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Although river protection is core to social and environmental well-being, the extent to which river conservation policies are effective is difficult to assess. This study reveals that, under all relevant protection mechanisms in the contiguous USA, only 12% of rivers are adequately protected.

This Commission aims to resolve the current dialysis policy challenges in Thailand and generate lessons for the global kidney community by drawing on empirical evidence, systems thinking and multidisciplinary expertise to generate policy goals and recommendations.

In maize, ZmDapF1 suppresses the activity of ZmMDH6 in chloroplasts, exacerbating oxidative damage under drought. Knocking out ZmDapF1 or using its favourable allele with lower gene expression enhances drought resilience without yield penalty.

The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer’s disease. Here, Brutman et al. identify a deletion common in people of African ancestry that reduces the relative risk conferred by the APOE-ε4/ε4 genotype.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

Haldane’s rule suggests that in hybrid crosses, the heterogametic sex is often rare or sterile. This study crosses Caenorhabditis nematodes, and determines that an underlying feature of Haldane’s rule is incompatibility between a sex chromosome derived from only one species and autosome pairs from both.

Japonica subspecies has a lower nitrogen use efficiency (NUE) than that of indica rice. Here, the authors show that natural variations in the NIN-like protein 4 (OsNLP4) encoding gene are responsible for the divergence and introgression of the indica OsNLP4 allele into elite japonica cultivar can increase NUE and grain yield.

Crop choice strongly influences irrigation energy needs. Chiarelli et al. provides crop specific irrigation energy data, showing that irrigation under the current scenario uses 1.38×10⁹ GJy^-1 and under sustainable expansion, will use 1.62×10⁹ GJy^-1.

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.

Seed traits are critical for soybean yield and quality. Here, the authors report a NF-YA transcription factor gene SW14 regulates soybean seed traits without affecting other agronomic traits by inhibiting GmLEC1-mediated transcriptional activation.

O’Shea and colleagues establish that optimisation of charge and stability is sufficient to enable any single-chain variable fragment intrabody to function within the cell. The authors use AI-led inverse folding to optimise intrabody characteristics, and they present hundreds of intrabody sequences targeting sixty cytoplasmic proteins.

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

Mangrove ecosystems are facing severe climate threats. However, this study shows that strategically expanding protected areas to include the most climate-resilient sites can safeguard biodiversity and ecosystem services for the future, and this can be achieved with only a modest increase in protected area.

CD38 is highly expressed by antibody-secreting cells (ASC) and depleting antibodies targeting CD38 have the potential to treat autoimmune diseases with ASC involvement. Here authors treat systemic lupus erythematosus patients with the ASC-depleting anti-CD38 monoclonal antibody daratumumab in addition to dexamethasone in the frame of a single arm, open-label phase 2 clinical trial to show marked improvements in their clinical and immunological status.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

GDF15 has been associated with cancer-associated cachexia. Here, the authors show that STK11/LKB1 loss-of-function mutations in non-small cell lung cancer result in an exaggerated integrated stress response culminating in the tumor cell secretion of the cytokine GDF15 promoting cachexia.

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.

Johnson et al. link ARIA, a complication of anti-amyloid therapy, to clonal expansion of cytotoxic CD8 + T cells with glycolytic reprogramming and vascular trafficking potential, with implications for biomarker development and risk mitigation.

Structural variants are an underexplored source of genetic diversity. Here, the authors use phased pangenome graphs to improve detection of these variants in dairy cattle and link these variants to traits of economic importance.

Most kiwifruit species are vulnerable to high levels of heat stress. Here, the authors report natural variation at the GATA transcription factor binding site of EGY3 gene mediates chloroplastic ROS homeostasis to confer kiwifruit thermotolerance.

A streamlined blood test using mass spectrometry improves measurement of amyloid-β for early Alzheimer’s disease diagnosis, requiring less sample volume and reagents while maintaining high accuracy, sensitivity and strong agreement with brain imaging.

This study quantifies Brazil’s soil carbon debt (1.40 Pg C) and demonstrates that improved agricultural practices enhance carbon recovery. The findings reveal Brazil’s significant capacity to mitigate emissions and influence global carbon markets.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Contact matrices are used to describe social mixing patterns and inform mathematical models of disease transmission. Here, the authors evaluate the accuracy of synthetic contact matrices generated using mobility data compared to those derived empirically through surveys.

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

The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Wafer bonding has allowed the synthesis of twisted interfaces which support polar discontinuities in ferroelectric lithium niobate. Two-dimensional sheet conductivity arises but is suppressed when twist angles lead to interfacial lattice aperiodicity.

Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

Chromatin states need to be maintained during DNA damage repair. Here, the authors expand the histone chaperone network involved in repair-coupled chromatin restoration and highlight a mechanistic coordination between old and new histone dynamics.

Plastids, photosynthetic organelles in plants and algae, originated from cyanobacterial endosymbiosis. Here, Shrestha et al. use metagenomics to expand plastid diversity and provide evidence for two independent origins of secondary red-algal plastids.

Dimorphic organisms switch between two distinct life forms, but how a single genome controls the genetic program for both states is unclear. The study identifies hundreds of convergently evolved gene families and two regulator genes, dkl and dfl, that coordinate expression to optimize the two morphologies of Mucorales fungi.

Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.

Here, the authors combine bioinformatic, mass spectrometric, and sequencing-based mapping tools to identify previously undescribed phosphorothioate epigenetic systems widespread in the human gut microbiome.

This study applies machine learning to fMRI data to map developmental variations in functional connectivity, uncovering heterogeneity across individuals and cortical regions that predicts neurocognitive maturation in youth.

Aerial surveys over the Permian Basin found 500+ major methane leaks, many recurring. A few sites leaked continuously and offer quick mitigation wins. These super-emitters may produce ~50% of regional emissions, underscoring the need for frequent monitoring.