Search

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Schober and colleagues show that effector CD8⁺ T cells undergo metabolic shutdown, CD8⁺ central memory T cells are the most metabolically active, and naive-like memory T cells are quiescent during the acute phase of the immune response and represent the dominant population of memory CD8⁺ T cells after yellow fever vaccination in humans.

The DNA-dependent protease SPRTN cleaves toxic DNA-protein crosslinks (DPCs). Here, the authors show that SPRTN is activated by DPC-ubiquitylation through an allosteric ubiquitin binding interface. This regulatory mechanism enables precise control of SPRTN activity during DNA repair.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

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.

RNA oxidation is poorly characterized. Here, the authors introduce OAbSeq, a sequencing method that maps oxidized sites at nucleotide resolution and show guanosine oxidation proceeds via transient oxo8G to produce mainly abasic sites.

A mode of bidirectional microglia–neuron crosstalk through Hex–GM2–MGL2 and centred around GM2 ganglioside turnover is essential for homeostatic regulation of central nervous system membrane components.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Roßmann and colleagues report a simple strategy to generate a panel of fluorescent HaloTag Ligands that enable visualisation of cell surface proteins at low concentrations and with brief incubation times. They use these probes to label neuromodulatory receptors in neurons, allowing for the distinction of surface versus internal receptors of the presynaptic terminal.

Sepsis causes endothelial dysfunction that drives vascular failure and organ injury. Here the authors show that neutralizing truncated procalcitonin reduced pro-inflammatory activation and leakage in the endothelium, resulting in preserved organ integrity, improved clinical outcomes and predicted survival in septic mice.

Neutrophils can release S100A8/S100A9 as an alarmin via gasdermin D pores. Here, the authors untangle the regulatory mechanisms driving this pathway and show that active repair processes make these pores transient, which can prevent the usual lytic cell death.

In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Methylthio-alkane reductases are recently discovered enzymes that can produce methanethiol and small hydrocarbons from methylated sulfur compounds. Now the cryo-EM structure of a methylthio-alkane reductase complex is solved, revealing large metalloclusters previously observed only within nitrogenases.

Growing demand for robust plasma and serum proteomics highlights the need for better standardization. Here, the authors introduce an open 211-peptide internal standard that enables consistent quantification, cross-platform alignment and clinical utility across serum and plasma studies.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

A molecular mechanism is revealed through which commensal bacteria modulate intestinal epithelial barrier function.

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.

The study combines bulk, single-cell, and spatial transcriptomics of human carotid plaques. It identifies immune– stromal cell diversity, spatial macrophage gradients, smooth muscle cell heterogeneity, and morphology-defined plaque subtypes.

Kao et al. provide insight into the metabolic requirements of IL-17A-producing γδ T cells, offering an actionable target to treat psoriasis by inhibiting fatty acid synthesis.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

MRP8/14 are actively secreted by myeloid cells during inflammation. Here the authors show that MRP8/14 play an important role in leukocyte recruitment to the inflammatory site, triggering an autocrine cascade that promotes neutrophil adhesion to the endothelium.

Import of proteins into specific cellular compartments is critical for organelle function and several proteins are known to be imported into multiple compartments. Here, the authors report that the protein Ptc5 is first sorted to and processed in the mitochondria before being targeted to peroxisomes, which may influence mitochondria-peroxisome interorganellar contact.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Coating technologies call for effective methods capable of suppressing the coffee-ring effect for a uniform particle deposition. Rey et al. show homogeneous drying patterns can be achieved via physically adsorbing polymers onto particle surfaces and the method is applicable to a wide range of materials regardless of the shape of the dispersed particles.

The epigenetic and transcriptional roles of Nucleoporin 98 (NUP98) fusion oncoproteins in driving pediatric acute myeloid leukemia (AML) remain to be explored. Here, the authors identify a core set of genes regulated by NUP98::KDM5A and suggest CDK12 as a potential therapeutic vulnerability.

Microbial decomposition of plant litter initially increases the molecular diversity of dissolved organic matter, but prolonged microbial recycling diminishes this diversity, highlighting how microbial metabolism influences soil carbon turnover.

Fibro-calcific aortic valve disease is closely interlinked with dyslipidemia. Here, the authors used quantitative lipidomics to profile the metabolic trajectories in human aortic valves, and found that male and female patients manifest markedly different lipid signatures of disease progression.

Metabolic interactions shape ecosystems but remain hard to study. Here, authors present MetaFlowTrain, a modular, low-cost fluidic system controlling metabolic fluxes between microbes, and show its value in uncovering soil conditioning, microbial interactions, and exometabolite-driven inhibition.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

A combination of gentle stimulated emission depletion microscopy imaging and deep-learning-based improvements in signal-to-noise ratio enables high-resolution reconstruction of neuronal architecture in living tissue.

Design of efficient catalysts requires understanding the decisive electronic parameters for catalytic efficacy and their dependence on elemental composition. Here, the authors report covalency as suitable descriptor of perovskite-type transition metal oxides as chemo-catalysts.

The mechanism of calcium carbonate formation has been of interest for decades, but additive-controlled systems are poorly understood. Here the authors show that polycarboxylates facilitate bicarbonate entrapment and thereby inhibit nucleation. Distinct water environments in amorphous calcium carbonate nanoparticles arise from colloidal formation pathways and lead to mineral conductivity.

Some transcription factors can organize into different structural states, from small nanoscale clusters to macrophases. Here authors show that NHA9 undergoes differential conformational expansion across these states and exhibits micelle-like organization with non-fixed stoichiometry.

Whether there is an exception to the homogenous wiring rule in visual systems remain largely unknown. Here authors reveal heterogeneity in the synaptic connectivity of cell types in the fly eye. Thus, parallel units of the eye will compute the same visual input differently.

tRNA modifications are essential for function, yet their timing relative to processing is unclear. Here, the authors show that queuosine and derivative modifications occur before splicing of pre-tRNA^Tyr, with cryo-EM confirming direct recognition by the QTRT1/2 complex.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.

Beck et al. conducted single-cell and spatial profiling of embryonal tumors with multilayered rosettes, finding that malignant cellular hierarchies are driven by developmental programs and specific members of the chromosome 19 microRNA cluster.

Certain bovine antibodies have ultra-long long complementarity-determining regions (CDRs) that contain a knob for antigen interaction, which is connected to the antibody through a stalk. Here, the authors combine biophysical experiments and MD simulations and show that the stalk length is critical for the folding and stability of these antibodies. The authors also demonstrate that ultra-long bovine CDRs can be grafted into human antibodies, and furthermore show that de novo designed mini-domains that bind to the SARS-CoV-2 spike protein with high affinity can be integrated as a knob in ultra-long CDRs in bovine and human antibodies, which neutralize SARS-CoV-2.

Attenuating effects of the ketogenic diet on colorectal cancer (CRC) cell growth has been previously described. Here, using a mouse model of CRC with a humanized microbiome, the authors identify a shift toward gut bacterial species that produce stearic acid in ketogenic conditions, resulting in elevated levels of free stearate in the gut lumen, which they then show exhibits tumor-suppressing properties.

Bcl-3 modulates effector T cell responses, but the importance of Bcl-3 in T regulatory cells and autoimmunity is not clear. Here the authors show that Bcl-3 impedes NF-κB DNA binding to alter T regulatory cell development and function, causing spontaneous colitis in mice.

Here, the authors present the crystal structure of Transportin 3 (TNPO3) bound to its cargo cold-inducible RNA-binding protein (CIRBP), uncovering a distinct mechanism of protein nuclear import regulation independent of phosphorylation.

Root microorganisms can trigger the release of immune-stimulating N-hydroxypipecolic acid from Arabidopsis roots by manipulating a standby circuit of its continuous synthesis and immobilization. N-hydroxypipecolic acid thereby influences shoot growth and pathogen defence.

Cellular senescence plays a crucial role in cancer therapy, influencing how tumours respond to treatment. Here, the authors show that therapy-induced senescence in B-cell lymphoma leads to myeloid-like plasticity, enhancing T-cell recognition and improving patient outcomes.