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MitoCatch is a cell-type-specific mitochondrion-targeting system that links mitochondria and the cell surface by protein binders and delivers mitochondria into the target cell.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

DNA damage burden and inadequate repair in CUX2⁺ cortical layer 2/3 excitatory neurons contributes to selective vulnerability in neuroinflammatory injury.

A small molecule, CLEO4-88, was identified that acts as a molecular glue, linking the E3 ligase subunit GID4 with ACAA1. Instead of triggering ACAA1 degradation, the compound inhibits its enzymatic activity.

The mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

Myopathy caused by BAG3 mutation disrupts muscle protein homeostasis and leads to severe muscle weakness. In mouse models, the authors demonstrate that impaired autophagy drives the pathology, while gene therapy targeting the mutated BAG3 improves muscle function.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.

N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.

Here, the authors conduct a metagenomic-based study of England’s rivers to show that biofilm bacteria are taxonomically and functionally diverse and are key to biogeochemical cycling, highlighting the importance of river biofilm bacteria in understanding and monitoring freshwater ecosystem health.

MoCox6 is an inner mitochondrial membrane regulator of mitophagy in Magnaporthe oryzae, and targeting it with a small molecule, Pan-RAS-IN-1, suppresses fungal virulence and reduces rice blast disease.

Small cell lung cancer (SCLC) cells show inherently low antioxidant defenses, making them prone to lethal oxidative stress induced by thioredoxin reductase 1 (TXNRD1) inhibitors. Here, authors demonstrate that activating NRF2 mediated tissue protection allows increased therapeutic dose of TXNRD1 inhibitors to enhances SCLC cell killing in vivo without added toxicity to healthy tissues.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Using single-cell tissue imaging and spatial proteomics to study mitochondria–lipid droplet coupling in hepatocytes, PLIN5 phosphorylation is identified as a mediator of lipid flux and nutrient stress responses.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

Paracrine signalling between tuft cells and enterochromaffin cells is a key mode of immune–sensory and gut–brain communication, and accounts for the pattern of gastrointestinal symptoms that occurs during parasite infections.

Antisense oligonucleotides (ASOs) are used in research and therapy. Here, the authors show that PS-modified ASOs bind key DNA repair enzymes and form nuclear condensates that dysregulate the DNA damage response, disrupt DNA repair, and cause toxic DNA lesions, revealing mechanisms underlying ASO-induced toxicity.

Regulatory DNA screens often lack nucleotide-level resolution. Here, authors present an end-to-end CRISPR base-editing and sequencing framework that maps regulatory variants at single-nucleotide resolution, revealing enhancer mutations that alter CD19 expression and enable CAR-T therapy resistance.

AhR functions as a neuronal brake on axon regeneration, integrating environmental sensing, protein homeostasis and metabolic signalling to control the balance between stress adaptation and axonal repair.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

A new cerebrospinal fluid biomarker, AcTau174, was elevated in frontotemporal lobar degeneration with TAR DNA-binding protein (FTLD-TDP), distinguishing this pathology from FTLD-Tau, and was associated with disease severity and progression in FTLD-TDP.

The susceptibility of mouse and human T cells to ferroptosis is determined by the balance of systemic polyunsaturated and monounsaturated fatty acids, highlighting a key role for lipid metabolism and dietary composition in regulating T cell function.

Two distinct types of atomic insulator can be distinguished by the distribution of charges within the unit cell. Now, real-space imaging of WSe₂ shows that it is a so-called obstructed insulator.

The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

Insights into the mechanism by which phosphatidylserine functions as a non-classical inhibitory molecule during T cell exhaustion, and how phosphatidylserine-targeting antibodies enhance T cell responses are explored.

Kroczek et al show that degradation of DNAJC15 by OMA1 and AFG3L2 under stress limits mitochondrial protein import and OXPHOS biogenesis. Non-imported proteins lead to the induction of the unfolded protein responses from the endoplasmic reticulum.

Insulin controls adipocyte metabolism through changes in protein localisation. Here, the authors use cell-wide subcellular proteomics to uncover extensive insulin-regulated protein redistribution and identify C3ORF18 as a regulator of adipocyte insulin sensitivity.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

A bioelectronic device incorporating triphylite (LiFePO₄) as electrode is used for lithium-ion-specific inhibition of peripheral and central nervous system activities in rats and in mice.

Mitochondrial ROS are thought to be involved in NLRP3 inflammasome activation, but how this occurs is unclear. Here, the authors show that cofilin-1 negatively regulates NLRP3 activity by binding it at baseline, but cofilin-1 oxidation by ROS results in dissociation from the complex, thereby releasing NLRP3 activity.

Integrated single-cell and spatial data analysis, combined with bidirectional CRISPR screens, identify the transcription factor GLIS3 as a key driver of chronic inflammation and fibrosis and a potential marker of disease severity in patients with ulcerative colitis.

Emerging multidrug-resistant Neisseria gonorrhoeae is a global health threat in the treatment of gonorrhoea. This study reports the discovery and characterization of a promising antigonorrhoea agent that addresses antibiotic resistance.

Acute perturbation of histone acetylation induces changes in chromatin organization that are only partially reversed once the perturbation is removed and are associated with transcriptional memory effects.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

In a phase 1b trial, patients with treatment-naive metastatic pancreatic adenocarcinoma received the CD73 inhibitor quemliclustat plus gemcitabine and nabpaclitaxel with or without the anti-PD1 antibody zimberelimab, showing encouraging clinical response rates and survival in quemliclustat-treated patients.

Ongoing chikungunya virus replication leads to the accumulation of inflammatory macrophages and CD4⁺ T cells in joint-associated tissues. Inhibition of chikungunya virus replication during chronic disease reduced viral RNA and joint inflammation in mice.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Efficacy of chimeric antigen receptor (CAR)-T in solid tumors are limited by the antigen heterogeneity and tumor microenvironment (TME) induced exhaustion. The authors here manifested that Nr2f6-deficient CAR-T cells have superior anti-tumor effect compared with traditional CAR-T cells, which is associated with enhanced cytotoxic function, followed by durable response due to epitope spreading.

Multi-ancestry GWAS meta-analysis identifies risk loci for severe nausea and vomiting of pregnancy. Downstream analyses explore maternal and fetal contributions of these loci and their temporal effects.

Czernilofsky et al. identified factors that reprogram stromal cells into an inflammatory, dysfunctional state, leading to the structural disorganization of lymph nodes in B cell lymphoma at single-cell and spatial resolutions.

Many genetic loci that are associated with coronary artery disease lack understanding of how they contribute to the disease. Here, the authors combine summary genetic statistics with cell type-specific data of regulatory elements to prioritize candidate disease genes, including non-coding RNA genes.

Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

For individuals with APOL1 high-risk genotypes, which are enriched in individuals of African ancestry, a nine-protein proteomic risk score enables early prediction of kidney disease progression and may, thereby, enable early intervention.