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Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

PARP inhibitors are effective in cancer patients with BRCA1 mutations but whether this can extend to BRCA1 wildtype patients by targeting BRCA1 transcriptional regulation is unclear. Here, in preclinical models of pancreatic cancer, the authors identify OFD1 as a transcriptional regulator of BRCA1 via the DREAM complex and as a potential therapeutic target in combination with PARP inhibition.

Brainstem gliomas are an aggressive form of paediatric cancer. Here, the authors use metabolomics to assess differences in metabolites during radiotherapy.

Nasal colonization by Staphylococcus aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

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.

Here Zhu et al. investigate the ontogeny of type 2 dendritic cells (DC2s) in mice. Using Klf4 expression to distinguish conventional DC precursors from plasmacytoid DCs, they identify two pre-DC2 populations with their development controlled by TCF4 and KLF4 that give rise to DC2A and DC2B cells.

Developing high-current-density catalysts is key to efficient water splitting. Here, the authors report a single-atom Ru-doped amorphous Ni–Mo oxide that dynamically self-reconstructs to retain high activity at industrial current densities in an anion-exchange membrane water electrolyzer.

Substituted 1,3,4-thiadiazoles find extensive use in pharmaceutical, agricultural, and materials chemistry. Herein, the authors report the synthesis of multi-functionalized 1,3,4- thiadiazoles via sulfur-mediated direct coupling between primary nitroalkanes and acyl hydrazines.

The use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

Tao et al. study the role of TRMT6 in colorectal cancer, where it is upregulated and show that TRMT6 supports histone biosynthesis by stabilizing tRNA-Lys-TTT-1-1. Targeting TRMT6 reduced histone mRNA translation in a codon-biased manner.

This study establishes a molecular classification of keloids based on fibroblast differentiation via integrated single-cell/bulk RNA-seq, offering novel insights into pathogenesis and enabling precision clinical management with therapeutic avenues.

Middle-aged obesity, marked by excessive fat accumulation, is closely linked to DNA damage. Here, the authors show that the DNA repair enzyme Eepd1, primarily expressed in adipose tissue, in its myristoylated form, promotes lipolysis and thermogenesis by activating PKA to combat obesity.

Molecular computing is an emerging paradigm with a crucial role in clinical diagnosis. Here, authors develop a spatially localized, DNA-integrated circuits-based classifier, DNA IC-CLA, which enables accurate cancer diagnosis for clinical samples in a faster and more effective manner.

Targeted multielement substitution of a lead-free relaxor ferroelectric perovskite distorts the lattice structure and induces strong polar disorder, leading to high-polar-entropy ferroelectric oxides with a high electrocaloric effect and long lifetime.

Nerve/glial antigen 2 (NG2) glia can sense synaptic inputs from neurons. Here, the authors show NG2 glia form functional GABAergic synapses by regulating inhibitory synaptic transmission onto adjacent hippocampal interneurons, and activation of NG2 glia induces anxiety-like behaviour in a mouse model of chronic social defeat stress.

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy without effective treatments. Here, authors apply prime editing (PE) system to correct the point mutation in a preclinical RP mouse model. In vivo treatment achieves genome editing and restores mice vision.

Treating myocardial reperfusion injury via nanotherapy is challenging due to clearance by the mononuclear phagocyte system. Here, the authors target the spleen to reduce acute heart injury and improve long-term cardiac function via transient IRF7 inhibition.

IleRS knockdown in Mycobacterium abscessus and Mycobacterium marinum disrupts branched-chain and pantothenate metabolism, weakens persistence in host models, and effectively increases pyrazinamide sensitivity.

Low-k nanodiamonds are discovered to possess the ability to concurrently enhance the electrocaloric effect, thermal conductivity, and electrical stability of polymeric nanocomposites, providing support for electrocaloric refrigeration.

Accidental ingestion of Pb-contaminated soils represents a major route of Pb exposure for humans. Here, the authors show an effective and straightforward approach of drinking cola beverages to reduce blood Pb levels following the ingestion of contaminated soils based on animal models data.

Artificial DNA circuits that can perform neural network-like computations have been developed, but scaling up these circuits to recognize a large number of patterns is a challenging task. Xiong, Zhu and colleagues experimentally demonstrate a convolutional neural network algorithm using a synthetic DNA-based regulatory circuit in vitro and develop a freeze–thaw approach to reduce the computation time from hours to minutes, paving the way towards more powerful biomolecular classifiers.

Uterine fluid supports early embryo development. This study reveals maternal high-fat diet alters tsRNA/rsRNA profiles in uterine fluid, leading to abnormal embryonic metabolism and offspring disorders, demonstrating a novel mode of RNA-mediated communication.

Sirtuin 5 (SIRT5) has been associated to colorectal cancer and metabolic regulation. Here, the authors show that SIRT5 silencing reduces nucleotide availability leading to DNA damage and tumor suppression in colorectal cancer models.

Developing anti-gout medications that simultaneously reduce uric acid and exert anti-inflammatory effects is of interest for managing gout progression. Here, the authors employ a dual-target pharmacophore model to design derivatives of β-carboline-1-propionic acid and identify a drug candidate demonstrating potent uric acid-lowering activity in male hyperuricemia mouse models and mitigating NLRP3-mediated inflammation.

Catalytic methods that generate Z-alkenes are rare due to the energetic favourability of the corresponding E-alkenes. Now, a bisphosphine–iron catalyst mediates the multicomponent dialkylation of allenes, using dialkylzinc reagents and alkyl halides, to selectively form functionalized trisubstituted Z-alkenes.

PINK1/Parkin-mediated ubiquitin-dependent mitophagy is a key regulator of browning in inguinal white adipose tissue (iWAT). Here, the authors report that PNPLA7, an Endoplasmic Reticulum and mitochondria-associated membrane (MAM) protein, inhibits browning of iWAT by promoting PINK1/Parkin-mediated mitophagy upon cold challenge or adrenergic receptor agonist treatment.

This paper reports a customizable CRISPR ribonucleoprotein delivery tool, dubbed RIDE, for the treatment of Huntington’s disease in mice, non-human primates and patients’ iPSC neurons.

Vaginal infections influence about 75% of adult women worldwide each year. Here, the authors report a strategy to treat vaginal infection by restoring the homeostasis of the vaginal mucosal barrier through in situ formation of a living-synthetic therapeutic coating.

The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of Ruminococcus bromii mediated biotransformation of the bile acid deoxycholic acid.

This study identifies the compound napabucasin as a promising candidate against refractory Helicobacter pylori infections, demonstrating efficacy compared to standard triple therapy in murine infection models, and probing the mechanism of action.

The adaptable architecture of avian feathers serves as promising inspiration for flapping-wing aircrafts (also known as ornithopters). Here, authors propose a biohybrid mechanoreceptor using natural feathers and piezoelectric materials for precise proprioceptive recognition in flapping-wing systems.

Hyperuniform disordered solids are a unique glass state that exhibits suppressed density fluctuations. Here, authors generate hyperuniform glasses with high stability, identifying key exponents of hyperuniformity tied to jamming, and provide insights into ideal disordered solids and metamaterials.

The potential roles of post-translational modification of bacterial proteins in pathogenesis are not well understood. Here, Wang et al. show that posttranslational lactylation of proteins, in particular alpha-toxin, is important for virulence of the human pathogen Staphylococcus aureus.

T follicular helper (TFH) cell numbers are increased after vaccination and fewer of these cells might result in reduced vaccine responses. Here the authors show in mice and humans that leptin promotes T_FH differentiation and that low leptin levels can impair T_FH response to vaccines and virus protection in mice.

Developing Ru-intermetallic catalysts for mild ammonia synthesis faces structural complexity. Here, machine learning identified Sc_1/8Nd_7/8Ru₂, optimizing Ru–N bonding and orbital hybridization, enhancing catalytic activity under mild conditions.

The diperpenoid adenanthin covalently modifies the resolving cysteine from peroxiredoxins to inhibit the reduction of hydrogen peroxide, a second messenger in cells, and thereby activates pathways that promote the differentiation of leukemia cells.

In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.

Li et al. developed a base-editing system to edit mutations linked to autism. Targeting a mutation in Mef2c restored Mef2c protein levels in several brain regions and reversed behavioral changes in Mef2c-mutant mice.

Lentiviruses co-packaging SpCas9 mRNA and an expression cassette encoding for a guide RNA targeting the Vegfa gene prevent mice from developing wet age-related macular degeneration induced by Vegfa. [Summary amended to correct the description of the packaged cargo.]

A study identifies TMEFF1 as a neuron-specific restriction factor essential for prevention of replication of herpes simplex virus type 1 in the central nervous system.

Acute myeloid leukaemia(AML) modifies the bone marrow(BM) microenvironment, impacting hematopoiesis. Here, the authors demonstrate that AML-modified BM endothelial progenitor cells(EPC) remodelling supports normal hematopoiesis after complete remission and this process is improved by the antioxidant N-acetyl-L-cysteine(NAC).

This study reveals the structural basis of collagen processing by the KOGG complex, revealing how it catalyzes lysine hydroxylation and dual-glycosylation, essential for collagen folding and stability, with implications for collagen-related diseases.

A hybrid cathode interfacial layer (AZnO-F3N) is developed, delivering 21.0% efficiency along with excellent stability, mechanical robustness and broad versatility, highlighting its potential to advance organic solar cells.