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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.

The authors present the full-length structure of the polymerase (L protein) from the severe fever with thrombocytopenia syndrome virus (SFTSV)—a segmented, negative-stranded RNA virus. The structure reveals important details with implications for the understanding of viral transcription and replication, and provides information on the organization of the polymerase core domain, entrance and exit tunnels, as well as the cap-binding and endonuclease domains.

Direct photocatalytic oxidation of methane into valuable oxygenated products remains highly challenging due to the inevitable overoxidation of the desired products. Here the authors report TiO₂ anchored with subnanometric MoO_x clusters for efficient oxidation of methane to C1 oxygenates with a high yield and selectivity.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Methods for constructing targeted synthetic communities using existing microbial resources remain limited. Here, the authors report a genome-scale metabolic model-integrated strategy for bottom-up construction of synthetic microbial communities in the plant rhizosphere.

In the dose-expansion cohort of this phase 1b trial, the EGFR×HER3 bispecific antibody–drug conjugate BL-B01D1 given to patients with metastatic esophageal squamous cell carcinoma led to encouraging clinical response rates, which need to be confirmed in larger efficacy trials.

Yang, Yan, Ma et al. provide a comprehensive lactylome analysis of hepatocellular carcinoma patients, and show that analysis of protein lactylation can help uncover mechanisms that couple metabolic flux with metabolic alterations in hepatocellular carcinoma.

The unique structure and mechanism of chanoclavine synthase (EasC), a haem catalase that uses superoxide for substrate transformation in ergot alkaloid biosynthesis, are revealed in this study, challenging established catalase mechanisms.

The sensitivity of Li-ion battery materials to moisture complicates their synthesis, storage, processing and recycling. Here, authors show that protonation causes structural instability in LiNi_xCo_yMn_1-x-yO₂ (0 <x,y < 1) and that controlled H⁺ and Li⁺ concentration in aqueous processing is critical.

Characterizing the superconducting gap structure in the high-temperature superconductor H₃S by means of tunnelling spectroscopy reveals that it, as well as D₃S, has a fully gapped structure, confirming the phonon-mediated mechanism of superconducting pairing.

The endoplasmic/sarcoplasmic reticulum (ER/SR) plays a crucial role in calcium signaling, but there are few methods capable of efficiently capturing ER/SR Ca²⁺ dynamics. Here authors develop a set of genetically encoded indicators enabling ratiometric super-resolution imaging and detection of elementary Ca²⁺ release in cardiomyocytes.

Cheng et al. identify a mitochondrial complex IV (CIV) deficiency in the brains of patients with sporadic amyotrophic lateral sclerosis (ALS). They demonstrate that defects in mitochondrial CIV induce ALS-like phenotypes in rats and highlight CIV deficiency as a potential risk factor and therapeutic target for ALS.

Two small-molecule modulators (Ebio2 and Ebio3) of the potassium channel KCNQ2 were developed using the same chemical scaffold. The modulators show opposite effects: Ebio2 acts as an activator, whereas Ebio3 serves as a selective inhibitor, with the different activity depending on the modulator tail group.

In the largest study so far of CAR T cells in patients with solid tumors, autologous CLDN18.2-targeting CAR T cell therapy was well tolerated in patients with advanced CLDN18.2-positive gastrointestinal cancers, with an overall response rate of 42.2% and a disease control rate of 91.1%.

Identification of a small molecule (Ebio1) reveals a unique activation mechanism for the KCNQ2 potassium channel. Ebio1 induces a twist-to-open movement in the S6 helices, creating an extended channel gate with enhanced conductance.

In a large prospective cohort of 1,090 pregnant women with a high risk of fetal genetic diseases, a cell-free DNA screening identified cases of aneuploidies, microdeletions and monogenic variants with high accuracy in concordance to standard diagnostic tests

Min Deng, Kai Wang and colleagues report genome-wide association analyses of amyotrophic lateral sclerosis in the Han Chinese population. They identify two new risk loci at 1q32 and 22p11.

Intestinal crypt-resident Acinetobacter radioresistens secretes indole acetic acid which activates an Ahr-Wnt-β-catenin-EphB2 signalling axis to promote intestinal stem cell homeostasis and prevent tumour initiation and colorectal cancer.

A recombinant vaccine that targets the receptor-binding domain of the spike protein of SARS-CoV-2 induces a potent antibody response in immunized mice, rabbits and non-human primates, and protects primates from infection with the virus.

Phosphoantigen-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor–mediated γδ T cell activation.

The progress of high-performance oxide-based transistors is essential for seamlessly integrating monolithic 3-D circuits into the CMOS backend. The authors propose using atomic layer deposition for ZnO due to its compatibility with low-temperature backend integration. They also successfully integrated ZnO TFTs with HfO2 RRAM in a 1 kbit 1T1R array, showcasing RRAM switching capabilities.

Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the treatment of haematological malignancies, but expanding applicability to solid tumours presents substantial challenges. This Review describes key strategies to optimize CAR T cell therapy for solid tumours across areas spanning from target selection to response and safety evaluation.

Sequencing of haploid sugarcane, Saccharum spontaneum, allows assembly of a prototypical version of the sugarcane chromosome set. This new reference genome will serve as a resource to accelerate sugarcane improvement.

Dongfeng Gu and colleagues report a genome-wide association study for coronary artery disease in Han Chinese individuals. They identify four loci newly associated with coronary artery disease.