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Pseudokinases are non-canonical protein-kinase-like proteins deficient in kinase activity, few of which have enzymatic activity that differs from phosphorylation. Now a pseudokinase-enabled cyclization activity for the biosynthesis of ribosomally synthesized and post-translationally modified peptides has been observed. Here pseudokinases can catalyse a Michael addition for (ene)thioether crosslinking through a sandwich-like substrate-assisted process.

Comparative analyses of rice centromeres from 70 high-quality genomes of the Oryza AA group provide insights into rice centromere evolution and genetic factors that shape these genomic regions.

A black phosphorus/Al₂O₃/black phosphorus heterostructure can be used to create a tunnel field-effect transistor in which the tunnelling current is in the transverse direction with respect to the drive current, leading to abrupt switching and a negative differential resistance with a peak-to-valley ratio of more than 100 at room temperature.

Yanqing Su, Wanmin Lin colleagues report the construction of an instance-based learning classifier by non-specific hybridization of DNA sequences both in simulation and in a small-scale experiment. The approach is simple, robust and scalable to larger classification applications.

Using siRNA screening, Chen et al demonstrate that Rab27a and its effector SYTL4 mediate the transport of influenza viral membrane proteins to the plasma membrane, highlighting their role in virion assembly and identifying SYTL4 as a potential therapeutic target for antiviral drug development.

Early detection of colorectal lesions is the cornerstone of cancer prevention. Intravenous administration of a novel fluorescent peptide probe now enables the screening of the whole colorectal area using near-infrared fluorescence colonoscopy, an approach that was documented as safe, well-tolerated and specific in its detection of colorectal polyps.

HARP are member of protein-only RNase P, which catalyzes pre-tRNA 5’-end processing and maturation. Here, the authors present crystal structure and provide mechanistic insights into pre-tRNA binding and cleavage by HARP proteins.

Fan and colleagues show that FLASH radiation promotes proinflammatory polarization of tumor-associated macrophages, which in turn increases T cell influx in medulloblastoma and synergizes with CAR-T cell therapy.

The likelihood of linking within a complex network is of importance to solve real-world problems, but it is challenging to predict. Sun et al. show that the link predictability limit can be well estimated by measuring the shortest compression length of a network without a need of prediction algorithm.

Previous, a long-term evolution experiment in E.coli resulted in spontaneous emergence of ecotypes that coexisted for more than 14,000 generations. Here, the authors show that the emergence and persistence of this phenomenon results from two interacting trade-offs, rooted in biochemical constraints.

The E. coli GTPase HflX promotes ribosomal-subunit dissociation by inducing conformational changes in central intersubunit bridges and thereby rescues stalled ribosomes under heat-shock conditions.

Huang et al. show that myocardial infarction (MI)-associated vasculature is structurally and functionally abnormal, impeding vessel function and cardiac repair in mice. Analyses of the transcriptome of the cardiac endothelium after MI identify a PDGF–NF-κB–HIF-1α Snail axis responsible for mesenchymal transformation of endothelial cells and show that genetic ablation or targeted disruption of PDGF signaling normalizes vasculature and improves cardiac function recovery after MI.

Fan and colleagues report that inhibition of PAK4 normalizes the tumor vascular microenvironment and sensitizes glioblastomas to CAR-T cell immunotherapy.

Su et al. find that BACH1 specifically interacts with the p53 (R175H) hotspot mutant. This has double oncogenic effects, leading to increased expression of the pro-metastatic targets of BACH1 as well as blockage of its capacity to activate ferroptosis.

Unilateral cross-incompatibility between certain varieties of maize prevents cross-fertilization and can facilitate hybrid breeding. Here the authors show that a PECTIN METHYLESTERASE gene is able to overcome this reproductive barrier and confer fertility when expressed in pollen of the male parent.

The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage.

Ribozymes that use the cellular cofactor S-adenosyl-l-methionine to methylate RNA remained elusive. Now, such a ribozyme is reported by identifying natural sequences that are active in vitro; and crystal structures of the ribozyme with and without the cofactor are determined.

Glioblastomas are generally resistant to treatment with immune checkpoint inhibitors. Here the authors show that IL6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune checkpoint blockade in preclinical models.

Polarization imaging can capture information from the scene that cannot directly be recorded by traditional intensity cameras. Here, authors demonstrate a single-shot full Stokes polarization camera incorporating a disordered metasurface array with weak dichroism.

The crystal structure of the full five-subunit BAM complex from Escherichia coli reveals the interactions between individual components and domains and provides insights into the biogenesis of β-barrel outer-membrane proteins.

Polycystic kidney disease 2-like 1 protein (PKD2L1) is a voltage-dependent calcium-dependent nonselective ion channel involved in sour taste perception and regulation of pH-dependent action potential of spinal cord neurons. Here the authors present the 3.4 Å cryo-EM structure of PKD2L1 in the open state and propose a model for the gating mechanism.

Fox and colleagues report that VEGF-A stimulation of endothelial cells induces the phosphorylation of profilin by VEGFR2 and Src. This regulation promotes endothelial cell migration and angiogenesis in mice facing pathological conditions such as tissue wounding and ischaemic injury.

Alkyne metathesis catalysts usually suffer from high moisture/air sensitivity, which limit their wide applicability. Here, the authors report efficient alkyne metathesis catalysts that can operate under open-air conditions with a broad functional group tolerance.

Resistance to anti-angiogenic therapies often occurs in patients. Here, the authors demonstrate the role of PDGF signaling in GBM resistance to anti-VEGF treatment via a mechanism that involves endothelial-mesenchymal transformation and transcriptional regulation of VEGFR-2.

Macrophages in the tumour microenvironment (TME) acquire tumour-promoting functions upon M2 polarization. Here the authors show, in a mouse model of glioblastoma, that endothelial cells in the TME induce macrophage M2 polarization via IL-6 and that depletion of endothelial IL-6 improves survival.

Fox and colleagues report that phosphorylation of profilin-1 in endothelial cells induces HIF-1α activation, leading to tumour angiogenesis in glioblastoma.

The molecular mechanisms underlying the regulation of dopamine transporter activity in the brain remain poorly understood. The authors show that glial cell line–derived neurotrophic factor, its receptor Ret and the Rho family GEF protein Vav2 are required for modulating dopamine transporter cell surface expression and transporter activity in the nucleus accumbens.

The article introduces a single chalcogenide glass fiber enables simultaneous and efficient sensing of body-surface temperature and sweat biomarkers for real-time physiological monitoring.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Crystal structures of M. tuberculosis elongation factors EF-Tu and EF-Ts in complex and GDP-bound Ef-Tu reveal the molecular basis of EF-Tu’s representative recycling and inactive forms in protein translation.