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.

This review article examines the intricate relationship between stem cells and the immune system, highlighting how stem cells protect themselves from infection and how immune cells regulate stem cell activity. It explores stem cell-specific defense mechanisms, such as antiviral RNA interference and the expression of interferon-stimulated genes, which differ from those in differentiated cells. The text further discusses the bidirectional communication between stem cells and immune cells at steady state and during injury, emphasizing the role of immune cells in orchestrating tissue repair. Finally, the article addresses the impact of inflammaging, or age-related chronic inflammation, on stem-immune crosstalk and its consequences for tissue repair and overall aging.

References:

• Poirier E Z. How stem cells respond to infection, inflammation and ageing[J]. Nature Reviews Immunology, 2025: 1-12.

This review article explores tumor-intrinsic factors that lead to resistance against immune checkpoint blockade in cancer treatment. It highlights how the genetic, transcriptional, and functional profiles of tumor cells significantly influence the effectiveness of immunotherapies like those targeting CTLA4 or PD1–PD-L1. The authors discuss several molecular mechanisms of resistance, including insufficient tumor antigenicity, impaired interferon signaling pathways, loss of MHC molecule expression, and the impact of various oncogenic signaling pathways (such as WNT–β-catenin, CDK4–CDK6, MAPK, and PTEN loss). Finally, the article identifies biomarkers of tumor-intrinsic resistance and examines existing and emerging therapeutic strategies aimed at overcoming these challenges and improving patient outcomes.

References:

• Kalbasi A, Ribas A. Tumour-intrinsic resistance to immune checkpoint blockade[J]. Nature Reviews Immunology, 2020, 20(1): 25-39.

This review explores the hallmarks of response, resistance, and toxicity to immune checkpoint blockade (ICB) in cancer treatment. It details various immune checkpoint molecules and strategies, including CTLA-4, PD-1, and emerging targets, alongside their clinical applications and associated adverse events. The text also thoroughly examines factors influencing ICB efficacy, categorizing them into host-intrinsic elements like tumor genetics, the tumor microenvironment (stromal and immune cells, metabolic status, microbes), and systemic host factors (gut microbiota, obesity, hormones). Finally, the review discusses host-extrinsic factors, or the exposome, which encompasses environmental, dietary, and behavioral influences, and highlights current and future diagnostic and therapeutic strategies to enhance treatment responses and mitigate toxicity.

References:

• Morad G, Helmink B A, Sharma P, et al. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade[J]. Cell, 2021, 184(21): 5309-5337.

This paper explores the evolving understanding of chemotherapy's role in cancer treatment, highlighting its capacity to do more than directly kill cancer cells. It details how conventional chemotherapies, initially chosen for their ability to inhibit cell proliferation, are now recognized for their immunostimulatory effects. The text explains these effects through "on-target" mechanisms that make cancer cells more visible to the immune system and "off-target" effects that influence immune cell populations and overall body physiology. Crucially, the source emphasizes the synergistic potential of combining immunogenic chemotherapies with immune checkpoint inhibitors (ICIs), a strategy increasingly explored in clinical trials to enhance long-term anti-cancer immunity. It also acknowledges the challenges and future directions in optimizing these combination therapies, including identifying ideal dosing, sequencing, and predictive biomarkers for improved patient outcomes.

References:

• Galluzzi L, Humeau J, Buqué A, et al. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors[J]. Nature reviews Clinical oncology, 2020, 17(12): 725-741.

This paper introduces the Cancer Immunology Data Engine (CIDE), a novel computational framework that integrates thousands of omics profiles to identify secreted proteins that modulate immunotherapy responses. The authors prioritized several candidate proteins, with a particular focus on acyloxyacyl hydrolase (AOAH). Through extensive in vitro and in vivo experiments across multiple tumor models, the study demonstrates that AOAH potentiates immunotherapies by enhancing T-cell receptor sensitivity and protecting dendritic cells, primarily by depleting immunosuppressive arachidonoyl phosphatidylcholines. The research highlights the potential of AOAH as a therapeutic target to improve the effectiveness of cancer immunotherapies, while also acknowledging the need for further studies on clinical application.

References:

• Gong L, Luo J, Yang E, et al. Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy[J]. Cell, 2025.