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Azetidine is a pharmacophore present in drug-related molecules. Here the authors unveil a two-metalloenzyme cascade leading to the azetidine-containing polyoximic acid, in which PolE functions as an Fe²⁺/pterin-dependent l-isoleucine desaturase, while PolF is a haem-oxygenase-like diiron oxidase, orchestrating the sequential desaturation and cyclization. These findings expand our knowledge of metalloenzymes.

Nuclear architecture depends on proper regulation of lamin A/C modifications. Here, the authors show that TAF4A and NF-Y control Kansl2 expression in muscle stem cells, preserving genome stability and supporting muscle regeneration.

Authors present a bispecific antiviral design targeting the virus and the host that simultaneously offers broad-spectrum protection against multiple existing transmissible human-pathogenic coronaviruses, including the Paxlovid-resistant SARS-CoV-2 mutants.

Shabanzadeh et al. identify and validate a pathway whereby RGMa cleavage by SKI-1 modifies gene expression related to blood–brain barrier (BBB) integrity after stroke. SKI-1 inhibition restores BBB integrity and neuronal function in mouse and rabbit stroke models.

Dengue virus transmission by Ae. aegypti mosquitoes poses a significant public health threat, necessitating innovative control strategies. Here, the authors demonstrate that, while successive blood feeding increases earlier dengue virus dissemination, the inhibitory effects of Wolbachia remain strong, highlighting Wolbachia’s potential to disrupt dengue transmission under natural feeding conditions.

Legionella effector LtpM is found to recognize short two-residue sequons, enabling site-specific O-glucosylation with minimal perturbations to a target protein, and is used to show that O-glucose can act as a constitutively active O-linked N-acetylglucosamine mimic.

Electrosynthesis of n-propanol from CO has been limited by poor selectivity and low product concentration. Here a Sn–Cu catalyst/carbon/ionomer heterojunction is prepared where the adjacent atomic active sites favour the coupling of C₁ and C₂ intermediates to C₃ product with 47% Faradaic efficiency and the reversal of electro-osmotic drag concentrates the product to 30 wt%.

Myoglobin (Mb) is the critical pathogenic factor for Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI). Here, the authors show that anti-Mb RabMAb injection blocking the passage of free Mb through the glomerular filtration barrier significantly rescues both homologous and heterologous RM/CS-AKI animal models.

Heat pumping is in high demand at cryogenic temperature, but whether thermoelectricity can take on cryogenic heat pumping is an open question. Here, the authors answer this question by leveraging bipolar effect to enhance transverse thermoelectricity in semimetal Mg₂Pb for cryogenic heat pumping.

Conventional structure-based drug design pipeline is a complex, human-engineered process with multiple independently optimized steps. Here, the authors report a sequence-to-drug concept that discovers drug-like small molecule modulators directly from protein sequences.

The authors report the large low-field-driven electrocaloric effect in the novel organic-inorganic hybrid TMCM-CdCl₃, underlyingly from the disordering of organic cations and the low-symmetry interaction induced two-step meta-electric transition.

Long non-coding RNAs regulate developmental transitions and stress responses in plants. Here Zhao et al. show that a non-coding antisense transcript MAS transcribed from the Arabidopsis MAF4 locus activates H3K4me3 deposition and MAF4 transcription to suppress precocious flowering.

Aberrant RNAs are recognized by the RNA helicase MTR4 and degraded by the RNA exosome complex. Here the authors show that the MTR4/hnRNPK complex destabilizes defective RNAs terminated in introns, termed 3XTs.

Excessive inflammatory responses contribute to severe malaria. Here, Du et al, show that the protein tyrosine phosphatase PRL2 contributes to neutrophil activation and extracellular trap release in an experimental model of severe malaria.

SynGAP and PSD-95 are two abundant proteins that form a complex and undergo liquid–liquid phase separation (LLPS) in the postsynaptic density of neurons. Now, O-GlcNAcylation of SynGAP has been found to suppress LLPS of the SynGAP/PSD-95 complex, and O-GlcNAc-dependent LLPS was also shown to be dynamically regulated by the enzymes O-GlcNAc transferase and O-GlcNAcase.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Limitations in performance and stability of organic electrochemical transistors hinder their application in biosignal amplification. Here, the authors show that high-spin, hydrophilic conjugated polymers exhibit ambipolar charge transport properties and can capture and amplify diverse electrophysiological signals.

Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs.

Sea cucumbers are predominant deposit feeders in benthic ecosystems. This study elucidates the mechanisms within the sea cucumber digestive system and their symbiotic microbiome which enable them to efficiently utilize nutrients from seabed sediments.

Cryo-EM structures of complement receptors C3aR and C5aR1 bound to their respective anaphylatoxin ligands C3a and C5a reveal insights into the conserved features and topological diversities of C3aR and C5aR1 in recognizing C3a and C5a.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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

Epigallocatechin gallate (EGCG) is a catechin flavonoid which induces apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Here authors use an interdisciplinary approach to show a direct interaction between EGCG and the tumor suppressor p53 and demonstrate that EGCG inhibits ubiquitination of p53 by MDM2.

The SPT-ORMDL complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here, the authors elucidate the molecular basis of ceramide sensing by the human SPTORMDL complex for establishing sphingolipid homeostasis.

Here, the authors engineer microbial production of muscle titin fibers with highly desirable mechanical properties and provide structural analyses that explain the molecular mechanisms underlying high performance of this polymer with potential uses in biomedicine and textile industries, among others.

The rational design of PROTACs is difficult due to their obscure structure-activity relationship. Here the authors present a deep neural network model - DeepPROTACs - for predicting the degradation capacity of a proposed PROTAC molecule.

Utrophin is a dystrophin-related protein stabilizing the sarcolemma in absence of dystrophin. Here the authors report that inactivation of the protein deacetylase SIRT6, involved in the deacetylation of the epigenetic mark H3K56ac in muscle cells, increases expression of utrophin and ameliorates dystrophic muscle pathology in mice.

A phenylboronic acid-modified hetero-octameric Mycobacterium smegmatis porin A nanopore can directly distinguish 11 types of nucleoside monophosphates with a 0.996 accuracy.

T cells compose a critical component of the immune response to coronavirus infection with SARS-CoV-2. Here the authors characterise the T cell response to SARS CoV-2 in patients and their close contacts, and show the presence of SARS-CoV-2 specific T cells in the absence of detectable virus infection.

Using a behaviorally obtained reference point to compute social value, Ma et al. show that social-value distance is encoded by the amygdala in prosocials. Oxytocin amplifies this amygdala representation and increases prosociality in individualists.

The efficacy of cancer radio-immunotherapy is limited by the immunosuppressive tumor microenvironment. Here the authors report fusogenic liposomes loaded with Auranofin, a gold containing drug approved for rheumatoid arthritis, multivariate-gated aptamer assemblies and PD-L1 aptamers, as an adjuvant for melanoma-targeted radio-immunotherapy.

Observation of a new resonance in the 19-fluorine to 20-neon thermonuclear reaction at the China JinPing Underground Laboratory (over 2 km below ground) may provide clues to observed discrepancies in calcium production in the evolution of the first stars.

Suppression of transcription in S-phase is crucial to prevent genome instability. Zhang et al demonstrate that increase of H4K20me1 due to loss of Kmt5b cause genome instability in muscle stem cells, resulting in stem cell senescence but rhabdomyosarcoma formation when p53 is inactivated.

The RXFP1 relaxin receptor is a critical mediator of physiological adaptation to pregnancy and an emerging drug target. RXFP1 activation was found to entail an unexpected mechanism of ectodomain disinhibition resulting in downstream signaling.

Targeted proteomics enables robust hypothesis-driven research. Here, Yu et al. present a multiplexed approach for targeted pathway proteomics and apply it to quantify protein families across 480 fully genotyped Diversity Outbred mice, revealing impacts of genetic variation on protein expression and lipid metabolism.

A broad boost to dryland vegetation productivity due to the CO2 fertilization effect is negated by climate changes in at most 4% of global drylands, resulting in desertification, according to analysis of climate and vegetation datasets.

Global in situ observations show greenhouse gas emissions from wetlands are lowest when the water table is near the surface, and therefore rewetting wetlands could substantially reduce future emissions.

Advances in our ability to manipulate genetics leads to deeper understanding of biological systems. In this perspective, the authors argue that synthetic genomics facilitates complex modifications that open up new areas of research.

A recent study using genomic modelling has uncovered the complex population history of wheat in the Holocene, identified convergent adaptation during bread wheat’s spread across Eurasia and predicted future population decline of its key relatives.

Metastatic disease is the major reason for breast cancer-related deaths; therefore, a better understanding of this process and its players is needed. Here the authors report the role of SIRT7 in inhibiting SMAD4-mediated breast cancer metastasis providing a possible therapeutic avenue.

From 2002 to 2021, about 64% of land precipitation contributed to terrestrial water storage, highlighting the intricate relationship between precipitation, land surface processes, and climate change, according to analysis of satellite geodesy observations and a new metric to quantify the transformation of precipitation into terrestrial water storage.

This Registered Report describes an extensive comparison of 22 near-infrared fluorescent proteins in vitro, in cultured mammalian cells, and in model animals, clarifying top performers in diverse biological settings.

Metagenomic analysis reveals distinctive multi-kingdom species, functional signatures and bacteria-fungi interactions pattern between excess body weight CRC and lean CRC in gut microbiome, which contribute to precision medicine of CRC.