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Hepatokine FGL1 mediates liver-kidney crosstalk in renal fibrosis. Upregulated by circulating inflammatory cytokines post-injury, it binds ALK5 to potentiate TGF-β signaling and promotes fibrotic progression, presenting a promising target for CKD.

Chemical imaging probes enable visualization of dynamic biological processes, but engineering high sensitivity probes remains challenging. Here, the authors present Sensight, a quantitative multivariate framework that integrates key photophysical and physicochemical descriptors to predict and optimize probe performance, and design G₃, a superoxide probe with high sensitivity for detecting early oxidative events.

Alternative splicing greatly expands the transcriptomic and proteomic diversity in vertebrates. Here, the authors develop a machine-learning tool to identify functional splicing events during hematopoietic cell differentiation, revealing new regulators of hematopoiesis.

The potential of detecting acidic tumor microenvironment (TME) is explored for early cancer diagnosis and treatment. Here, this group reports a pH-responsive ratiometric photoacoustic sensor that dynamically monitors TME acidity throughout HCC initiation, progression, and metastasis.

In this study, the authors show that citrulline accumulation exacerbates Fusarium wilt and that enhancing the soil’s citrulline-degrading function, particularly via the arcB gene, significantly reduces disease in continuous cucurbitaceous cropping systems.

Here the authors report a phase 3 clinical trial showing that Ecnoglutide, designed as a cAMP-biased GLP-1R agonist, improved glycaemic control versus placebo in adults with type 2 diabetes inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent.

Despite high efficiencies, all-perovskite tandem solar cells are hindered by thermal instability. Guo et al. address this issue by introducing a multi-Lewis-base modulator, which suppresses the formation of dense Cs-rich films in Pb-Sn perovskites to concurrently deliver high performance and stability.

Sclerostin impairs whole-body lipidandglucosemetabolism. Here, the authors further demonstrate that adipocytic sclerostin loop3-LRP4 interactionparticipatesin the impairment effect of sclerostin on whole-body lipid and glucose metabolism.

Spatiotemporal coordination of cellular and molecular events is crucial for cell fate commitment. Here, Yang et al. describe how transcription factors, signaling pathways, and epigenomic states regulate left-right patterning and axial mesendoderm lineage commitment during mouse gastrulation.

There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.

The structure of layered oxides dictates their properties as positive electrodes in sodium-ion batteries, but its rational design remains challenging. Here, authors employ electronegativity and configurational entropy as a design descriptor to guide the synthesis of a sodium-deficient layered oxide with an O3 stacking sequence, rendering good thermal and air stability.

Emerging evidence underscores biophysical characteristics of cancer cells as key modulators of cancer metastasis. Here, the authors reported a single-cell mechanophenotyping chip that screens deformable CTCs to reveal the hematogenous metastatic potential of bacteria-infected breast cancer.

The mechanical properties of inorganic solid electrolytes for Li batteries are typically characterised by a high Young’s modulus above 15 GPa and hardness above 1 GPa. Here, authors develop a cost-effective and mechanically compliant inorganic solid electrolyte, with reduced Young’s modulus and hardness of 1.41 and 0.22 GPa, respectively, for practical all-solid-state Li batteries.

The efficiency of selenium photovoltaics is hindered by the poor crystallization of the Se film. Wen, Li, Lu and colleagues use light to initiate Se crystallization, suppressing dewetting and enabling the formation of a continuous film, which achieves a certified efficiency of 10.3%.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

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.

Zhang, Huang, Wang, Long et al. report that NAT10 enhances serine uptake and biosynthesis in an ac4C-dependent mechanism, thereby promoting stemness and progression in acute myeloid leukaemia.

Yang et al. introduce a unified framework for liquid electrolyte design, integrating a forward predictive model with an inverse generative approach, where three generated high-conductivity candidates were identified and experimentally validated.

RNA-targeted degradation holds therapeutic potential but still needs more efficient tools. Here, authors develop dCasCMA, a platform that combines CRISPR targeting with a cellular degradation mechanism to efficiently degrade specific RNAs in live cells and in vivo, enabling multi-target therapies.

The role of protein UFMylation in cancer remains to be understood. Here the authors show that UFM1-specific ligase 1 and AKT positively regulate each other through UFMylation and phosphorylation in breast cancer cells, which could be therapeutically targeted by a cell-penetrating peptide through disrupting UFL1-AKT interaction.

Fast reendothelialisation of vascular grafts is important for maintain patency. Here, the authors report on a vascular graft that regenerates the neo-adventitia with lymphatic endothelial cells, which increases the recruitment of circulatory progenitor cells, achieving 90% patency in small-diameter arterial grafts.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Rosiglitazone, identified through integrative network-based drug repurposing and Mendelian randomization, alleviates age-related sarcopenia in mice. It enhances muscle strength and mass, possibly through gut microbiota remodeling, activation of Igf1 signaling, and inhibition of muscle atrophy–related ubiquitin ligases.

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.

In a cluster-randomized trial including 84 schools in China, schools that received the Life Gatekeeper Training Program for suicide prevention saw significantly reduced suicide stigma and improved willingness of teachers to intervene, compared to schools without the training.

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.

Protein condensates are engineered with tunable interfacial electric fields to drive electrochemical reactions, serving as a biomaterial platform for intrinsic electrogenic materials.

Organocatalytic allylic substitution of Morita-Baylis-Hillman (MBH) adducts constitute powerful transformations within organic synthesis. Here the authors present an asymmetric direct α-C–H allylic alkylation of NH₂-unprotected benzylamines with MBH adducts, using a bifunctional chiral pyridoxal catalyst, producing biologically important chiral γ-amino acid derivatives.

Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.

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.

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.

Huang et al. examine the impact of emotional distress on immune checkpoint inhibitor efficacy in advanced gastroesophageal cancer patients. Baseline emotional distress and elevated peripheral inflammatory markers significantly impair treatment outcomes through synergistic psycho-inflammatory mechanisms.

T follicular helper (Tfh) cells contribute to systemic autoimmunity. However, their involvement in the pathology of lupus nephritis (LN) remains unexplored. Here, by combining single-cell analysis of LN patient tissues and humanized mouse models, the authors show that mesangial cell-derived lactate regulates Tfh cell differentiation in LN by promoting Bcl6 lactylation and subsequent stabilization via K6 and k-29-linked polyubiquitination.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

A soft, biodegradable, wireless sensing device can monitor pressure, temperature and strain over long distances (up to 16 cm), maintaining accuracy across varying positions and angles.

Colonic smooth muscle cell (CSMC) hypertrophy and hyperplasia have been described in human ulcerative colitis (UC) and animal models. Here the authors show that mice lacking smooth muscle (SM) 22a develop spontaneous colitis which has RSAD2-driven mitochondrial dysfunction and inflammation in CSMC and show dependence on RSAD2 for colitis alleviation.

Precisely constructing homochiral helical nanostructures from achiral molecules by non-covalent interactions is challenging due to the untraceable handedness control at different hierarchical levels. Here, the authors present an aurophilicity-assisted orthogonal assembly strategy for the homochiral assembly of an achiral carbene-anchored trinuclear gold cluster with chiral amines.

Multi-omics profiling of the mucosal mycobiome in individuals with Crohn’s disease identifies C. sphaerospermum as a protective fungal species that counteracts intestinal inflammation and reinforces the intestinal barrier.