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Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Long COVID (LC) involves a spectrum of chronic symptoms after resolution of acute severe acute respiratory syndrome coronavirus 2 infection. Barouch and colleagues show that LC is characterized by persistent activation of chronic inflammatory pathways and T cell exhaustion.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

Gel electrophoresis image analysis still largely relies on manual or semi-automatic tools, limiting both efficiency and reproducibility. Here, authors introduce GelGenie, an AI-driven open-source platform that rapidly detects gel bands under various conditions.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

A molecular glue induces CRBN homodimerization and degradation through degron mimicry, revealing a distinct glue mechanism and offering a tool to study CRBN biology.

Here, using samples from ~1,100 individuals, the authors define the nasal microbiome linked to Staphylococcus aureus colonization, identifying seven communities- either S. aureus-dominated or dominated by other bacteria.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

A non-precious metal cobalt phosphide hydrogen evolution catalyst is found to be active and durable in a commercial-scale polymer electrolyte membrane electrolyser.

Increasing evidence suggests that activation of oncogenic pathways contributes to an unfavorable tumor microenvironment. Here, the authors show that wild-type KRAS plays a key role in immune evasion in hepatocellular carcinoma by impairing interferon-mediated immunity and promoting resistance to immunotherapy via the EGFR/MEK/ERK pathway.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Acetic acid efficiently depolymerizes aliphatic and aromatic epoxy-amine thermosets used in carbon fibre-reinforced polymers (CFRPs) to yield recoverable monomers and pristine carbon fibres, which, based on process modelling, techno-economic analysis and life cycle assessment, could enable industrial recycling of CFRPs.

Our current understanding of neurofibromatosis type 1 (NF1) is based on patients ascertained through phenotype-first approaches, which estimate a low prevalence at 1 in 3,000. Here, the authors leverage a genotype-first approach in multiple large patient cohorts to demonstrate an unexpectedly high prevalence (1 in 1,286) of NF1 pathogenic variants with distinct disease associations.

Authors show that water trapped between 2D MXene sheets forms amorphous ice clusters at low temperatures, which cause a hysteresis of electrical conductivity. This structural rearrangement of water is affected by the presence of solvated cations, allowing reversible switching of the electronic properties of MXene films.

The Lamat programme supports undergraduate scholars from marginalized backgrounds to pursue scientific endeavours in astronomy and the planetary scientists by tailoring content to their specific strengths.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

When learning to make choices that simultaneously affect the self and others, asymmetric encoding of information guides future social behaviors across mutually beneficial, mutually costly, altruistic, and instrumentally harmful contexts.

Studies using human pluripotent stem cells and a mouse model of Down syndrome identify HMGN1 as a key contributor to congenital heart defects in individuals with Down syndrome.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A chromosome-level genome assembly for the Ninu (greater bilby) and genome sequences for the extinct Yallara (lesser bilby), together with resequenced genomes, shed light on the demographic history of Ninu and inform conservation plans for this culturally and ecologically important marsupial.

Current vaccines induce broadly cross-reactive cellular immunity against SARS-CoV-2 variants, including Omicron, and provide protection against severe disease despite a substantially reduced neutralizing antibody response.

During evolution, how adaptive walks cross fitness valleys remains unclear. This integrative study on monkeyflowers reveals that convergence in large steps (floral color and gene expression) drives a shift in pollinator attraction despite non-optimal fit, paving paths to reproductive isolation.

Hoang et al. developed a deep-learning framework called ENLIGHT–DeepPT that predicts therapy response based on imputed transcriptomics and shows predictive power across patient cohorts and cancer types.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

Microglial states throughout remyelination are incompletely understood. Here, the authors show that microglia form several states during the early stages of remyelination that coalesce into a partially resolved state that is dysregulated with age.

Since publication of the first issue of Nature Reviews Nephrology 20 years ago, advances across various subspecialities of nephrology have provided insights into disease processes and led to the development of new therapeutics for people with kidney disease. However, despite this progress, many kidney diseases remain untreatable, the costs of kidney disease care are immense, and vast inequities persist in disease burden and access to care. In this Viewpoint, we ask experts from several key subspecialties of nephrology to reflect on progress made over the past 20 years, remaining challenges and the steps needed to move the field forward.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Yeasts are exposed to oxidative stress during routine metabolism, bioproduction, and interactions with other organisms. Here, the authors use a machine learning classifier to identify genes that are predictive of resistance to oxidative stress across diverse yeast species.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Large-scale plasma proteomics of 10,527 samples from the Global Neurodegeneration Proteomics Consortium identified shared and disease-specific pathways in Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia.

Cui et al. find that open trade policy is a key factor for achieving low-cost solar photovoltaic supply chains. This conclusion holds even for regions, like Europe, that seek to localize solar production capacity.

Inhibition of haem synthesis is shown to lead to the accumulation of branched-chain amino acids in the brown adipose tissue of mice, which reduces UCP1 levels and impairs thermogenesis.

In November 2023, the Division of Aging Biology of the National Institute on Aging held a workshop to discuss the long-term effects of pregnancy on aging. A synthesis of these discussions and a set of considerations are presented in this Meeting Report.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

SARS-CoV-2 challenge of rhesus macaques demonstrates that the Ad26.COV2.S vaccine induces robust protection against both the WA1/2020 isolate and the B.1.351 variant of concern.

Here the authors report that chromatin-associated RNAs (caRNAs) could play both cis and trans-regulatory roles in establishing cell-type-specific chromatin architecture by showing their capability to improve the prediction of genome folding.

Solvent co-intercalation into graphite anodes for sodium-ion batteries is common; however, intercalation into cathodes is much less explored. Here, using operando experiments as well as theory, solvent co-intercalation in a range of layered sulfides is investigated.

Amado et al. develop a gene therapy for sporadic ALS using motor neuron-targeting AAVs to deliver RNAi targeting ataxin-2. In a mouse model, survival, strength, and disease-related pathology are improved; and human motor neurons are strongly transduced.