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Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

Drug tolerance to KRAS inhibition remains a major challenge in cancer therapy. Here the authors find that KRAS inhibition induces a cellular state characterized by enhanced ribosome biogenesis in KRAS-mutant colorectal cancer cells and these cells are vulnerable to inhibition of RNA polymerase I.

Evading infection in Cellulophaga baltica comes with cellular changes that alter carbon cycling, metabolite secretion and sedimentation rates.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

Preclinical studies indicate a synergistic effect of radiotherapy treatment (RT) and Immune checkpoint inhibitors (ICI) on tumor growth and metastasis. However, little is known about the immunomodulatory performance of different radioisotopes on the tumor microenvironment. Here, the authors employ alpha- versus beta-particle emitting radiopharmaceuticals in combination with dual ICI therapy and dissect mechanisms of in vivo immunomodulation and timing of ICI administration relative to RT, by comparing responses in immunogenic and non-immunogenic preclinical mouse models.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Engineered carbon nanotube sensors enable the detection of intracranial tumours in blood, identify low-abundance biomarkers and amplify cancer detection by capturing secreted factors from the entire tumour ecosystem for early-stage disease diagnosis.

Vaginal birth, exclusive breastfeeding and early contact with siblings promote colonization of the infant gut with bifidobacteria capable of producing aromatic lactates, a microbial and metabolite signal that is inversely related to the risk of allergen-specific sensitization and dermatitis later in life.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

LipoID profiles lipid droplet interactions and identifies interorganelle regulators.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

Gallrein et al. pair functional assays with clocks to compare chronological versus biological age of single neuron types in C. elegans, to probe their vulnerability or resilience to neurodegeneration, and use an in silico screen to identify neuroprotective drugs.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

A completely solid-state, single-chip, microwave-frequency surface acoustic wave phonon laser can generate coherent phonons from thermal noise or resonantly amplify injected phonons using only a direct current bias field.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Wakita et al. systematically compare the efficacy of 21 senolytics and identify a subpopulation of senolytic-resistant cells. They demonstrate a mitochondrial basis of senolytic resistance and show that metabolic interventions enhance senescent cell clearance in vivo.

The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19.

A computational method designs receptors called T-SenSERs, which have predictable signalling responses to tumour microenvironment soluble factors and can be co-expressed with conventional CARs in T cells to enhance their therapeutic activity.

Resistance noise in memristive devices is often described as a thermally activated process across simple energy barriers, but this can underestimate the role of entropy in a complex free energy landscape. Quantifying transition rates between discrete resistance states during resistance fluctuations in nanoscale GeTe shows that entropic contributions can strongly shape the free energy barriers.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, authors provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human myelodysplastic syndrome.

Telomeres are proposed to be sentinels for stress. Here, the authors report a strong induction of telomerase in space-flown Arabidopsis without telomere length changes. Instead, telomerase activity is inversely correlated with genome oxidation

Kletter et al. show that cell state-specific cytoplasmic density controls spindle architecture and scaling in neural differentiation, suggesting that the physical properties of the cytoplasm are a determinant in organelle size control.

The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

Bacterial ribonucleoprotein bodies are dynamic biomolecular condensates that play roles in RNA metabolism. Here, Ortiz-Rodríguez et al. show that, under stress, these condensates shift from a liquid state to a rigid state and switch their function from mRNA decay to mRNA storage, thus enabling transcript preservation and rapid recovery upon nutrient replenishment.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

The management of ulcerative colitis (UC) remains challenging due to the complexity of its etiology. Here, the authors establish that argininosuccinate synthetase 1 (ASS1) and its metabolite arginine are pivotal inducers of UC, through the triggering of mTOR and iNOS activation, and the induction of gut microbiota dysbiosis by metabolomics and proteomics. Inhibition of ASS1 by C-01 provides a viable strategy for the treatment of UC.

This study identifies key neurocognitive domains that distinguish patients with schizophrenia from healthy individuals using machine learning. Analyzing data from 1,304 participants, it demonstrates that verbal learning and emotion identification effectively classify conditions, promoting efficient neurocognitive profiling strategies.

Researchers discovered five phases of brain rewiring across the lifespan. The eras of childhood, adolescence, adulthood, early aging, and late aging each have characteristic rewiring of structural connections across the whole brain.

Here, using murine models of prostate cancer, the authors show that reduced fecal microbiota alpha-diversity correlates with increased prostate tumor burden, and that Omega-3 prebiotic supplementation reduces prostate cancer up-grading associated with a reduction of gut Ruminococcaceae and fecal butyrate levels.

A recombinant adeno-associated virus system for restricted gene expression in brain endothelial cells enables cerebrovascular disease modelling.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

The authors describe a mechanism for the clearance of macromolecules from cerebrospinal fluid in which macromolecules traverse from periarterial to perivenous spaces, at sites where intersecting leptomeningeal perivascular (arteriovenous) spaces overlap.

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.

Myb1 functions as a switch-like regulator of state transitions in Hortaea werneckii, whereby its expression and degradation are coupled to nutrient conditions, stabilizing unicellular or multicellular growth.

The role of cortical PV neurons in the regulation of sleep architecture and homeostatic sleep rebound is not fully understood. Here, the authors show that CaMKII-mediated control of cortical parvalbumin-neuron activity regulates the homeostatic sleep rebound in mice.