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Macrocyclization typically proceeds via thioesterase mediation in type I polyketide synthases. Now, using genome mining and crystallographic analysis, an alternative mechanism for stereoselective macrocyclization in the akaeolide biosynthetic pathway is reported. The mechanism is proposed to proceed via an iminium-catalysed tandem Michael addition and Knoevenagel condensation, using nuclear transport factor 2-like enzymes.

This study achieves precise atomic-scale control over ferroelectric polymer chains through facet modulation, significantly enhancing ferroelectric phase stability, thereby enabling efficient and tunable multiband electromagnetic attenuation.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

Here they show that NONO collaborates with HOXA1 to modulate gene expression during early cardiomyocyte differentiation. This interaction facilitates activation of the Wnt signaling pathway, establishing the NONO-HOXA1-Wnt axis as a key mechanism in cardiac development.

Reconciling broad substrate generality with high enantioselectivity remains a core limitation of enantioselective catalysis. In this study, the authors design a new-to-nature photoenzyme that unlocks enzymatic deracemization of structurally diverse allenes, an entropically disfavored process inaccessible to natural biocatalysts.

The structure of layered oxides dictates their properties as positive electrodes in sodium-ion batteries, but its rational design remains challenging. Here, authors employ electronegativity and configurational entropy as a design descriptor to guide the synthesis of a sodium-deficient layered oxide with an O3 stacking sequence, rendering good thermal and air stability.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

Optogenetic manipulation of spindle dynamics reveals that microtubule shortening at kinetochores limits spindle elongation rather than moving chromosomes, revealing local chromosome–spindle interactions.

The simultaneous construction of two constitutionally distinct stereogenic centers at remote positions in a single asymmetric catalytic step remains scarce, owing to the lack of reliable models for distant stereochemical induction for both chiral entities. Herein, the authors report an electrochemical cobalt-catalyzed asymmetric hydroacylation of enynes by a desymmetrization strategy that enables the enantio- and diastereo-selective construction of remote dual stereocenters.

Light-driven enzymatic catalysis has enabled important abiological transformations in vitro. Now a cellular ene-reductase photoenzyme is integrated with a de novo-designed olefin biosynthetic pathway for photoinduced hydroalkylation, hydroamination and hydrosulfonylation reactions within cells.

Here, the authors develop AMPLiT a tool for screening antimicrobial peptides in metagenomic datasets, and apply it to human coprolite metagenomes, finding that Segatella copri, an ancient prevalent human gut bacterium declined in modern populations, harbors unexplored antimicrobial reservoir, offering an alternative approach against modern pathogenic infections.

Several genes in regulating flowering time have been identified in soybean, but the epigenetic regulators are still largely unknown. Here, the authors identify GmLDL2, a histone H3K4me1/2 demethylase, as a crucial flowering time regulator in soybean.

LINE-1 retrotransposons are implicated in aging, but their role in cardiac aging specifically is not well understood. Here the authors show that LINE-1 expression rises in mouse hearts with age. Genetic LINE-1 derepression is accompanied by cGAS–STING activation and cardiac dysfunction, while pharmacological inhibition of LINE-1 or STING improves cardiac function in aged mice.

The efficiency of perovskite/Cu(In,Ga)Se₂ tandem solar cells is limited by halide segregation in the perovskite layer. Zhang et al. use 2-pyrrolidinone to slow the crystallization of halide intermediates, ensuring a homogeneous distribution and achieving a power conversion efficiency of 27.3%.

MAPLE is a pairwise-learning framework for reliable and privacy-preserving prediction of epigenetic age and disease risk, helping advance methylation-based health assessment.

SpatialZ generates virtual single-cell spatial transcriptomics slices between experimentally measured sections, enabling accurate and efficient building of 3D cell atlases of different tissues.

Cryo-electron microscopy structures of three large ornate natural bacterial RNA molecules reveal their quaternary structures and intra- and intermolecular interactions that stabilize them.

Traditional nanopore sensors use barrel-shaped protein channels. Here, the authors report on a study into the use of globular protein, ferritin, as a nanopore sensor, demonstrating membrane insertion and sensor application, showing the potential of non-barrel-shaped proteins for nanopore sensing.

Achieving photo-thermal stability and device operational stability of tin-lead perovskite solar cells remains a major challenge. Here, authors replace tin fluoride additive by lead powders followed by lead fluoride post-treatment, achieving efficiency of 24.07% in stable tin fluoride-free devices.

Colourful patterns in two-dimensional lead halide perovskites are created by letting them self-etch into tiny squares that can template epitaxial growth.

Elevated adipocyte-derived AFABP in obesity disrupts iron homeostasis in intestinal stem cells (ISCs), which impairs PPARα signalling and blocks ISC differentiation after injury.

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.

Controllable and scalable phase transition of transition metal chalcogenides is challenging. Using in situ microscopic analysis, a non-stoichiometric phase transition from PdTe₂ to PdTe is observed on the atomic scale, providing mechanistic insights into the scalable phase engineering of transition metal chalcogenide films and heterostructures.

Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

The efficient low-temperature combustion of stable alkanes remains a major challenge in catalysis. Now it has been shown that a Pt–Nb dual-atom catalyst enables propane combustion through a distinct stepwise-boosting, current-assisted atomic relay mechanism, yielding complete conversion below 200 °C and a high turnover frequency.

This study reports that genomic signatures composed of the loss of pluripotency inhibitors, expansion of pluripotency activators and maintenance of an epigenetically permissive state contribute to the plantlet formation in Kalanchoe.

Psychological stress-mediated dysregulation of catecholamine signalling rewires the hepatic kynurenine pathway, which in turn impairs liver CD8⁺ T cell function and promotes liver cancer progression.

Metabolic syndrome (MS) is associated with enhanced risk to develop endometrial cancer (EC). Here, the authors show that oleic acid, increased in MS, promotes endometrial cancer by supporting the stability of the rate-limiting enzyme in polyamine metabolism ODC1 and polyamine accumulation.

Seed size plays an important role in determining soybean yield. Here, the authors report GmSW17, encoding a homolog of Arabidopsis UBP22 that plays a role in deubiquitination, as a positive regulator of soybean seed width and seed weight through inhibition of the G1-to-S transition by interacting with GmSGF11 and GmENY2.

A new architecture based on high-valence sulfur/sulfur tetrachloride cathode chemistry is described for manufacturing high-voltage anode-free sodium–sulfur batteries, demonstrating promise for applications in grid energy storage and wearable electronics.

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.

Lactate fuels cancer growth by activating ERK signaling through GCN5-mediated lactylation of ERK, which disrupts ERK–MEK interactions. Development of a cell-penetrating peptide blocking lactylation slows KRAS-mutant tumor development.

Alphaherpesvirus infections pose a health challenge due to the lack of effective broad-spectrum antiviral strategies. Here, the authors identify a broadly neutralizing antibody, 16F9, which targets glycoprotein B, offering cross-protection against multiple viruses and demonstrating robust efficacy in mouse models, paving the way for antiviral interventions.

Qian and colleagues show that IL-17REL functions as a decoy receptor to suppress the effects of IL-17 family cytokines and reduce intestinal inflammation.

Mechanisms confer to the enhanced cold tolerance in japonica rice have not been fully elucidated. Here, the authors report a homeodomain-leucine zipper (HD-Zip) I transcription factor encode gene CTB5 is responsible for japonica rice cold tolerance by interacting with genes in gibberellin and abscisic acid pathways.

Si, Dong, Xing and colleagues present ReTagX, a bright and compact array tag that restores photobleached signals via reversible and fluorogenic labelling, enabling long-term and high-resolution imaging of protein dynamics in living cells.

A DNA nanoruler platform enables precise measurement of the labeling radii of TurboID and APEX2, uncovering their contact-dependent mechanisms. These findings redefine the enzymology of proximity labeling and highlight the promise of DNA nanotechnology for spatially resolving enzyme reactivity with nanometer precision.

Ubiquitin tagging controls protein fate, but how the COP1-DET1 E3 ligase works was unclear. Here, the authors present cryo-EM structures of an inactive stacked assembly that switches to an active dimer on substrate binding, with DET1 guiding enzymes to start and co-workers to extend ubiquitin chains.

Chen et al. report the design and characterization of a systemically injectable oncolytic virus with tumor-targeting and low-immunogenic properties, engineered to induce tumor cell pyroptosis under local mild hyperthermia.

A microwave-assisted process is developed for the rapid and scalable manufacture of pure-phase metallic MoS₂ nanosheets, enabling practical electrochemical devices for energy applications.

YTHDC2 is a promising therapeutic target, but lacks potent inhibitors. Yang et al. develop a deep learning-based molecule generator EPMolGen. Using this model, they discover a potent, selective, and cell-active small molecule inhibitor of YTHDC2.

Organic electrochemical neuron sensors enable rapid, energy-efficient neural signal detection and modulation, supporting closed-loop neuromodulation and offering a promising platform for implantable neurotherapeutic applications.

Bioactive sesquiterpenes accumulating in petunia stigmas are synthesized in the floral tube and then transported to the pistil via natural fumigation within the internal airspace of the developing flower.

Molecular mimicry between a gut commensal and a tumour antigen forms part of an important mechanistic framework that can boost the efficacy of immune checkpoint blockade therapy and restrain tumour growth.

Here the authors report that genetic or pharmacological inhibition of phosphoglycerate kinase 1, an enzyme involved in glycolysis, attenuates acute kidney injury in mouse models of acute kidney injury via inhibition of ferroptosis.

Labdane derived hapmnioide-type diterpenoids, which have been identified as chemical markers for Haplomitrium liverwort, show potent anti-inflammatory and allelopathic activities. Here, the authors report the total synthesis of seven typical Haplomitrium diterpenoids through late-stage biomimetic skeletal reorganization.

Sluggish interfacial charge transfer in Li-metal batteries limits ultrafast charging and causes side reactions. The authors design solvent molecules to enhance Li⁺ coordination, improving the charge-transfer kinetics and enabling stable high-rate cycling of Li-metal cells.

Wastewater treatment plants harbour extensive but poorly characterized microbial genetic diversity. Using 828 metagenomes from wastewater treatement plants globally, this study reconstructs >24,000 metagenome-assembled genomes, including >12,000 new species, providing a genome-resolved framework for understanding and engineering activated sludge functions.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.