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Therapies combining chemotherapy and immune checkpoint inhibitors have shown limited efficacy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Here the authors report the results of a pilot phase 1 trial of neoadjuvant modified Folfirinox plus nivolumab in borderline-resectable PDAC, including safety, efficacy and immunological correlates.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

Chlorine electrosynthesis from seawater is limited by poor selectivity and stability under industrial-scale conditions. Here atomic-step-enriched ultrafine high-entropy alloy nanowires enable highly efficient chlorine evolution at 10 kA m⁻² for over 5,500 h through dynamic Pt–O active sites, reducing electricity consumption and feedstock costs for next-generation chlor-alkali processes.

Bees are crucial for the maintenance of healthy ecosystems, yet rigorous estimates of their species’ richness are lacking. This study estimates taxonomic gaps for bees around the world and provides a standardised method for occurrence data.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

LC retention time prediction of peptides and their modifications is useful but is hindered by variations in experimental parameters. Here, the authors show how fine-tuning a deep learning model on a wide variety of experimental setups and modified peptides substantially improves predictions.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

Transition metal-catalysed carbene reactions facilitate a number of transformations in organic chemistry. Here the authors report iron-catalysed cascade reactions—involving carbene and carbene radical intermediates—of alkyne-tethered diazo compounds for the construction of carbocyclic molecules.

Using cryo-EM, the authors identified 42 MIPs, including outer junction protein CFAP77 and outer dense fibers, in native doublet microtubules of Tetrahymena thermophila. Knockout of CFAP77 reduced ciliary beat frequency and led to outer junction damage.

Pancreatic ductal carcinoma is often diagnosed at a late stage due to challenges in detection. Here, the authors develop a serum metabolomics-based algorithm, which outperforms existing detection methods.

Osteoporotic fractures are a major global health burden. Here the authors show, using proteome wide Mendelian randomization, that nine circulating proteins influence forearm fracture risk and identify a novel protective role for ephrin A1

Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.

MsbA mediates the transport of lipopolysaccharide across the inner membrane. Here, the authors show specific MsbA-lipid interactions can tune the selectivity for binding ATP over ADP and present five structures of MsbA with one bound to lipid.

Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

Excess nitrogen fertilization in maize production harms the environment and society, yet farmers face yield risks when reducing inputs. Using field trials across the US Corn Belt, this study suggests that nitrogen rates can be reduced by 12–16% with minimal yield risk, reducing emissions and leaching.

This work reports optical studies of circular and linear dichroism to image, respectively, chiral and nematic spin ordering in the layered triangular-lattice antiferromagnet Co1/3TaS2. Phases with co-existing chirality and nematicity are revealed.

The role of the innate immune system in pancreatic cancer is largely unexplored. Here, the authors reveal a targetable cancer cell-intrinsic axis in pancreatic cancer comprising ASC inflammasome complexes that link innate immunity with mitochondrial function and metabolism.

Lactation is essential, but its genetic and epigenetic regulation is poorly understood. Here, Hanin et al. show that ZFP57 has an imprinting-independent role in controlling postnatal nutritional support, expanding its known prenatal epigenetic functions.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

Symbiotic bacteria can have exceedingly small genomes. This study finds that ancient bacterial symbionts of planthoppers have repeatedly evolved the smallest known genomes, losing most biosynthetic functions, revealing how extreme genome reduction shapes life at the edge of cellular complexity.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

Population-based studies from Sweden with replication in Norway identify associations between host genetic variants and gut microbial composition and implicate short-chain fatty acid chemosensors as modulators of gut microbial richness.

Here, using anatomy, transcriptomics, and functional assays, the authors reveal how Japanese wisteria climb using an unusual vascular architecture. Ectopic cambia arise from cortical cells and repurpose conserved cambium regulators, including KNOX genes.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

Aperiodic composite crystals were discovered that emulate 2D moiré materials, demonstrating a potentially scalable approach for producing moiré materials for next-generation electronics and a generalizable approach for realizing theoretical predictions of higher-dimensional quantum phenomena.

Reprograming the tumor microenvironment is a promising strategy to overcome resistance to immune checkpoint inhibitors (ICI) in patients with malignant melanoma. Here, the authors report a phase 1/2 study evaluating the combination of LOAd703 (viral-vector encoding CD40L and 4-1BBL) with atezolizumab (anti-PD-L1) in patients with ICI-resistant, malignant melanoma.

This study shows O₂-producing cyanobacteria likely prospered in silica- and iron-rich ancient oceans prior to the emergence of free O₂. Silica and day-night light cycles helped the microbes to overcome toxicity effects caused by oxygen radicals.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Most GWAS have focused on common variants or rare protein coding variants. Here, the authors interrogate the contribution of rare non-coding variants for anthropometric traits, identifying new genes associated with increased BMI and height.

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.

Thermal imaging lenses are typically made from expensive materials such as germanium and silicon. Here, the authors synthesise a sulfur-based polymer with high mid-wave infrared and long-wave infrared transparencies, presenting a high-performing, low-cost alternative to traditional thermal imaging lens materials.

Single-cell manipulation and processing techniques and improvements in mass spectrometry sensitivity make single-cell proteomic profiling feasible. This study presents a label-free approach for the characterisation of native N-glycans of single mammalian cells and ng-level blood isolates, demonstrating the potential to detect cell surface glycome changes at the single-cell level in health or disease.

Biocatalysis of the chemotherapy drug, doxorubicin, relies on the cytochrome P450 DoxA, which is inefficient. Here, the authors ameliorated the biosynthetic limitations by identifying DoxA redox partners and DnrV, which prevents product inhibition, helping improve microbial production.

Although antiretroviral therapies (ART) have expanded the life expectancy of patients with HIV, they are not curative due to the presence of latently infected cells. Here, the authors present IMC-M113V, a bispecific soluble TCR targeting the HIV peptide Gag_77-85 complexed to HLA-A*02:01 as an approach for targeting HIV reservoirs and test safety, tolerability and pharmacodynamics in a first-in-human clinical trial on 12 HLA-A*02:01-positive male individuals on ART.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

An Earth system model estimates that natural halogens, of marine biotic and abiotic origin, remove about 13% of present-day global tropospheric O₃. Projections suggest this ratio is stable through 2100, with high spatial heterogeneity, despite increasing natural halogens.

Rearrangement of the B cell receptor is sequential, and pairing of the successfully assembled heavy chain with the surrogate light chain proteins VpreB and λ5 to form the pre-B cell receptor is an important checkpoint signal for continued B cell development. Here, the authors show that λ5 plays a key role in the multi-step assembly process involving association-induced folding reactions.

Soft electrostatic actuators are crucial for advancing robotic systems that require adaptability and safety in unstructured environments. This study introduces ultralight soft electrostatic actuators utilizing solid-liquid-gas architectures, achieving significant improvements in power-to-weight ratio and actuation speed, exemplified by a 60% increase in jump height in a jumping robot compared to traditional designs.

Painful bone growth after injury or surgery often goes undetected until it is advanced and treatment options are limited. Here, authors demonstrate that a blood test detecting gene expression profiles in isolated circulating mesenchymal progenitor cells could detect early signs of this condition and track treatment success.

The electronic behaviour of complex oxides such as LaNiO₃ depends on many intrinsic and extrinsic factors, making it challenging to identify microscopic mechanisms. Here the authors demonstrate the influence of oxygen vacancies on the thickness-dependent metal-insulator transition of LaNiO₃ films.

Urbanization often leaves cities with fewer iconic species, and not just of animals. This study focusing on urban trees finds that urban trees have homogenized over large geographic differences but diversified over short ones.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.