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In 1923, Otto Warburg published his landmark study, in which he described his seminal observations related to metabolic shifts in cancer, often referred to as the Warburg effect. His work laid the foundation for an understanding of how metabolic reconfiguration contributes to cancer onset and progression. Several researchers in the field share their thoughts on what this discovery means to them and how it has inspired their scientific journey.

Interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II (CAMK2) phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), enabling glutathione peroxidase 4 (GPX4) interaction, promoting α-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation and stabilizing GPX4 to counteract ferroptosis.

Many thrombolytic agents depend on plasminogen, leading to D-dimer accumulation. Here, Tang et al. report a plasminogen-independent thrombolytic enzyme that degrades blood clots and D-dimer without plasminogen.

Ming, Yang, Huang et al. design a chimeric matchmaker peptide, which targets a senescent cell-specific surface marker and modifies the cell surface with polyglutamic acid. This promotes interactions with natural killer cells and senescent cell clearance in liver fibrosis, lung injury, cancer and natural aging.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.

Duan, Hu, Han, Lei, Wang et al. report that ADSL-mediated production of fumarate suppresses STING activation and impairs T cell and NK cell infiltration, thereby facilitating immune evasion in breast cancer.

Protein kinase R-like endoplasmic reticulum kinase-phosphorylated adenylosuccinate lyase (ADSL) binds to Beclin1 upon lipid deprivation. ADSL-produced fumarate increases Beclin1 K117 dimethylation by inhibiting lysine demethylase 8 activity, resulting in disrupted binding of BCL-2 to Beclin1, enhanced autophagy and liver tumor growth.

Tao et al. show that epidermal growth factor receptor and insulin-like growth factor 1 receptor activation enhances thymidine kinase 1 expression through ERK phosphorylation and deubiquitylation mediated by ubiquitin carboxyl-terminal hydrolase 9X, thus enhancing enzyme activity-dependent DNA synthesis and enzyme activity-independent glycolysis.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

The synthesis of covalent organic frameworks (COFs) by a soft-template methodology is challenging. Here, the authors attach the soft templates to the COFs backbone via ion bonds, avoiding crystallization incompatibilities and allowing subsequent removal of the template by ion exchange for enhanced U(VI)/Th(IV) adsorption performance.

The histone acetyl transferase KAT2A (also known as GCN5) can also catalyse histone succinylation, with the α-KGDH complex providing a local source of succinyl-CoA.

The preferential oxidation of CO (PROX) in hydrogen is a promising solution for hydrogen purification. Here the authors report a novel bimetallic Pt-Fe catalyst with ultralow metal loading which delivers excellent catalytic activity and selectivity in PROX, while maintains good stability for a long period.

Symbiotic nitrogen fixation (SNF) in legumes is suppressed by the presence of soil inorganic. nitrogen (N). Here the authors characterize a transcriptional regulatory network underlying the N-inhibition of SNF in soybean nodules.

The clinical outcomes of esophageal squamous cell carcinoma (ESCC) remain poor, and thus it remains critical to find prognostic molecular markers. Here, the authors identify prognostic ESCC subtypes based on bulk and single-cell RNA-seq combined with histology AI in samples from patients with more than four years of follow-up, and find markers associated with immune evasion.

The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G₀–G₁ phase, thus suppressing proliferation in human hepatocellular carcinoma cells.

Wang et al. provide insight into how acetate promotes tumour growth by reprogramming lung cancer metabolism and promoting immune evasion.

Upon nutrient stress in hepatocellular carcinoma, the glycolytic enzyme PFKL facilitates mitochondria tethering to lipid droplets to engage lipid mobilization and ensure nutrient supply.

Interorgan communications play key roles in the regulation of whole-body energy metabolism. Here, the authors report the myokine Musclin as a negative regulator of beige adipose thermogenesis and systemic energy homeostasis through Tfr1/PKA signalling mediated muscle fat crosstalk.

Bin Han and colleagues report the draft genome of moso bamboo, an important non-timber forest product. RNA sequencing analysis of bamboo flowering tissues suggests a connection between drought-responsive genes and potential flowering genes.

The efficiency of reprogramming of fibroblasts into induced dopaminergic neurons is often low. Here, Jiang et al.demonstrate increased transdifferentiation rates by inducing cell cycle arrest, suppressing p53, Tet 1 and by adding neurotrophic factors to the media.

Using structural and functional analysis, Li et al. reveal the architecture of the Rpd3S histone deacetylase complex and mechanism of its chromatin targeting and deacetylation.

Accuracy loss and slow speed affect the identification of compounds through matching of mass spectra using a large-scale spectral library. Here the authors use Word2vec spectral embedding and hierarchical navigable small-world graph to improve accuracy and speed of spectral matching on their own million-scale in-silico library.

With the example of the paraspeckle protein PSPC1, Shao et al. demonstrated the synergistic interplay of promoter-associated RNA and its binding proteins in promoting transcription condensate formation and Pol II engagement and activity via phase separation.

The metabolism of temozolomide (TMZ) to form methyldiazonium ions and 5-aminoimidazole-4-carboxamide (AICA) results in DNA damage, despite this, resistance frequently occurs in glioblastoma. Here, the authors demonstrate that AICA is further metabolised by HPRT1 into AICAR, which activates AMPK signalling and increases DNA damage repair. Targeting this axis in preclinical glioblastoma models sensitised tumours to TMZ.

Cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in Chinese Han and white British participants identify autosomal and X-chromosomal associations in more diverse populations.

Lu and colleagues delineate a pathway through which the PKM2 enzyme promotes aerobic glycolysis, known as the Warburg effect, in cancer cells. They show that EGFR-activated ERK phosphorylates PKM2, leading to its accumulation in the nucleus. Nuclear PKM2 subsequently promotes the c-Myc-dependent upregulation of genes involved in the Warburg effect, resulting in tumour growth.

TERT was dephosphorylated by the protein phosphatase activity of the gluconeogenic enzyme FBP1, leading to inhibition of TERT nuclear translocation and telomere function. Lipid nanoparticle-delivered FBP1 mRNA blunts tumor growth in mice.

It is needed yet difficult to achieve a strategy for synthesizing single-atom nanozymes that integrate atomic metal dispersion, elevated mass transport and tailorable coordination environment. Here, the authors address this issue by developing a biomimetic synthetic strategy and demonstrate the application of the resultant single-atom Fe nanozymes for tumor visual identification.

Shao et al. show that EGFR signaling increases expression of the complement regulatory proteins CD55 and CD59, suppressing the complement. This is mediated via a sponging lncRNA and interfering with the axis synergizes with immunotherapy.

Chemo-resistance and immune evasion are major challenges in osteosarcoma treatment. Here the authors show that doxorubicin promotes IL-18 secretion by tumor associated macrophages inducing LAT2-dependent CD47 upregulation in osteosarcoma cells, suggesting LAT2 inhibition as a therapeutic option in combination with doxorubicin.

Glucose metabolic enzymes and their metabolites provide cells with energy and building blocks for the synthesis of macromolecules. However, it has become clear that they also have non-canonical functions, which modulate various cellular activities. In this Review, Guo et al. discuss how these moonlighting functions can help drive cancer progression.

Zhao et al. report a role for glutamine synthetase in regulating cell proliferation that does not require the catalytic activity of the enzyme.

Single-crystal graphene can be grown on a copper foil at a rate of 60 μm s^-1 by using an adjacent oxide substrate that continuously supplies oxygen to the surface of the copper catalyst.

The epitranscriptomic regulation of adenomatous polyposis coli (APC) tumour suppressor gene in cancers is unclear. Here the authors show that N6-methyladenosine methylation writer METTL3 downregulates APC by recruiting YTHDF2 for APC mRNA degradation, and that this promotes glycolysis and tumour growth in oesophageal cancers.

A balance between high stability and rapid degradation is required for effective photothermal anti-cancer agents. Here, the authors use Cu²⁺ to accelerate the degradation of black phosphorus nanosheets while enhancing its photothermal ability and apply this material for PET-guided, CDT-enhanced combination cancer therapy in mice.

Lu and colleagues find that in response to ionizing radiation, DNA-PK phosphorylates fumarase breaks for local generation of fumarate, which in turn enhances DNA-PK recruitment by inhibiting histone H3 demethylation.