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In this study, using a combination of quantitative biochemical assays and fluorescence microscopy, the authors demonstrate that a fraction of free extracellular mitochondria can enter recipient cells through macropinocytosis. Once internalized, mitochondria are able to escape from endosomal compartments into the cytosol, where they may integrate into the endogenous mitochondrial network.

Resistance mutations in BCL-2 reduce the clinical efficacy of venetoclax. DeAngelo et al. show stapled BAD BH3 peptides can retain and even enhance binding to these mutants, offering a structurally informed strategy to overcome this mechanism of cancer drug resistance.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

Multiblock oxygenated polyols often show better properties than the constituent polyols, but their synthesis can be complex and difficult. Here a switchable catalysis concept is described which allows for the efficient preparation of multiblock poly(ether-b-ester) materials starting from mixtures of common monomers.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Self-assembly of block-copolymers yields nanoscale structures in a facile way, but the diversity of structures is limited. Here, the authors demonstrate how block copolymer layering can be used to access new non-equilibrium morphologies.

Molecules can self-assemble to form ordered phases with defined shape and periodicity, but there are a limited set of morphologies reported. Here, the authors have manipulated block copolymer thin films via an iterative assembly process to form a diverse library of morphologies.

Double-gyroid networks assemble in diverse soft materials, yet the molecular packing that underlies their complex structure remains obscure. Here, authors advance a theory that resolves a long-standing puzzle about their formation in block copolymers.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

Slice-and-view scanning electron microscopy tomography is used to characterize a double-gyroid block copolymer, finding mesoatomic distortions that break the symmetry of these soft-matter crystals across multiple scales.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Simple routes to self-assembling magnetic materials are elusive. Tew and colleagues produce copolymers containing cobalt complexes, which phase separate to give ferromagnetic properties at room temperature following heat treatment.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

In a silent trial involving 197 patients with lung cancer over a span of 4 months, a fine-tuned pathology foundation model was able to identify the presence of EGFR mutations with high accuracy, potentially preventing further genetic testing in 43% of cases.

The accuracy of single-cell sequencing can be hampered by the occurrence of doublets, where two or more cells are sequenced together, thus leading to data misinterpretation. Here, the authors present ImageDoubler, an image-based algorithm for detecting doublets and missing samples in single-cell sequencing.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Profiling assays measure thousands of features to uncover biological insights but lack reliable methods for quality evaluation. Here, the authors develop a versatile information retrieval framework to robustly quantify sample activity and similarity in large-scale profiling data.

A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a promising candidate for tuberculosis treatment regimens.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Artis and colleagues show that enteric neurons produce CGRP-related ADM2 to promote intestinal tissue-protective functions in ILC2s.

Cas9 DNA targeting is inherently sequence specific but not temporally controlled. Here, authors spatiotemporally couple Cas9 activity to target site transcription in eukaryotes and exploit this to preferentially edit the more highly transcribed of two alleles that harbor identical Cas9 targets.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

Distal gene regulation is increasingly recognised as a major contributor to complex trait variability. Here, the authors show that a heritable, biologically interpretable transcriptome signature driven by distal regulation predicts metabolic traits across mice and humans.

Nodelman, Folkwein et al. define a regulatory region in Chd1 containing adjacent inhibitor and activator elements that compete for binding to the remodeler ATPase. The competition between these elements shows how remodeler regulation is integrated into the nucleosome sliding cycle.

Baculoviruses are large DNA virus widely used as biotechnological tools. Here, authors present the complete cryoEM structure of a circulating nucleocapsid, including the DNA packaging and exiting hub termed the apical cap.

Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

The let-7 microRNA has been implicated in development and disease. Its expression must thus be tightly regulated, and previously uridylation and Lin28 were implicated in let-7 stability. Zcchc11 is now shown to be the uridylase that mediates pre–let-7 modification and regulates mature let-7 levels and activity in mouse embryonic stem cells.

Graphene–quantum dots on CMOS sensor offers broadband imaging.