This review article from Nature Medicine explores the future of organ transplantation, highlighting innovative strategies to overcome donor shortages and improve patient outcomes. It details how artificial intelligence (AI) is being used to optimize organ allocation, refine rejection monitoring, and personalize immunosuppressive regimens, while xenotransplantation has progressed through multi-gene editing of donor pigs to mitigate hyperacute rejection. The text also covers regenerative medicine approaches, such as stem cell therapies, 3D organoids, and bioprinting, which aim to create patient-specific tissues and reduce the need for lifelong immunosuppression. Ultimately, the article emphasizes that the integration of these technologies, coupled with ethical and regulatory frameworks, is crucial for advancing transplant medicine globally.

References:

• Loupy A, Preka E, Chen X, et al. Reshaping transplantation with AI, emerging technologies and xenotransplantation[J]. Nature Medicine, 2025: 1-13.

This paper details the creation of a comprehensive, molecularly-defined, and spatially-resolved cell atlas of the entire adult mouse brain using Multiplexed Error-Robust Fluorescence In Situ Hybridization (MERFISH) technology. Researchers imaged over 1,100 genes in approximately 10 million cells, integrating this data with single-cell RNA sequencing to identify more than 5,000 transcriptionally distinct cell clusters and over 300 major cell types. The atlas was registered to the Allen Mouse Brain Common Coordinate Framework, allowing for the systematic quantification of cell-type composition and organization across various brain regions. This work also identified spatial modules, spatial gradients, and inferred cell-type-specific interactions, including potential molecular (ligand-receptor) bases for these interactions, thereby offering profound insights into the brain's cellular architecture and a foundation for future functional investigations.

References:

• Zhang M, Pan X, Jung W, et al. Molecularly defined and spatially resolved cell atlas of the whole mouse brain[J]. Nature, 2023, 624(7991): 343-354.

This article details the creation of a comprehensive, high-resolution cell-type atlas for the entire adult mouse brain. The research involved systematically generating two types of large-scale, single-cell-resolution transcriptomic datasets using scRNA-seq and MERFISH technologies. The study organizes over 5,300 distinct cell types into a four-level hierarchical taxonomy (classes, subclasses, supertypes, and clusters), further categorized into seven "neighborhoods" based on molecular and anatomical relatedness. A significant finding highlights the strong correspondence between a cell type's transcriptomic identity and its precise spatial location, with transcription factors playing a major role in defining cell-type identities. The atlas identifies diverse neuronal populations by neurotransmitter type (glutamatergic, GABAergic, cholinergic, dopaminergic, serotonergic, noradrenergic, and histaminergic), including instances of co-release, and also classifies non-neuronal cells like astrocytes and oligodendrocytes, revealing their regional specificities and interactions within the brain.

References:

• Yao Z, Van Velthoven C T J, Kunst M, et al. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain[J]. Nature, 2023, 624(7991): 317-332.

This article introduces a Stereotaxic Topographic Atlas of the Mouse Brain (STAM), a groundbreaking three-dimensional (3D) reference atlas with an isotropic 1-micrometer resolution. Developed using continuous micro-optical sectioning tomography and Nissl-based cytoarchitecture, it provides highly detailed 3D topographies of 916 brain structures, enabling single-cell level spatial localization. The atlas includes an informatics platform for visualization, sharing, neuronal circuit mapping, and intelligent stereotaxic surgery planning. This novel tool addresses limitations of traditional atlases by offering arbitrary-angle slice generation and interoperability with existing atlases, significantly advancing large-scale brain mapping research.

References:

• Feng Z, Li X, Luo Y, et al. A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolution[J]. Nature, 2025: 1-9.

This paper explores how certain bacterial proteins called functional amyloids, specifically curli fibers, provide a robust defense mechanism against predatory bacteria like Bdellovibrio bacteriovorus and even phages. The research identifies that curli fibers act as a physical barrier or "suit of armor", preventing predators from accessing and infecting bacterial cells. The study demonstrates that this curli-mediated defense is widespread among E. coli strains and that other evolutionarily distinct functional amyloid systems, such as those found in Pseudomonas, offer similar protection. This work highlights the diverse and complex strategies bacteria employ to protect themselves from microbial threats, suggesting functional amyloids play a significant role in bacterial immune responses.

References:

• Ledvina H E, Sayegh R, Carale R O, et al. Functional amyloid proteins confer defence against predatory bacteria[J]. Nature, 2025: 1-8.

This article explores how metabolism influences the structural evolution of enzymes over 400 million years in Saccharomycotina yeasts. Using advanced tools like AlphaFold2, researchers analyzed thousands of enzyme structures to reveal hierarchical patterns of evolution shaped by metabolic properties across various scales, from species-wide specialization to molecular interactions. Key findings indicate that enzyme evolution is constrained by catalytic function, reaction mechanisms, interactions with small molecules, and metabolic costs, with binding sites being the most conserved and surface residues evolving most rapidly. The study highlights how factors like protein abundance, metabolic flux variability, and enzyme class dictate amino acid substitutions and cost optimization, ultimately establishing a model where enzyme structure is intimately linked to its catalytic role and metabolic environment.

References:

• Lemke O, Heineike B M, Viknander S, et al. The role of metabolism in shaping enzyme structures over 400 million years[J]. Nature, 2025: 1-10.

This article explores the impact of whole-genome doubling (WGD) on the evolution and immune responses in high-grade serous ovarian cancer (HGSOC). The researchers utilized single-cell whole-genome and RNA sequencing, alongside high-resolution immunofluorescence microscopy, to analyze patient tumor samples and cell lines. A key finding is that WGD is an ongoing mutational process that increases cellular diversity and chromosomal instability. The study reveals that while inflammatory signaling is activated in tumors with low WGD, WGD-high tumors develop mechanisms to suppress immune responses, including altered cell-cycle regulation and STING1 repression. These insights into WGD's role in tumor progression and immune evasion offer potential avenues for improved therapeutic strategies in HGSOC.

References:

• McPherson A, Vázquez-García I, Myers M A, et al. Ongoing genome doubling shapes evolvability and immunity in ovarian cancer[J]. Nature, 2025: 1-10.

This article explores the planetary boundaries framework, which defines a "safe operating space for humanity" across nine critical Earth system processes. The authors use an Integrated Model to Assess the Global Environment (IMAGE) to project the state of eight planetary boundaries under various scenarios, including current trends and targeted environmental policies, through 2050 and beyond. The research indicates that business-as-usual approaches will lead to further environmental degradation, with most boundaries remaining transgressed even with ambitious interventions. The study emphasizes the urgent need for comprehensive and ambitious policy measures that extend beyond climate change to address the multi-dimensional nature of environmental challenges, acknowledging the role of societal and institutional feasibility in implementing these transformations.

References:

• van Vuuren D P, Doelman J C, Schmidt Tagomori I, et al. Exploring pathways for world development within planetary boundaries[J]. Nature, 2025: 1-7.

This article challenges the traditional understanding of tumor necrosis as a passive process, instead demonstrating that neutrophils actively induce tumor necrosis and promote metastasis. The research identifies a specific population of "vascular-restricted" neutrophils (Ly6GHighLy6CLow) that form neutrophil extracellular traps (NETs), leading to vascular occlusion and localized hypoxia within tumors. Crucially, the study shows that cancer cells in these oxygen-deprived (perinecrotic) regions undergo epithelial-to-mesenchymal transition (EMT), a process linked to increased metastatic potential. Furthermore, genetically or pharmacologically blocking NET formation significantly reduced both tumor necrosis and metastatic spread, highlighting a novel, targetable pathway for cancer therapy.

References:

• Adrover J M, Han X, Sun L, et al. Neutrophils drive vascular occlusion, tumour necrosis and metastasis[J]. Nature, 2025: 1-12.

This research explores the impact of non-antibiotic prescription drugs on the gut microbiome and susceptibility to infections. By analyzing data from over one million individuals, the study identifies specific medications, such as the cardiac drug digoxin, that increase the risk of gastrointestinal infections. The researchers then validate these findings in mouse models, demonstrating how digoxin alters gut microbiome composition and weakens immune defenses against pathogens like Salmonella. Ultimately, the findings highlight a novel mechanism involving a specific β-defensin that, when induced by digoxin, reduces beneficial bacteria and increases vulnerability to infection.

References:

• Kumar A, Sun R, Habib B, et al. Identification of medication–microbiome interactions that affect gut infection[J]. Nature, 2025: 1-10.