-specific markers for bacterial detection directly in complex matrices using MS-based (spatial) metabolomics. This method has the potential to advance microbiological diagnostics and host-microbe research.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

Adherens junctions mediate force transmission and connect the cytoskeleton of adjacent cells. This study demonstrates that force transmission can be achieved through direct and functional β-catenin/vinculin interaction in the absence of α-catenin.

Computer vision coupled with gene expression shed light on the collective organizational patterning of glioma stem cells, which correlates with glioma stem cell phenotypes

Efforts in predicting crystal structures from first principles have mainly focused on the bulk materials. A general approach based on a genetic algorithm is now proposed to simulate grain boundaries and heterophase interfaces in multicomponent systems. The efficiency of the approach is demonstrated in the case of grain boundaries in SrTiO₃.

The discovery of superconductivity in the infinite-layer nickelates reignites an interest in the nickelates as cuprate analogues. Here, the authors investigate the role of epitaxial strain in the synthesis of the n=3 layered nickelate, Nd₄Ni₃O₈.

Beck et al. conducted single-cell and spatial profiling of embryonal tumors with multilayered rosettes, finding that malignant cellular hierarchies are driven by developmental programs and specific members of the chromosome 19 microRNA cluster.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Analysis of ancient proteins suggests that Early Bronze Age dairying and horse domestication catalysed eastern Yamnaya migrations.

A study reports a quantum gravity gradient sensor with a design that eliminates the need for long measurement times, and demonstrates the detection of an underground tunnel in an urban environment.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

A technique to detect the release of N-terminal fragments of Drosophila adhesion G-protein-coupled receptors (aGPCRs) provides insight into the dissociation of aGPCRs, and shows that receptor autoproteolysis enables non-cell-autonomous activity of aGPCRs in the brain.

The origin and dispersal of the chicken across Eurasia is unclear. Here, the authors examine eggshell fragments from southern Central Asia with paleoproteomics to identify chicken eggshells, suggesting that chickens may have been an important dietary component as early as 400BCE.

Innovative substrate engineering is necessary to improve the quality of CVD-synthesized graphene. Here the authors demonstrate in situfabrication of an eutectic Pt-Si alloy that forms a wetting liquid surface on polycrystalline Pt foils, allowing millimetre-sized graphene crystals to grow in minutes.

Diacylglycerol kinase is a small bacterial membrane-bound trimer that catalyses diacylglycerol conversion to phosphatidic acid. Here, the authors solve the crystal structure of the kinase bound to a lipid substrate and an ATP analogue, and show that the active site arose through convergent evolution.

There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.

The Na⁺-pumping NADH-ubiquinone oxidoreductase (Na⁺-NQR) is a unique respiratory enzyme found in many pathogenic bacteria. Here, the authors present high-resolution cryo-EM structures of Na⁺-NQR from V. cholerae with or without a bound inhibitor.

During a photoinduced phase transition, electronic rearrangements are usually faster than lattice ones. Time-resolved measurements now show that the insulator-to-metal transition in a thin-film Mott insulator is preceded by lattice reconfiguration.

Impaired awareness of hypoglycaemia (IAH) is a risk for severe hypoglycaemia in insulin treatment of type 1 diabetes (T1D). Here the authors report that a group programme focussing on changing cognitive barriers to avoiding hypoglycaemia (HARPdoc) does not reduce severe hypoglycaemia more than a programme focussing on behaviours (BGAT) in a randomized control trial in adults with T1D and treatment-resistant IAH and severe hypoglycaemia.

A potent and selective inhibitor of KRAS^G12D, the most common mutant form of the KRAS oncoprotein, has anti-tumor efficacy in multiple pre-clinical cancer models, opening the possibility to therapeutically target this highly prevalent oncogenic driver.

Here the authors show mutants of isocitrate dehydrogenase 1 (IDH1), an enzyme implicated in various cancers, have distinct catalytic and structural features that drive their ability to generate an oncometabolite.

In a large multicentric study of patients with advanced NSCLC undergoing anti-PD-1 therapy, the relative abundance of intestinal Akkermansia spp. was shown to associate with changes in the gut microbiome ecosystem and clinical outcomes.

A large integrated genome and transcriptome analysis of colorectal cancer identifies prognostic mutations and expression subtypes.

Papsdorf et al. show that mono-unsaturated fatty acids extend lifespan of C. elegans through induction of peroxisomes and lipid droplets in fat tissues and of a lipid signature predictive of decreased lipid oxidation.

Metabolomics is improved by using a reference library of both known and unknown molecules.

The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between open and closed conformations. Disulfide bonds are engineered into the spike ectodomain to lock the RBD in the closed state, leading to a construct with high thermostability.

Spatiotemporal transcriptomes during multicellular development of Bacillus subtilis swarms reveal supra-generational cooperation.

Consuming the milk of other species is a unique adaptation of Homo sapiens. Here, the authors carry out proteomic analysis of dental calculus of 41 ancient individuals from Sudan and Kenya, indicating milk consumption occurred as soon as herding spread into eastern Africa.

Greter and colleagues identify a population of CD11c⁺F4/80⁺CD64⁺MHCII⁺CX3CR1⁺ macrophages in the mouse mammary gland that is induced by lactation and resembles several subsets of macrophages detected in human milk.

Ancient proteins in human dental calculus from sites across Mongolia spanning 5,000 years suggest dairy consumption on the eastern Eurasian steppe by circa 3000 bc, and the later emergence of horse milking at circa 1200 bc, concurrent with the first evidence for horse riding.

The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).

Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4⁺ T cell lineage integrity by repressing Runx-CBFβ complexes in T_H1 cells but not in T_H2 cells.

Chemotherapeutic antifolates, such as methotrexate (MTX), impair cancer cell proliferation by inhibiting nucleotide synthesis. Here, the authors show that MTX sustains an autarkic mitochondrial one-carbon metabolism leading to serine synthesis to promote cancer cell migration and metastasis.

In large qubit registers, long coherence times and individual qubit control are difficult to achieve at the same time. Here, the authors assemble a 2D register of qubits in an array of fermionic alkaline-earth atoms, where tailored pulses can be applied to subsets of individual qubits in parallel.

Bifidobacterium species associated with breastfeeding can convert aromatic amino acids into their respective aromatic lactic acids via a previously uncharacterized aromatic lactate dehydrogenase, which may impact immune function in infants.

The mechanosensitive ion channel PIEZO1 senses shear stress induced by collagen-fibre sliding in tendons, regulates their stiffness and influences jumping performance.

The circadian clock can affect pathogen replication, but underlying molecular mechanisms are unclear. Here the authors demonstrate that the circadian components BMAL1 and REV-ERBα affect entry of hepatitis C virus (HCV) into hepatocytes and genome replication of HCV and related flaviviruses dengue and zika.

Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediates multidrug resistance, but its natural function remains unclear. Here, Shafik et al. show that PfCRT transports host-derived peptides of 4-11 residues but not other ions or metabolites, and that drug-resistance-conferring PfCRT mutants have reduced peptide transport.

Maintenance and quality control of the mitochondrial respiratory chain complexes responsible for bulk energy production are unclear. Here, the authors show that the mitochondrial protease ClpXP is required for the rapid turnover of the core N-module of respiratory complex I, which happens independently of other modules in the complex.

Circadian clocks regulate physiological and behavioural rhythms. Here, the authors show that the stiffness of the extracellular environment regulates circadian clocks in murine breast epithelium via Rho signalling, and explain how extracellular matrix stiffening in aging affects circadian rhythm, with implication in disease.