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Osteoarthritis is driven by epigenetic dysregulation, yet targeted therapies remain elusive. Here, the authors develop a cartilage-targeting hydrogel delivering BRD4-degrading PROTACs to suppress the BRD4- Nav1.7 axis and alleviate osteoarthritis.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

Extracellular vesicles from senescent endothelial cells transfer GPX4 to colorectal cancer cells, suppress ferroptosis, and promote resistance to neoadjuvant chemotherapy

Millisecond pulsar PSR J0435+3233, with a spin-down rate that is 100 times higher than those of other millisecond pulsars, occupies a unique position on the P–Ṗ diagram. This pulsar challenges classical recycling models and constrains spin-up theories.

Deep skin injuries often lead to scarring. Here, the authors show that restoring GAS6 via an mRNA-hydrogel platform enhances wound healing and reduces fibrosis in preclinical models.

Li and colleagues present CellScope, a tree-structured framework that reveals multi-level cellular hierarchies and gene functions in single-cell data. This approach provides clear clustering, intuitive visualization, and deep biological views into cell types and functions.

Atomically dispersed metal atoms on semiconductor surfaces alter the local surface carrier distribution. Here, the authors demonstrate the improvement of the SERS activity of titanate nanotubes by controllable loading with monoatomic W species.

This study provides a single-cell and spatial atlas of the prometastatic tumor microenvironment in esophageal squamous cell carcinoma and characterizes the immunosuppressive function of GPR116⁺ pericytes in cancer metastasis and immune evasion.

Compact laser-wakefield-driven X-ray sources show promise but suffer from poor conversion efficiency. New research demonstrates high-yield, hard X-rays generated by using carbon nanotube targets, instead of gases.

Remote boronate rearrangement of boronic acids to C = N bonds have substantial synthetic utility, however, this synthetic route has been limited by the need for preinstalled directing groups. Here, the authors introduce a lactam-driven dynamic directing strategy, enabling efficient 1,5- and 1,4-boronate rearrangements, advancing the functionalization of inactive C = N bonds and expanding synthetic methodologies.

Commonly used opioids for pain management primarily target the mu opioid receptor. However, mu opioid receptor agonists often come with harmful side effects. Here, the authors report the results of two phase 3 trials of HSK21542 (anrikefon), a highly selective activator of peripheral kappa opioid receptor agonists, for postoperative pain treatment following abdominal surgery.

The authors add GaSb to PbSe as an n-type dopant to form stable solid solutions with high power factor and high figure of merit. They find that the Ga and Sb atoms co-occupied the Pb sites, causing local structural distortion.

Nerve fibers relaying pain information from peripheral organs are normally supported by specialized glial cells called nonmyelinating Schwann cells. Here, the authors show that a secreted factor, SEMA3B, promotes nerve fiber-Schwann cell interactions necessary for suppressing pathological pain.

KN046 is a bispecific antibody targeting PD-L1 and CTLA4. Here the authors report the results of a phase II trial of KN046 combined with lenvatinib in patients with advanced hepatocellular carcinoma.

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.

Current methods to subtype brain tumors rely on invasive biopsies. Here, the authors develop a digital platform to regeneratively convert and catalytically enhance signals from rare circulating RNAs for blood-based characterization of brain tumors.

The development of carbon dioxide reduction catalysts at industrial current densities remains challenging. Here, the authors demonstrate that in situ electro-polymerization of cobalt phthalocyanine on a gas diffusion electrode achieves high carbon monoxide selectivity at high current densities.

Random lasers have traditionally been viewed as unpredictable light sources suited only for generating randomness. Here, the authors use deep learning to uncover hidden deterministic patterns within these emissions, enabling a method for secure cryptographic key distribution.

Preclinical studies have shown synergy in the combination of tifcemalimab (anti-BTLA antibody) with toripalimab (anti-PD-1 antibody) in lymphoma. Here, the authors report a clinical trial investigating tifcemalimab alone and in combination with toripalimab in patients with relapsed or refractory lymphoma.

Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.

Jia and colleagues profile human glioblastoma samples and identify a population of macrophages characterized by Siglec-9 that drives immune evasion and immunotherapy resistance via restriction of T-cell priming. Their therapeutic elimination synergizes with immunotherapy.

Sepsis, a systemic inflammatory response to bacterial infection, can lead to organ failure and death. Here, Chai et al.investigate the mechanisms behind the septic response and identify the role of oestrogen sulfotransferase in this process in mice.

The genetic risk of clear cell renal cell carcinoma is complex and the genes related are unclear. Here, the authors propose a deep reinforcement based model to identify risk genes.

The nitrogen reduction reaction is an extremely valuable but energy-intensive process. Now, a coordination polymer based on a [Zn–N₂–Zn] unit has been shown to promote the formation of ammonia under ambient conditions by a photocatalytic reaction. The N₂ moieties within the framework are reduced, creating unsaturated [Zn²⁺···Zn⁺] intermediates that are able to capture external N₂ and sustain the cycle.

Two amplified genes from chromosome 8q22—YWHAZ and LAPTM4B—are associated with metastatic breast cancer recurrence by promoting resistance to anthracyclines. YWHAZ codes for an antiapoptotic protein and LAPTM4B encodes a previously undescribed lysosomal protein.

Genetic code expansion enables precisely introducing chemical structures into proteins to improve their catalytic functions. In this study, the authors report the incorporation of genetically encoded Nδ-Vinyl Histidine (δVin-H) into an organocatalytic esterase and myoglobin, and improve the performance of the hydrolysis reaction and carbene transfer reactions catalyzed by the respective enzymes.

Dysregulated R-loops can compromise genome stability, leading to pathological consequences. Li et al. demonstrate that R-loop-induced poly(ADP-ribose) polymerase 1 activation orchestrates exonuclease 3′–5′ domain-containing 2-mediated R-loop resolution, thereby safeguarding genomic integrity.

Tuning compressive strain is an effective way to accelerate the oxygen evolution reaction kinetics. Here the authors show that anisotropic thermal expansion induces compressive strains on IrO6 octahedron in Sr2IrO4, shifting its d-band center downward and accelerating water oxidation kinetics beyond traditional thermal diffusion effects.

Live cell imaging of mitochondrial cristae is challenged by the unsuitability of current fluorescent probes and high phototoxicity. Here the authors develop a squarine variant probe (MitoESq-635) that is capable of longitudinal imaging of cristae with STED with minimal phototoxicity.

A field trial succeeded in eliminating populations of the mosquito Aedes albopictus through inundative mass release of incompatible Wolbachia-infected males, which were also irradiated to sterilize any accidentally-released females, and so prevent population replacement.

Using an integrated analysis on three independent large human datasets, Wang et al. map macroscale dysconnectivity in schizophrenia onto layer- and cell-type-specific microscale alterations. The authors identify different alterations of corticocortical and corticostriatal connectivity in schizophrenia and their relationship to different symptom dimensions and functional domains.

A good understanding of the mechanism behind organic electrooxidation is crucial for the development of efficient energy conversion technology. Here, the authors find that trivalent nickel is capable of oxidizing organics through a nucleophilic attack and electron transfer via a non-redox process.

Current genetic modification methods require regeneration using tissue culture. This study now reports a type of transformation technology, pollen magnetofection, that allows production of transgenic seeds in multiple species in a fast, culture-free manner.

Muons are conventionally produced from cosmic rays or with a proton accelerator. Now a proof-of-principle experiment demonstrates the feasibility of muon production with a laser-driven electron beam with gigaelectronvolt energy in a lead converter target.

The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.

The authors resolved large scale fresh and recirculated submarine groundwater discharge (SGD) and their associated nutrient fluxes in China’s coastal seas, revealing a dominant role of SGD in nutrient budgets.

The practical application of electrosynthesis of propylene oxide is hindered by limited performance. Here, the authors report a spatial decoupling strategy by utilizing the bromide mediator to link propylene and anode within separated reactors, realizing high-performance electrosynthesis of propylene oxide.

An optimal catalyst for nitrate electroreduction should satisfy the simultaneously optimized adsorption of intermediates. Here, the authors report a tandem electrocatalyst by combining Cu single atoms with Co₃O₄ nanosheets, enhancing the binding with NO₂⁻, thus promoting nitrate electroreduction to NH₃.

Interim analysis from the randomized phase 3 JUPITER-02 trial shows that the addition of anti-PD-1 toripalimab to standard gemcitabine/cisplatin as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma has manageable toxicity and improves progression-free survival, suggesting a potential new treatment standard in this setting.

Shape-changing materials have potential in a range of applications, but these transformations can be challenging to control. Here, the authors report the hydrophobic pseudo-hydrogel, which utilizes absorption-induced expansion via elastocapillarity to enable versatile soft robotic applications.

The integrated process of mechanochemical fractionation-assisted and solar-driven electrochemical reforming, followed by biological funnelling, enables the efficient upcycling of sewage sludge. This process not only co-produces valuable single-cell protein and green hydrogen but also effectively removes heavy metal contaminants.

Type 2 diabetes (T2D) is characterized by pancreatic beta-cell failure. Here, the authors show restoration of Phosphatidylinositol transfer protein alpha (PITPNA), a mediator of PtdIns-4-phosphate synthesis in the trans-Golgi network, in human T2D islets reverses impaired insulin granule maturation, exocytosis, and ER stress.

Gu et al. report that the OsSGS3-tasiRNA-OsARF3 module plays an important role in coordinating the trade-off between heat tolerance and disease resistance, which positively regulates thermotolerance but negatively modulates immunity in rice.

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.