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Recovering hydrocarbons from oil and gas wells results in highly saline wastewater, also known as flowback and produced water. The introduction of two parameters to estimate the environmental impact of these by-products, relative to energy produced, provides an important tool for assessing the risks associated with the planning and use of wells.

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.

Mulholland et al. identify progenitor exhausted T cells, expressing intermediate levels of PD-1 (PD-1^int), as a prominent source of pro-inflammatory cytokines in the murine atherosclerotic aorta and potential cellular targets driving checkpoint inhibition-elicited pro-atherosclerotic immune responses. They further demonstrate elevated levels of circulating PD-1-expressing T cells in individuals with subclinical cardiovascular disease.

The antibiotic polymyxin B requires bacterial metabolic activity to cause sufficient damage to the outer membrane to access the inner membrane, which it permeabilizes via an energy-independent mechanism to kill the cell.

The ability of individual ions trapped in separate potential wells to simulate spin–spin interactions is demonstrated by tuning the Coulomb interaction between two ions, independently controlling their local wells and entangling their internal states with a fidelity of approximately 0.82.

In a randomized, placebo-controlled, stepwise dose-escalation phase 1 trial evaluating a conjugate vaccine against both typhoid and invasive non-typhoidal Salmonella infections, the vaccine was found to be safe and immunogenic in healthy adults.

HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

Here the authors show that MRAP2 tunes the melanocortin-4 receptor by boosting its G-protein signaling while limiting β-arrestin2 interaction and destabilizing receptor oligomers, shaping appetite regulation.

Monoclonal antibodies targeting the conserved neuraminidase catalytic site mimic sialic acid and use coordinated water molecules to inhibit diverse influenza A and B viruses, including H5N1, providing broad prophylactic protection in mice.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

This study provides evidence that agricultural irrigation artificially recharges the groundwater in the Po Plain, highlighting the importance of irrigation inefficiencies for groundwater recharge.

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

Two-qubit operations exceeding 99% fidelity have been demonstrated by silicon devices made with standard semiconductor tooling in a 300-mm foundry environment.

Structural and functional characterization of the β-barrel assembly machinery complex in Bacteroidota reveals a distinct, seven-component complex with a large extracellular domain that may enable β-barrel–surface lipoprotein complex assembly.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

Plant-parasitic nematodes have the potential to destroy crops globally, and limited options for managing nematode infestation are available. Here, the authors report the 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes.

Single-cell chromatin accessibility is a promising means to identify regulatory programs in mixtures of cells. Here the authors describe µ-ATAC-seq, a low-cost method that can generate thousands of accessibility profiles per day.

The full potential of tunable perovskite nanocrystals is limited by complex synthesis space. Here, authors developed a self-driving lab that autonomously discovers and produces optimal scalable nanocrystals for next-generation photonic technologies.

The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the authors report that BRCA1/2 and ADAR1 are synthetic lethal, showing that ADAR1 depletion in BRCA1-mutant cells causes autocrine interferon poisoning

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.

Thermal contraction effect increases with time dominates the long-term deformation trend of the Heber geothermal field, while pressure effects of pressure fluctuation and poroelastic responses keep relatively stable and drive short-term changes.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

Targeted degradation has emerged as a powerful therapeutic modality. In this study, the authors develop a lipid-based platform to deliver recombinant bioPROTACs into cells for targeted protein degradation, providing a platform for efficient intracellular degradation of proteins that may elude chemical inhibition.

Here, the authors engineered probiotic bacteria to sense inflammatory biomarkers in the gut and respond by producing protein reporters that can be imaged noninvasively with ultrasound, providing a potentially easier and cheaper approach to diagnose and monitor IBD or other GI conditions.

The authors stabilize the SARS-CoV-2 nucleocapsid (N) dimer assembly using a short RNA and chemical crosslinker for EM analysis, revealing its domain arrangement and antigenic sites to advance understanding and guide pan-coronavirus therapeutic design.

Immune receptors regulate immune responses and are key cancer immunotherapy targets. Here, the authors designed helical concave scaffolds to bind convex sites in immune receptors, creating high-affinity protein binders for TGFβRII, CTLA-4, and PD-L1. Co-crystal structures confirmed their therapeutic potential.

Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

An atlas study of adipose tissue in people with obesity undergoing weight loss and their lean counterparts reveals that weight loss reduces cell senescence but cannot reverse all the metabolic problems caused by obesity.

Structural analyses of antibody-virus complexes offer critical insights into immune recognition mechanisms. In this report, we present how a patient-derived IgG recognizes a quaternary epitope on EEEV particles through strictly bivalent interactions.

Large-scale combination drug screens in cancer are extremely challenging because of the immense number of possible combinations. Here, the authors develop BATCHIE, a Bayesian active learning platform to design scalable and maximally informative drug combination screening assays; this is validated in retrospective and prospective cancer studies.

Protocadherin-1 (PCDH1) is a critical host factor for hantaviruses that can cause severe cardiopulmonary syndrome. Here, the authors map the binding site of the viral glycoprotein complex within PCDH1 and show that mutations engineered at this site can protect Syrian hamsters from viral challenge.

Oblique line scan microscopy achieves nanoscale spatial and sub-millisecond temporal resolution across a large field of view, enabling improved and robust single-molecule biophysical measurements and single-molecule tracking in both cells and solution.

A population of neutrophils in the skin produces extracellular matrix, providing a defence strategy by reinforcing the barrier properties of the skin and helping to block the entry of pathogens.

A high-throughput chemical screen identifies the salt-inducible kinase inhibitor HG-9-91-01 as a driver of β cell proliferation, acting through an ATF6-dependent unfolded protein response.

Here the authors use synthetic tools to control elements of the cytoskeleton during amoeboid migration. They uncover two feedback loops sufficient to generate cell polarity; one at the cell front in where branched actin polymerization increases Ras activation, and at the back, myosin filament assembly inhibits Ras activation.

Mehl and colleagues present a protocol for selecting aminoacyl-tRNA synthetase (RS)/tRNA pairs from a publicly available MaPylRS active site mutant library for specific and efficient incorporation of noncanonical amino acids into proteins.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Current media for neuronal cell and organoid cultures are suboptimal for functional imaging and optogenetics experiments, owing to phototoxicity and unphysiological performance. Here the authors formulate an optimised neuronal medium to support live cell imaging and electrophysiological activity.

By probing the essentiality of diverse genes encoding mRNA translation factors in different human cell types using CRISPR interference screens, Rodschinka et al. discover that human stem cells critically depend on proteins rescuing stalled or collided ribosomes.

Probiotic Escherichia coli Nissle 1917 is engineered as an antitumour vaccination platform optimized for enhanced production and cytosolic delivery of neoepitope-containing peptide arrays to safely induce specific, effective and durable systemic antitumour immunity.

Restoration of sight by subretinal photovoltaic prosthesis could be improved with next generation devices with smaller pixels. Here, the authors demonstrate safe removal and replacement of implants in rats, retinal integrity preservation and improved grating acuity with 22 μm pixel devices.

Currently there is neither a vaccine nor an effective treatment strategy available for COVID19. Here, Hurlburt et al. provide the crystal structure of a patient-derived monoclonal antibody neutralizing SARS-CoV-2 via shedding of the S1 subunit and competing for the receptor binding domain.

The induction of broadly neutralizing antibodies (bNAbs) is a goal of HIV-1 vaccine research. Here the authors demonstrate the ability of an HIV Env-derived immunogen to bind germline precursors of a class of bNAbs and to activate the corresponding B cells in a knock-in mouse model

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Carbon dioxide concentration has previously been used as a proxy for overall ventilation efficiency to indirectly estimate the risk of indoor SARS-CoV-2 transmission. Here, authors investigate whether the concentration of carbon dioxide also has a direct mechanistic role in improving transmission efficiency.

A metabolically bioactivated selective imidazothiazole nematicide shows comparable effectiveness at controlling plant root infection by Meloidogyne incognita to commercial nematicides, which are traditionally nonselective and toxic.

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.