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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.

Lu et al. characterize cis-regulatory element dynamics at different stages of colorectal cancer progression and identify a functional variant associated with increased colorectal cancer risk because of selective transcription factor binding.

Mixed matrix membranes capable of breaking the permeability-selectivity trade-off suffer from the inefficient and disconnected bulky transport channels as well as low compatibility between nanomaterials and polymers. Here the authors propose an original photothermally triggered in-situ gelation approach to elaborate a nanofiber-interwoven gel membranes with tunable 3D-interconnected ultrafast transport channels for highly-selective CO₂ separation.

The apelin receptor regulates heart and metabolic health via G-protein and β-arrestin signaling pathways. Here, authors present receptor-β-arrestin complex structures with distinct stoichiometries that provide insight into biased signaling, guiding targeted drug design.

Viral diversity and abundance in bats are incompletely understood. Here, analyzing individual bat viromes, the authors observe a high frequency of co-infection and spillover among the animals and identify viruses with the potential to infect humans or livestock.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Many thrombolytic agents depend on plasminogen, leading to D-dimer accumulation. Here, Tang et al. report a plasminogen-independent thrombolytic enzyme that degrades blood clots and D-dimer without plasminogen.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a drug target for inflammatory bowel disease (IBD), impacting immune cell movement, but current treatments carry immunosuppression risks. Here, the authors show that a Gi-biased S1PR1 agonist, SAR247799, protects the endothelial barrier in IBD models without affecting immune cell egress, offering a potential new treatment strategy.

The photocatalytic reforming of plastics into value-added chemicals offers a promising strategy to address environmental challenges while providing significant energy benefits. Here, the authors develop modified carbon nitride with enhanced visible light absorption, effectively anchoring under-coordinated IrN₂O₂ sites to catalyze the oxidation of persistent plastic derivatives.

Researchers unveiled the structural details of sphingomyelin synthase (SMSr), shedding light on its role in sphingolipid biosynthesis. SMSr transfers the phosphoethanolamine from PE to ceramide, adding complexity to the field of lipid homeostasis.

The economical electrosynthesis of H₂O₂ is limited by expensive ion exchange membranes. Here, the authors report a bubble shielding strategy to suppress H₂O₂ degradation by reverse engineering the gas-water-electrode interface, thus enabling high concentrations of H₂O₂ in membrane-free electrolyzer.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Trained on a medical knowledge graph, a foundation model is used to rank drugs as potential indications and contraindications across 17,080 diseases, identifying therapeutic candidates in a zero-shot framework even for diseases with limited treatment options or no existing drugs and outperforming existing models by a large margin.

A smartphone-based system, designed to induce a steady gaze in children using cartoon-like video stimuli, can identify visually impaired children across a wide range of ophthalmic disorders, based on analysis of gazing behaviors and facial features.

The authors show that adriamycin induces global changes on chromatin conformation associated with phase transitions mediated through Histone H1.

Developed on cytology images of hydrothorax and ascites from 57,220 cases at four hospitals, a deep-learning model shows high accuracy in tumor origin prediction and presents prognostic value when patient treatment is consistent with the cancer origin predicted by the model.

Ovarian cancer is common among women and is the leading cause of death from gynaecological malignancies. Here the authors identify two previously unknown genetic variants that increase the risk of epithelial ovarian cancer in Han Chinese women.

Here the authors used an evidence-based strategy to prioritize causal pleiotropic variants of autoimmune diseases, and revealed  that rs4728142 modulates aberrant IRF5 alternative promoter usage by ZBTB3-mediated chromatin looping.

During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.

Cells maintain a narrow physiological pH by exchanging intracellular bicarbonate for extracellular chloride. Here, authors determine the cryo-EM structures of human anion exchanger 2 (AE2) in five major operating states and one transitional state, to collectively demonstrate the process of pH-balancing.

Qing Lan and colleagues report the results of a genome-wide association study of lung cancer in never-smoking women from Asia. They identify three new susceptibility loci and confirm three other previously reported associations.

We report on the structures of the TAAR1–G-protein complex when bound to methamphetamine and other amines.

Macrocyclization of bioactive acyclic molecules provides a potential avenue to yield novel chemical scaffolds with improved pharmacological properties. Here, the authors propose a deep learning based macrocyclization method to generate diverse macrocycles from a given acyclic molecule.

Identification of shared genetic determinants of cardiovascular and cerebrovascular diseases, along with cardiometabolic risk factors, reveals the role of blood pressure and lipid traits, which may facilitate the development of new drug targets.

Hongbing Shen and colleagues identify three new susceptibility loci for lung cancer in the Chinese population. Their follow-up analyses suggest that two of these loci interact multiplicatively with smoking dose to influence lung cancer risk.