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Intracellular pathogens such as Mycobacterium tuberculosis can promote their survival within infected cells by preventing lysosomal acidification. Here, the authors show that M. tuberculosis secretes a protein that promotes phosphorylation of a subunit of the host vacuolar ATPase, thus inhibiting V-ATPase assembly and lysosomal acidification.

Soil-based compound dry-hot extremes represent a critical yet underappreciated driver of ecosystem stress. This study shows that their frequency and coverage area have increased markedly in China due to anthropogenic soil warming, which may pose growing adverse impacts on vegetation productivity.

Cell-cell adhesion plays critical roles in maintaining and regulating cellular functions. Here, authors present a diffusive N-cadherin functionalized hydrogel that provides cell-cell adhesion cues to modulate intercellular communication to promote neural regeneration for treatment of traumatic brain injury.

Developing hafnium dioxide-based high-κ dielectrics via morphotropic phase boundaries remains challenging. This study proposes a thermal-stable high-κ strategy via coherent interface design and elucidates the atomic-scale enhancement mechanism.

Electrochemical CO reduction to multi-carbon products offers a carbon-negative approach to produce chemicals, but the intricate reaction pathways lead to a broad spectrum of products. Now it has been shown that alkali cations alter the mechanistic pathways that govern the reaction selectivity involved in the formation of hydrocarbons versus oxygenates.

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.

Topological interface states typically support the propagation of a single state in each direction, which limits their applicability. Now, co-propagating states are achieved in a photonic topological insulator system.

Cutaneous tuberculosis is an infectious disease associated with extracellular matrix remodeling and granuloma-driven fibrosis. Here, the authors present an in vitro model of this disease using skin organoids infected with Mycobacterium tuberculosis, and describe infection-induced alterations in specific pathways and cell populations.

The reconstructed Holocene Australian summer monsoon in this study, together with the Asian monsoon records, show that the coupling evolution of Holocene Asian-Australian monsoon was dominated by the thermal imbalance between two hemispheres.

LRBA deficiency is associated with autoimmune disease and CTLA4 loss; this study identifies LRBA as a negative regulator of antitumor immunity and introduces LC427 as a promising small-molecule inhibitor of the CTLA4-LRBA interaction for cancer immunotherapy.

Hirschsprung disease, characterized by the absence of ganglion cells leading to functional bowel obstruction, can be treated with surgery. Here, the authors report that preoperative nutritional support in children with Hirschsprung disease reduced the risk of postoperative enterocolitis by comparison to standard of care in a randomized controlled trial.

The precise molecular and physiological functions of the iron transporter Slc22a17 remain poorly understood. Here authors report mice lacking Slc22a17 expression in the brain suffer from iron overload, oxidative stress, and learning deficits.

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.

Early human embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here the authors present LiCAT-seq, a method enabling simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells and map chromatin accessibility and transcriptome landscapes for human pre-implantation embryos.

Adenine base editors (ABEs) are powerful tools for gene therapy, though efficient versions of ABEs often induce excessive undesired editing events, limiting clinical application. Here, authors developed a Language Model to design a more precise ABE that can correct pathogenic point mutations and enable gene therapy in vivo.

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.

Heterogeneity in gene expression and epigenetic states exists across individual cells. Here, the authors develop scCAT-seq, a technique for simultaneously performing ATAC-seq and RNA-seq within the same single cell.

Osteoporosis was revealed to pyroptosis-related inflammation. Here, the authors show multifunctional microsphere can retard osteoporosis by restoring bone homeostasis thorough pyroptosis blockade and hydrogen-mediated modulation of inflammation.

By resonant excitation of an InAs quantum dot embedded in a microcavity, a deterministic single-photon source is demonstrated. Single-photon purity of 0.9795(6), photon indistinguishability of 0.9856(13), and an overall end-to-end efficiency of 0.712(18) are simultaneously obtained.

Pure-water anion-exchange electrolysis is hindered by fragile ionomers and delaminating catalyst layers. Here, the authors report covalently anchoring catalysts within a cross-linked ionomer network, yielding a pure-water cell that delivers 2.55 A cm⁻² at 1.9 V and runs over 1,800 h.

Some small mRNA isoforms regulate cellular responses to stress. Here, Li et al. identify UFD1s, a stress responsive micro-RNA that encodes a conserved microprotein that regulates ubiquitination of full length UFD1, promotes autophagy and fatty acid oxidation, and acts to alleviate NASH progression in mice.

Exogenous iPSC-derived cells can activate endogenous cells to promote trabecular meshwork regeneration and restore aqueous humor outflow in glaucoma, providing insights into in situ regeneration, which may serve as an alternative to traditional cell therapy.

Monolithic Sn-Pb perovskite NIR imager with Sn(SCN)₂ passivation achieves low dark current, high detectivity and material recognition for advanced sensing and imaging.

Targeted degradation has the potential to treat diseases associated with pathological protein build up. Here, the authors report on an oligo-PROTAC which degrades FUS, a protein associated with frontotemporal dementia, demonstrating delivery on DNA nanoflowers for increase blood-brain barrier crossing and retention.

The crystallization mechanism at reduced dimensions remains poorly understood. Here, the authors use AFM and MD simulations to elucidate the nucleus-free crystallization of two-dimensional ice at atomic resolution.

Dihydrouridine (D) is an abundant RNA modification but its functions are currently unclear. Here, authors develop CRACI, a sensitive method for transcriptome-wide, single-base D mapping, identifying sites across mammalian and plant transcriptomes and identifying DUS2L as a mitochondrial D writer.

Fluorescence imaging and fluorescence recovery after photobleaching assays reveal that the mitochondrial nucleoid forms a suborganelle via liquid–liquid phase separation interactions between mitochondrial DNA and the mitochondrial transcriptional machinery.

Monitoring the diversity of viruses infecting animals is important for assessing zoonotic risk. Here, the authors use metatranscriptomics to characterise the viromes of small mammals, pangolins, and zoo animals in China to identify potentially zoonotic viruses.

Aryl thianthrenium salts are valuable in photocatalysis but traditionally require external electron donors for activation. Herein, the authors report an energy transfer strategy for the activation of aryl thianthrenium salts, eliminating the need for external donors.

Electrocatalytic CO₂ conversion offers opportunities for producing sustainable fuels and chemicals, but achieving strong performance with realistic CO₂ sources remains a challenge. Here a system is designed to use high-pressure captured CO₂, and achieves 85% Faradaic efficiency and high-purity C₂H₄ for over 1,500 h.

Designing monovalent anion-selective membranes is challenging due to the need to balance trade-offs between flux and selectivity, membrane stability, and cost-effective fabrication. Here, the authors synthesized a polymer via superacid polymerization and designed a membrane using in-situ interfacial polymerization to optimize membrane properties.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

The authors show that the endoplasmic reticulum-phagy receptor FAM134B interacts with SCAP to regulate cholesterol biosynthesis, sequestering SCAP when endoplasmic reticulum cholesterol is high but dissociating upon low cholesterol levels, allowing SCAP to activate cholesterol synthesis.

DNA double-strand breaks (DSBs), a highly deleterious form of DNA damage, are associated with multiple types of broken ends. Here, the authors identify a XRCC4-like factor that functions in the non-homologous end-joining DNA repair pathway to repair DSBs with complex broken ends.

Metal–support interfaces play a crucial role in dictating the catalytic behavior of heterogeneous systems. Here, the authors reveal a unique looping metal–support interaction in NiFe–Fe₃O₄ catalysts, where spatially separated yet coupled redox cycles boost hydrogen oxidation, providing new insights for the design of efficient heterogeneous catalysts.

Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.

Streptoseomycin is a potent antibiotic that contains a pentacyclic 5/14/10/6/6 ring system. Here, the authors report the enzymatic and non-enzymatic steps of the downstream modification of streptoseomycin biosynthesis and show a [6 + 4]-cycloaddition adduct as an unexpected biosynthetic intermediate.

Cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in Chinese Han and white British participants identify autosomal and X-chromosomal associations in more diverse populations.