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The authors design a Pt/CuInP₂S₆/graphene heterostructure that achieves polarity-switchable photovoltaic current modulated by ferroelectric polarization. This enables programmable in-sensor computing, achieving high-performance visual tasks.

FcγRIIb captures its ligand and targets it to lysosomal degradation following endocytosis. Here authors design bispecific-antibody-like molecules they call FcγRIIb-targeting chimeras or FcRTACs, to capture antigens with one arm and degrade them via an FcγRIIb-binding second arm to promote the clearance of pathological protein aggregates.

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.

The DAWN study is a phase 3 clinical trial that demonstrates effective glycemic control of dorzagliatin as an add-on therapy to metfomin in patients with type 2 diabetes.

Variations in the valence states of nickel oxide hinder the growth of a uniform self-assembled monolayer (SAM). Here, authors develop a SAM with the oxidized product forming S−O−Ni bond at Ni³⁺-rich regions, achieving maximum device efficiency of 26.5% in operationally stable perovskite solar cells.

Osteoarthritis (OA) involves joint inflammation and degeneration, but its underlying causes are not fully understood. Here, the authors show that cholesterol triggers intercellular mitochondrial transfer to activate inflammatory chain reaction in joints and targeting this process can alleviate OA.

This study develops a unified electronic-geometric binary machine-learning descriptor to design efficient dual-atom catalysts for water purification. The optimized catalyst achieves rapid and persistent pollutant removal for 30 days.

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.

Nonalcoholic fatty liver disease (NAFLD) is often linked to disrupted bile acid homeostasis. Here, the authors show hyodeoxycholic acid (HDCA) ameliorates nonalcoholic fatty liver disease by inhibiting the formation of RAN/CRM1/PPARα nuclear export heterotrimer, resulting in increased nuclear localization of PPARα and activated fatty acid oxidation.

Obesity induces adipose stem cell (ASC) exhaustion and impairs adipose function. Here, the authors reveal that macrophages in visceral fat lose TIPE2 in obesity, which drive ASC ferroptosis via mitochondrial transfer, thereby disrupting adipose homeostasis and metabolic health.

The role of lysine crotonylation (Kcr) in MASLD pathogenesis remains unclear. Here, the authors identify a PCAF/SIRT7-IDH1 Kcr axis that ameliorates hepatic steatosis by boosting TCA cycle activity, uncovering a new mechanism and therapeutic target for MASLD.

Solvent engineering by the addition of 1,4-butane sultone in a perovskite precursor solution simultaneously enhances the crystallization of the perovskite and passivates defects, resulting in a power conversion efficiency of 26.5%.

Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible.

LYCHOS is a lysosome-localized cholesterol sensor involved in mTORC1 activity regulation. Here, the authors report the three-dimensional structure of LYCHOS bound to cholesterols, revealing the recognition mechanism for this molecule.

Optimized surface passivation deterministically enhances near-surface quantum dots’ resonance fluorescence from disappearance to improved emission.

Interlayer decoupling plays an essential role in realizing unprecedented properties. Here, authors construct a superlattice consisting of alternating layers of NbSe2 and highly porous hydroxide, realizing interlayer decoupling and thus realizing exotic monolayer behaviors in bulk materials.

Zhou et al. developed a specific small-molecule inhibitor of astrocytic Kir4.1 channels, Lys05, which exerts rapid-onset antidepressant effects in rodents without unwanted side effects, indicating Kir4.1 as a promising drug target.

Analysis of a large dataset of scanning transmission X-ray microscopy images of carbon-coated lithium iron phosphate nanoparticles shows that the heterogeneous reaction kinetics of battery materials can be learned from such videos pixel by pixel.

Liu and colleagues find differential effects of microglial apoE isoforms on brain function and microglial responses. ApoE3 enhances microglial responses, promoting brain function and reducing amyloid deposition and associated neurotoxicity, while the Alzheimer’s disease-associated apoE4 results in lipid droplet accumulation and impaired microglial responses, which are critical for limiting the development of amyloid pathology.

Genetically encoded iNap sensors allow imaging of NADPH with high spatiotemporal resolution in living systems. The iNaps cover physiologically relevant NADPH concentrations and are demonstrated in mammalian cells and live zebrafish.

Manipulating electrical and magnetic anisotropies will stimulate multi-terminal device applications. Here, the authors discover axis dependence of current rectifications, magnetic properties and magnon modes in van der Waals multiferroic CuCrP₂S₆.

Photoswitchable RNA-binding proteins enable the spatiotemporal control of RNA function.

The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.

Zuo et al. developed a highly bright and stable green fluorescent RNA for robust imaging of the dynamics of messenger RNA in living cells, enabling visualization of nonuniform and distinct distributions of different RNAs throughout stress granules.

Cas13d is a class 2 type VI-D CRISPR-Cas RNA-guided RNase. Here the authors present the high-resolution crystal structure of the uncultured Ruminococcus sp. Cas13d (UrCas13d)-crRNA complex and by combining structural, mutational and biochemical studies provide mechanistic insights into the CRISPR-Cas13d system.

Xia et al. provide a method for deep learning of 3D facial images to predict biological age with an accuracy of ±2.8 yr from chronological age and its correlation with lifestyle indicators and blood transcriptomic age.

Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in diverse cellular activities. Here the authors show a synthetic BRET-based transgene expression system that allows pulsatile and quantitative activation of gene expression both in live cells and in vivo.

The Clivias are a series of small, monomeric fluorescent RNAs that emit with a large Stokes shift in the orange–red. They enable multiplexed RNA imaging in live cells and BRET-based detection of protein–RNA interactions in mice.

E3 ubiquitin ligases regulate biological functions by ubiquitinating defined substrate proteins but overlapping specificities complicate the identification of E3-substrate relationships. Here, the authors construct an orthogonal UB transfer cascade and identify specific substrates of the E3 enzyme E6AP.