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The combination of computational design, laboratory-based screening and biophysical validation enables the de novo generation of variable heavy-chain antibody fragments and antibodies that precisely target chosen disease-related molecules.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.   

By using proximity labeling, this study uncovers EFCAB5 as a sperm-specific protein associated with CFAP91 in sperm tails, revealing its crucial role in regulating sperm motility and offering insights into the molecular basis of male infertility.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.

Asymmetric hydrophosphorylation of unsaturated compounds is a straightforward and atom-economic approach to obtaining chiral organophosphorus compounds. Herein, the authors describe a Pd-catalzyed ligand controlled regiodivergent and enantioselective hydrophosphorylation of styrenes.

Layered crystal structures often exhibit twinning, planar disorder, or polytypes due to stacking variations. Here, the authors use multi-dimensional electron diffraction to uncover nanoscale disorder in xanthine, identifying a new polymorph and visualizing interfaces, suggesting such disorder may be prevalent in layered organic molecular crystals.

The membrane attack complex is a heteromeric assembly of complement proteins where multiple copies of C9 are recruited by the C5b678 complex to form lytic pores in pathogen membranes. Here the authors present the structure of a soluble pore-like form of the C9 component that reveals details of the oligomerization interfaces.

Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Epidemiological estimates from wastewater are not biased by testing rates but may be subject to other biases. Here, the authors investigate the impact of variable virus shedding profiles for different SARS-CoV-2 variants on estimates of their selection advantage.

GenomePAM compares activities and fidelities among different Cas nucleases on thousands of match and mismatch sites across the genome using a single gRNA.

China ended its ‘zero-COVID’ policy in late 2022, but the public health impacts of the rapid removal of restrictions are not known. Here, the authors use mathematical modelling combined with survey data and estimate that at least 90% of the population became infected by the end of December 2022.

In this target trial emulation study, the authors evaluate effectiveness of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron infection and show reduced risks of 28 day all-cause mortality or hospitalization associated with the treatment.

Quasicrystals promise exciting technological advances in optical devices, but their formation mechanism is yet not fully understood. Here, the authors describe a two-dimensional dodecagonal fullerene quasicrystal, forming on a Pt₃Ti(111)-surface due to the complex adsorption-energy landscape.

Assessment of PD-1 and PD-L1 expression can be predictive of immunotherapy response in lung cancer. Here the authors assess the clinical toxicity, safety and quality of non-invasive imaging of PD-1 and PD-L1 expression in 13 patients with advanced lung cancer prior to treatment with immunotherapy and show it correlates with response.

Estimates of the monetary costs of invasive species have been hampered by data gaps. These authors use documented costs for 162 species to interpolate costs of those species for countries previously lacking data and derive global costs 1,646% higher than previous estimates.

A single-cell resolution image-based genome-wide CRISPR screen, analysed with deep learning and random forest models, identified host factors regulating Ebola virus infection at distinct stages in the viral life cycle.

Antivirals are now available for treating COVID-19 but must be used early in the course of infection to be effective. Here, the authors use mathematical modelling to assess the potential public health impacts of antiviral use considering different levels of testing and country sociodemographic characteristics.

The ability to selectively break a chemical bond in a molecule is indispensable to chemical synthesis. Here, the authors show that a hundred-fold bond selectivity can be obtained in electron-induced surface reaction due simply to different bond alignments at the surface.

In a large multinational cohort study, maternal, gestational or pregestational diabetes was associated with only a small-to-moderate risk of ADHD in offspring, contrary to previous estimates that showed stronger effect sizes, attributing the differences in findings to confounding by shared genetic and familial factors.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Hong Kong has used an elimination strategy to control SARS-CoV-2 with stringent measures including traveller quarantine. Here, the authors show that the majority of community-acquired cases until January 2021 resulted from three importations, and that increased transmission followed prolonged periods of restrictions, likely due to adherence fatigue.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

Gene transfer agents (GTAs) are ‘domesticated’ bacteriophages that can transfer any genes between bacteria. Here, Paul Fogg identifies a protein that directly regulates transcription of GTA genes and whose expression is in turn controlled by a global cell-cycle regulator and a quorum-sensing regulator.

There are currently a lack of tools to detect heterogeneity in 3D cultures. Here the authors report Traject3d as a framework to identify heterogeneous states in 3D culture and to understand how these give rise to distinct phenotypes using label-free multi-day time-lapse imaging.

The authors develop a supervised and unsupervised learning algorithm Signature. Machine learning and network model analysis of Hi-C datasets across 62 2n genomes suggest that inter-chromosomal contacts demarcate genome topology along a spatial gradient of genome activity.

The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch.