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NIID is a neurodegenerative disease caused by GGC repeat expansions within NOTCH2NLC gene. Here, authors develop a precise gene-editing therapy that effectively treats the disease in multiple models.

Here they show that NONO collaborates with HOXA1 to modulate gene expression during early cardiomyocyte differentiation. This interaction facilitates activation of the Wnt signaling pathway, establishing the NONO-HOXA1-Wnt axis as a key mechanism in cardiac development.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Acute-on-chronic liver failure is a complex condition with varied definitions. Using unbiased clustering, the study identifies two distinct subtypes with markedly different 30-day mortality risks and highlights key determinants.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

Xu et al. identify the MondoA–TXNIP signalling axis as a regulator of antitumour immune surveillance in response to lactic acid in the tumour microenvironment.

Amplification and optimal noise filtering in hyperpolarized noble-gas spins of observations from distributed intercity quantum sensors monitoring for unexpected transient rotations of polarized spins set parameter range constraints in the search for axion dark matter.

An extreme barocaloric effect in NH₄SCN aqueous solutions is enabled by pressure-induced dissolution and precipitation, but without using a separate heat-transfer liquid.

The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.

The mechanisms underlying immunerelated adverse events (irAEs) following the combination of chemoradiotherapy with immunotherapy remain to be characterized. Here, single cell multi-omics and spatial transcriptomics on locally advanced cervical cancer patients identifies distinct effects on different immune cells associated with irAEs.

Tong and colleagues reveal a cross-species conserved mechanism where locus coeruleus-norepinephrine mediated arousal fluctuations drive an inverted U-shaped pattern of global functional connectivity, uncovering a network basis of the Yerkes-Dodson law.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

Finding efficient ways to release hydrogen from liquid carriers is key to advancing clean energy systems. This study introduces a resilient catalyst that drives highly selective hydrogen production from formic acid using low-grade heat.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

Hydrogen oxidation in alkaline media is limited by slow reaction kinetics. Here, the authors develop a family of bimetallic catalysts by theoretical analysis and reveal that RuIr achieves superior activity and durability through synergistic adsorption of hydrogen and hydroxyl intermediates.

The textile dyeing industry requires an easy-operation, atom economical, and efficient one-pot, one-step strategy for biosynthesizing indigoids. Here, the author report the engineering of artificial biosynthesis pathway to enable simultaneous production and in-situ bio-dyeing of indigoids for textiles.

Nasal colonization by Staphylococcus aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain.

Peritoneal metastasis remains a major clinical challenge due to the lack of effective therapeutic options. In this study, the authors present intraperitoneal programming of tailored chimeric antigen receptor macrophages (CAR-Ms) as a strategy against peritoneal metastasis.

Tao et al. study the role of TRMT6 in colorectal cancer, where it is upregulated and show that TRMT6 supports histone biosynthesis by stabilizing tRNA-Lys-TTT-1-1. Targeting TRMT6 reduced histone mRNA translation in a codon-biased manner.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Here the authors report an analysis of two large nationwide cohort studies, the UK biobank and NHANES, suggesting that accelerated biological aging mediate a proportion of the association between social determinants of health and all-cause and cause-specific mortality.

Lu and colleagues show that signaling through the lactate receptor HCAR1 in colorectal tumor cells promotes the recruitment of immunosuppressive CCR2⁺ PMN-MDSCs and that inhibition of HCAR1 by reserpine augments the CD8⁺ T cell-mediated antitumor immune response.

In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.

Acute myeloid leukaemia(AML) modifies the bone marrow(BM) microenvironment, impacting hematopoiesis. Here, the authors demonstrate that AML-modified BM endothelial progenitor cells(EPC) remodelling supports normal hematopoiesis after complete remission and this process is improved by the antioxidant N-acetyl-L-cysteine(NAC).

Authors provide real-world evidence demonstrating that rifaximin use in patients with cirrhosis and hepatic encephalopathy was associated with increased antimicrobial resistance, increasing the risk of infection-related complications and mortality.

Resistance to tyrosine kinase inhibitors (TKI) is a limitation to their use in treating chronic myelogenous leukemia (CML). Here, the authors show that targeting the ubiquitin peptidase USP47 overcomes TKI resistance and eliminates leukaemia stem/progenitor cells in primary and xenograft CML murine models.

A modular nanobody-based approach assembles combination vaccines by stably attaching diverse antigens to hepatitis E virus-like particles, preserving native immunogenicity and inducing broad protection against respiratory pathogens.

Ancient hyperthermals witnessed a reduction in the transfer efficiency of particulate organic carbon from the surface to the deep ocean due to warming-driven increases in microbial metabolism, which may have amplified this ancient warming.

Insulinomas develop from pancreatic β-cells and secrete insulin, but the underlying genetic defects are largely unknown. In this study, Cao et al. identify recurrent T372R mutations in the transcription factor YY1, and validate this hotspot mutation in 30% of insulinomas.

Previous structural studies of T cell recognition of SARS-CoV-2 have been confined to spike epitopes. Here the authors assess T cell recognition of SARS-CoV-2 nucleocapsid epitopes, which are more conserved than spike epitopes, providing structural insights into recognition of two epitopes.

Whole-exome sequencing analyses in a cohort of 2,140 participants with female infertility after recurrent in vitro fertilization, coupled with functional analyses, identified genes associated with oocyte and early embryo competence defects.

The adenomatous polyposis coli (APC)–Asef protein interaction is essential for colorectal cancer metastasis. Here, the authors present the rational design of a sensitivity-enhanced tracer for fluorescence polarization assays, enabling them to discover more efficient APC–Asef interaction inhibitors.

Bile acid metabolite isoallolithocholic acid attenuated inflammation in blood cells of patients with inflammatory bowel disease. Isoallolithocholic acid inhibited glycolysis and promoted oxidative phosphorylation to attenuate inflammation.

Metallic materials suffer severe strength degradation at elevated temperatures. The authors report exceptional high-temperature strength in an additive manufactured aluminum alloy with a thermally stable nanoscale eutectic cellular network.

Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma that affects the skin. Here authors show that CDK9 degradation of retinoic acid receptor α is a vulnerability for CTCL and develop a degrader targeting CDK9 that synergizes with all-trans retinoic acid to reduce CTCL tumor growth.

Strontium ruthenate is an odd-parity superconductor that could support Majorana fermions. Ying et al. report that the critical temperature doubles near lattice dislocations in this material compared with its bulk, arising from effects that could be found in other unconventional superconductors.

Syt1 is a primary Ca²⁺ sensor for secretion but the function of non-Ca²⁺ -affinitive Syt11 remains unknown. Here, authors identify strong but Ca²⁺ -inhibited lipid affinity of Syt11, and a Syt11-1-11 inter-switch during excitation-coupled exo-endocytosis.

The heat shock protein GP96 has been utilized as a potent adjuvant in vaccine formulations. Here, the authors present a viral vaccine platform based on the design of SARS-CoV-2 and HPV antigens fused to the N-terminus of GP96 and show that this vaccine design favor intact antigen delivery to the lymph nodes and induces potent long-term humoral and T cell responses after mice immunization

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Stress urinary incontinence (SUI) is a significant clinical challenge where less invasive treatment strategies that also address the pathophysiology of SUI are desirable. Here, Fang et al. engineer an injectable, thermo-responsive composite hydrogel incorporated with programmed stem cells that provides structural support to the atrophic urethral sphincter and promotes urethral sphincter regeneration, angiogenesis, and neurogenesis as a treatment strategy for SUI.

Macrophages undergo profound metabolic changes upon bacterial infection, including facilitated transport of the anti-bacterial metabolite Itaconate across the plasma membrane and membranes of vacuoles that contain the invading bacteria. Here authors identify MCT1/4 as transporters of itaconate, responsible for the regulation of intracellular and bacteria-containing vacuoles and thus macrophage antibacterial function in a Salmonella model of infection.

Previous clinical studies suggested that Insulin-like growth factor binding-protein 7 (IGFBP7) is elevated in early stages of diabetes. Here authors showed tubule and glomerular-specific IGFBP7 promotes diabetic kidney disease.

Modulation of regulatory T cells (Treg) in the tumour environment is a potential avenue to bolster anti-tumor immunity. Here Liu et al show that perturbation of the negative feedback loop involving STAT1- IFITM3 influences anti-tumor immunity, and that IFITM3 or STAT1 deficiency resulting in the fragility of tumor-infiltrating Treg cells.