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RUNX2⁺ keloid fibroblasts highly expressing ADRB1 produce bone matrix proteins in response to neurotransmitters from catecholaminergic nerves. Blocking this neuro-stromal interaction prevents fibro-osseous reprogramming and keloid progression.

Resistance to targeted therapies in cancer can be induced by metabolic rewiring. Here, the authors show that upregulation of the glucose transporter GLUT6 drives targeted-therapy resistance by diverting glucose metabolism to activate the anti-oxidative stress NRF2 pathway in lung cancer.

This study shows that Mg–Fe engineered biochar drives the formation of Mg–Fe layered double hydroxides, immobilizes carbonate, reduces sodicity, and stabilizes soil organic carbon via organo–mineral associations in soda saline–alkaline soils.

Polymer nanocomposites face a fundamental challenge in simultaneously enhancing strength and toughness, as current methods often compromise one for the other. Here the authors incorporate mechanically interlocked [2]rotaxane units into the interfacial layer of dynamically cross-linked polymer nanocomposites to enhance both strength and toughness.

Liang Guang et al revealed that cardiac CDK9 is activated in hypertrophic myocardium and directly binds to NF-κB P65, promoting its phosphorylation to drive inflammation and remodeling. This finding identifies CDK9 as a potential therapeutic target for hypertrophic cardiomyopathy.

Microbial biosynthesis of monoterpene esters remains a major challenge due to the limited repertoire of highly selective alcohol acyltransferases (AATs). Here the authors discovered and engineered AATs for various monoterpene esters using a dual-substrate microbial platform.

A new approach to magnetic resonance imaging, ‘multiplexed magnetic resonance imaging’, is reported, which enables high-resolution simultaneous multiparametric mapping of multiple molecules in standard clinical settings.

Difelikefalin is an FDA-approved KOR-targeted drug for chronic pruritus yet exhibits side effects. Here, researchers solve cryo-EM structure of difelikefalin KOR-Gi, identifying Y320^7.43 as a key bias residue. Substituting D-Phe1 with β-phenylalanine develops beta01 which retains analgesic/antipruritic efficacy via a unique receptor conformation that reduces adverse effects.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Developing high-performance organic ferromagnetic semiconductors is hindered by the coupling between radical generation and molecular assembly during synthesis. Here, the authors use topochemical reduction to enable radical generation in pre-ordered perylene diimide films, maintaining their long-range order and achieving room temperature ferromagnetism and semiconducting behaviour

UCl₃-type electrolytes show promise for all-solid-state batteries, yet their structure and Li⁺ transport remain debated. Here, authors reveal foreign cations reside in the amorphous phase, which serve as the dominant Li⁺ pathway yielding enhanced conductivity and low-temperature battery performance.

Deciphering cellular microenvironments at atlas scale remains challenging. Here, authors present a scalable contrastive learning framework using cell-centric subgraphs to map niches across platforms. They apply it to over 10 million cells to reveal spatial patterns in cancer and the brain.

This study reveals how collective spin excitations called magnons lose their spin in antiferromagnetic insulators, enabling long-distance spin transport and offering new design principles for future low-power spintronic technologies.

Plasmons in carbon nanotubes (CNTs) benefit from high quality factors but the modulation of their dispersion relation remains challenging. Here the authors report the observation of hybrid plasmon-phonon polaritons in CNT arrays coupled with 2D hexagonal boron nitride, showing frequency-dependent topological transitions and whispering-gallery modes.

The gut microbial-derived metabolite HMB induces hepatic SNHG9, which suppresses MYC translation via IMP2, thereby derepressing MAS expression. MAS promotes protective autophagy, and HMB supplementation mitigates acetaminophen-induced liver injury.

Personalized vaccines show some potential in leveraging tumor-specific adaptive immunity for cancer therapy. Here, this group reports an in-situ hydrogel vaccine serving as a sustained reservoir for a tumor-derived extracellular vesicle antigens for personalized cancer immunotherapy.

Emerging evidence suggests that organs age at different rates. This study identifies a mechanism by which the naturally hypoxic intervertebral disc ages relatively slowly, via selective autophagy of HIF-1α, and designs a small molecule to export this mechanism across tissues.

Spatial transcriptomics enables mapping of cell communication but is limited by low resolution and data sparsity. Here, authors develop a deep learning framework that integrates histology images with spatial RNA-seq for single-nucleus ligand-receptor analysis, uncovering tumor-immune interactions across multiple cancer types.

Standard of care CD19-targeting CAR-T therapy for Relapsed-Refractory Diffuse Large B Cell Lymphoma (r/r DLBCL) faces frequent resistance often driven by regulatory T cell (Treg) activation. This study identifies Timosaponin AIII (TAIII) as A2AR inhibitor for enhanced CAR-T activity while depleting CAR-Treg formation.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

Reti-Pioneer, a retinal imaging artificial intelligence framework, identified diverse systemic diseases and demonstrated feasibility in a primary care silent trial, offering a pathway toward scalable clinical evaluation.

Researchers repurpose Prussian Blue and Vitamin C to treat dangerously high potassium levels in mice. This approach safely traps potassium without releasing harmful sodium, offering an potential option for heart and kidney patients.

Rising electricity and freshwater needs limit conventional hydrogen production. Here, the authors report a self-sufficient, electricity-free system that harvests atmospheric moisture to produce green hydrogen, offering a scalable and sustainable path to alleviate global green-hydrogen scarcity.

A transferrin receptor-associating polyplex formed by complexing mRNA with modified polyethylenimine enables monocyte trafficking and lymph node targeting for potent and selective cancer vaccination.

Pyridine hydrogenation on supported metal particles is a powerful yet challenging synthetic transformation due to the strong coordinating effect of pyridine that limits hydrogen adsorption and activation. Here the authors adopt dealuminated Beta zeolite to entrap nickel nanoparticles and use the porosity of the support to effectively modulate pyridine and hydrogen activation.

Cation contamination has long hindered deployment of highly active platinum-alloy catalysts in commercial proton exchange membrane fuel cells. Now, a CO₂-assisted recovery protocol allows contaminants to be removed from inside an operating cell, potentially redefining the practical outlook for platinum-alloy catalysts.

Cancer cells exploit altered metabolic pathways to dynamically regulate epigenetic methylations. Here, the authors show the canonical metabolic and nonmetabolic functions of PRPS2 in enhancing ATP utilization and SAM biosynthesis, promoting RNA m⁶A methylation for lung tumorigenesis and metastasis.

Although lithium–sulfur batteries are prized for their sustainability, practical energy densities are often limited by heavy host materials. The authors report a graphdiyne architecture that integrates anchoring and catalytic functions, enabling ultrahigh sulfur loading and exceptional energy densities, even in pouch-cell configuration.

SLCO4C1 is known for regulating kidney diseases. This study showed SLCO4C1 regulates hepatic cAMP uptake to suppress lipogenesis in MASLD. Targeting this pathway by FGF21 or forskolin suppressed lipogenesis.

An anticancer drug secretion system based on engineered mammary organoids inhibits tumour recurrence in a mouse post-surgical breast cancer model and promotes mammary gland reconstruction.

Neural mechanisms underlying energy metabolism are not fully understood. Here authors show that Phf6-expressing neurons in the medial preoptic area as key regulators of physical activity and energy expenditure, revealing a neural mechanism underlying obesity in Börjeson-Forssman-Lehmann syndrome.

The condensation domain PvdL-C₃ is shown to synthesize the tetrahydropyrimidine ring of pyoverdine, revealing cyclization capability in a canonical non-ribosomal peptide synthetase domain. Structural and mutagenesis analyses identify key active site residues that control catalytic specificity and stereochemistry, providing a structural blueprint for enzyme engineering to produce bioactive peptides.

LRBA deficiency is associated with autoimmune disease and CTLA4 loss; this study identifies LRBA as a negative regulator of antitumor immunity and introduces LC427 as a promising small-molecule inhibitor of the CTLA4-LRBA interaction for cancer immunotherapy.

LHAASO has detected γ-ray emission with a spectrum extending to 2 PeV from the pulsar wind nebula (PWN) powered by PSR J1849-0001, indicating an extreme particle acceleration efficiency and challenging the current particle acceleration theories.

DNA in many bacteriophages contains unusual chemical modifications. Here, the authors discover that carboxymethylcytosine is a natural DNA base and reveal its role as an intermediate enabling further DNA hypermodification.

Xue et al. develop a foundation model for spectral analysis. It excels in multiple tasks, such as denoising spectra and quantifying trace molecules, and is especially promising in identifying metabolic biomarkers of diseases such as stroke, Alzheimer’s disease and prostate cancer.

Traditional iterative catalysis in RiPP biosynthesis typically modifies linear peptides. Here the authors discover GNAT enzymes that iteratively modify fully folded lasso peptides and engineer them to create lipolasso peptides with expanded chemical diversity.

TongGeometry both solves and proposes olympiad-level geometry problems. It uses guided tree search to find hard but concise problems, making advanced mathematical reasoning more accessible.

Thymine DNA glycosylase (TDG) was identified as a synthetic-lethal target in p53-deficient cancers through alterations in double-stranded RNA accumulation. A covalent small-molecule inhibitor of TDG exhibited potent efficacy against p53-deficient tumors.

The Rat1-Rai1 complex has important roles in Saccharomyces cerevisiae RNA polymerase II transcription termination, and Rtt103 copurifies with Rat1-Rai1. Here authors Chu and Tong report the structure of the Rat1-Rai1-Rtt103 complex.

Coral reefs are declining globally, but regional degradation drivers are poorly quantified. This study reveals that coral loss in the northern South China Sea is predominantly linked to human coastal activities, suggesting that tailored local management may effectively reduce reef collapse.

The authors reveal intrinsic long-range-order noncollinear electric dipole order in the van der Waals crystal WO₂Br₂, enabling pressure-driven 90° polarization rotation via multiple transition pathways and distinctive ultrafast phonon dynamics.

Reducing China’s CO₂ emissions is crucial to achieving global carbon neutrality. This Perspective synthesizes bottom-up and top-down estimates to develop a regional CO₂ budget for China and evaluate pathways and uncertainties towards net zero.