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DNA damage from chemotherapy can activate cGAS–STING and interferon pathways. Here, the authors show that cGAS–STING signaling is specific to DNA rich in CA repeats, whereas DNA not rich in CA repeats is detected by AIM2, resulting in opposing tumor immune responses.

Oxaloacetate is sensed by MDH1, which primes innate immune antiviral defence against influenza virus infection, thus resulting in the activation of ETS2 to promote TBK1-centred type I interferon signalling.

Two phase 2 trials, along with translational analysis of prospective cohorts and experimental analysis, indicate that immunosenescence as a mechanism of resistance to immunotherapy can be overcome with the senolytics dasatinib and quercetin in patients with head and neck squamous cell carcinoma.

Zhang et al. show that Egr1 regulates transient senescence during neonatal heart regeneration and upon agrin-mediated cardiac repair in adult mice, acting downstream of the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts.

The authors use a machine learning approach and in situ pigment samples to identify summer shifts (1997–2023) in the abundance and composition of Antarctic phytoplankton. While smaller phytoplankton groups generally increased, diatom chlorophyll a broadly decreased, with putative impacts on food webs and the carbon sink.

Li and colleagues report that a septo-enteric polysynaptic circuit that is activated by chronic stress links the brain to the tumor microenvironment to promote colorectal cancer growth.

Auranofin is an FDA approved antirheumatic gold drug with antitumoral properties but reduced by serum. Here, the authors discover that supplementation of clinically relevant thiol ligands allows gold to retain active small-molecule structures while enhancing its antitumoral activity at approved dosage.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Inspired by class II aldolases found in nature, the authors report a biomimetic copper/squaramide cooperative catalysis strategy for asymmetric Mannich reactions between challenging acyclic ketimines and α-substituted β-keto esters.

Timely identification and treatment of cerebral lesions in high-risk neonates are crucial. Here, the authors present a deep learning system that extracts multiple standard views from neonatal cranial ultrasound videos and diagnoses severe cerebral lesions with high accuracy, outperforming junior radiologists.

The diagnosis and prognosis of chronic kidney disease (CKD) relies on invasive renal biopsies, which can be clinically constrained. Here, the authors develop a non-invasive model using retinal images that can be used to screen for CKD and identify five common pathological types of CKD.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Senescent cells accumulate during aging and exhibit cell enlargement, the function of which has been unclear for decades. Here, the authors identify an antagonistic genetic circuit for hypertrophy and reveal its instructive role in modulating the SASP.

The authors show that, in addition to rising daily mean near-surface air temperature, the faster increase in daily maximum temperature compared to minimum temperature has contributed to increasing near-surface air dryness since the 1980s.

Zhang et al. delineate the heterogeneity of core regulatory circuitry in glioblastoma and identify HOXB3 condensation as a vulnerability that may be targeted with a therapeutic peptide in mouse models.

The mechanism underlying abnormal pain perception in autism remains unclear. Here authors show that histone lactylation decreases Dock4, an autism-related gene, to modulate heat pain by impairing Dynein-mediated Nav1.7 membrane trafficking, providing insights into thermosensor-independent mechanisms.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Mesenchymal stromal cells (MSCs) demonstrate therapeutic benefits in multiple diseases, but the mechanisms remain unclear as infused MSCs do not persist in the body. Here, the authors show that MSC apoptosis is an important mechanistic element, as MSCs rendered genetically incapable of apoptosis lose their ability to ameliorate disease.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

Direct human actions such as hunting and bird deterrence at aquaculture sites kill up to 10% of the populations of some shorebird species migrating along China’s coast each year, suggesting that this direct mortality is an overlooked threat to migratory populations.

R9AP is a key receptor for entry of Epstein–Barr virus into human epithelial and B cells, and interacts directly with the viral glycoprotein gH/gL complex to mediate virus–host membrane fusion.

The authors use long-term ground and satellite data to reveal the impact of drought on autumn date of foliar senescence (DFS). They link increased drought impacts to precipitation changes and plant functional traits and project earlier DFS by the end of the century, particularly at high latitudes.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.

The principal layer architecture of the sensory cortex is altered with aging. The authors show that overall thinning of the primary somatosensory cortex is driven by deep layer degeneration but that layer IV is more pronounced in old age.

Desmocollin 2 (DSC2) binds to the EBV glycoprotein H/glycoprotein L complex and allows for virus entry to epithelial cells, which could be blocked by DSC2-specific antibodies. DSC2 allowed for virus entry independent of Ephrin receptor A2.

Current prognostic biomarkers for colorectal cancer (CRC) tend to lack generalisability across different cohorts and platforms. Here, the authors introduce PIANOS, a classifier for stratifying CRC patients into distinct risk groups across different platforms and cohorts, which allows predicting clinical outcomes and therapies.

Nie et al. show that myocardial CCDC25 detects doxorubicin-induced neutrophil extracellular trap DNA and activates reactive oxygen species production and autophagy, leading to cardiotoxicity. Targeting CCDC25 exerts a cardioprotective effect without impacting the antitumor activity of doxorubicin in lymphoma and breast cancer models.

Aging leads to progressive loss of effective tissue regeneration, which has been linked to the accumulation of senescent cells. Here, the authors use machine learning to identify a stable nuclear morphometric phenotype that detects senescent cells across tissues and age, enabling their quantification and mapping in diverse environments.

Going from model development to a pilot implementation study, a deep learning model shows that acute aortic syndrome can be diagnosed directly from noncontrast CT, increasing accuracy and decreasing time to diagnosis.

The recalcitrance of many infections to antibiotic treatment may be due to the presence of ‘persisters’, or non-growing, antibiotic-tolerant bacteria. Here, the authors study the structures and functions of aminoacyl-tRNA acetyltransferase toxins, and their roles in persister formation in Salmonella.

The analysis of radial velocity variations of O-type stars in the Small Magellanic Cloud reveals a large fraction of close binaries, suggesting that binary physics also plays a prominent role in the low-metallicity environment of the distant Universe.

Mitochondrial fatty acid β-oxidation is essential for cellular energy production. Here the authors show that mutations in Testis-Expressed Protein 44 (TEX44) are associated with misregulated fatty acid β-oxidation and male infertility.

Multi-omic analysis of 39 samples of treatment-naive and recurrent nasopharyngeal carcinomas highlights the importance of the tumor microenvironment in promoting radioresistance and immune escape.

Chini et al. demonstrate that CD38⁺ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38⁺ affects intracellular NAD⁺ levels in vivo by hydrolyzing the NAD⁺ intermediate nicotinamide mononucleotide extracellularly.

Neoadjuvant cancer therapeutic strategy has been explored in phase I/II clinical studies for head and neck squamous cell carcinoma. Here this group reports a single-arm, phase II clinical trial evaluating the neoadjuvant radiotherapy plus PD-1 inhibitor tislelizumab combined with paclitaxel and cisplatin, followed by radical surgical resection on 28 patients with untreated stage III-IVB head and neck squamous cell carcinoma.

During senescence, minority mitochondrial outer membrane permeabilization leads to the release of mtDNA into the cytosol through BAX and BAK macropores, in turn activating the cGAS–STING pathway, a major regulator of the senescence-associated secretory phenotype.