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EGFR amplification can affect temozolomide sensitivity in glioblastomas (GBM). Here the authors show that EGFR signalling mediates lysine methylation of NFAT5 which contributes to reduced efficacy of temozolomide in GBM.

A cluster-randomized trial carried out across 980 villages in a high-risk region in China found that systematic treatment of antibiotics, omeprazole and bismuth modestly reduced gastric cancer incidence in Helicobacter pylori-positive populations.

NDRG2 upregulation triggers astrocytic apoptosis in depression by inhibiting AKT and activating the FoxO3a-Puma pathway. Targeting NDRG2 rescues astrocyte loss and alleviates depressive-like behaviors.

The activity of PD-1 blockade in patients with sarcoma has been modest so far. Here, the authors report the results of a pilot clinical trial to assess the efficacy and safety of bempegaldesleukin, a CD122-preferential interleukin-2 (IL-2) pathway agonist, in combination with the PD1 blockade (nivolumab) in patients with locally advanced or metastatic high-grade sarcoma.

Functional succinate dehydrogenase (SDH) complex is vital to mitochondrial homeostasis. Here the authors show that disruption of SDH assembly in the heart causes dilated cardiomyopathy via impairing the mitochondrial integrity and metabolism and that mitochondrial interventions can be an effective approach to ameliorate the disease progression.

Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.

Class IIa histone deacetylases (HDACs) are generally viewed as noncatalytic readers of acetylated lysines within proteins. Specific inhibitors of class IIa HDACs, based on a new zinc-binding scaffold, offer chemical probes to explore the biological function and potential druggability of this enzyme subclass.

Two side-by-side papers report that H3K27me3 deposited by polycomb repressive complex 2 represents an epigenetic barrier that restricts naive human pluripotent cell differentiation into alternative lineages including trophoblasts.

Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1^+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

Here, Wang and colleagues combine short and long sequencing reads to characterize structural variations, prophage and CRISPR spacer elements in human gut microbiomes, and reveal functional differences at a finer level of bacterial strains.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Transposable elements, also known as junk DNA, constitute nearly half of the human genome. This Review by Liang et al. discusses how tumours exploit these transposable elements during their evolution but also how they represent a vulnerability that could be targeted through immunotherapeutic approaches.

Through CRISPR–Cas9 and kinase inhibitor screening, Zhang et al. show that PKCβII phosphorylates and activates ACSL4 to enhance polyunsaturated fatty acid-containing lipid biosynthesis, thereby promoting accumulation of lipid peroxidation and ferroptosis.

The rise of large language model (LLM) technology offers new opportunities for advancing chemical synthesis. Here, the authors developed an LLM-based reaction development framework (LLM-RDF) to copilot the design and experimental tasks throughout the end-to-end chemical synthesis development.

Poorly differentiated hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis. Here the authors show that GDF1, a member of the TGF-β superfamily, is highly expressed in high-grade poorly differentiated HCC and is associated with tumor plasticity, and that GDF1-induced reexpression of cancer testis antigens could render tumors sensitive to immune checkpoint inhibition.

Antiferromagnetic phase transition is observed in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites.

Unsorted retired batteries pose recycling challenges due to diverse cathodes. Here, the authors propose a privacy-preserving machine learning system that enables accurate sorting with minimal data, important for a sustainable battery recycling industry.

Gut microbiota play pivotal roles in IBD. Here, Ning et al. use a multi-omics approach to characterize gut microbiota and metabolites alterations, and potential pathogenic bacteria associated with IBD, with the aim to help develop more precise biomarkers for IBD diagnosis and drug targets

ASPP1 promotes apoptosis of cardiomyocytes by increasing the trafficking of p53 to the nucleus. Here the authors show that, in fibroblasts, ASPP1 promotes the ubiquitination and degradation of p53, decreasing myofibroblast activity and improving cardiac fibrosis and function after myocardial infarction.

The dual-specificity kinase DYRK3 acts as a central ‘dissolvase’, mediating the phase transitions of several types of membraneless organelles during mitosis.

Wang, Zhang, Zheng et al. demonstrate that tumour cell-derived lymphotoxin-β activates NF-κB2 signalling and CCL2/5 secretion in osteoblasts to promote bone metastasis in breast cancer, which may potentially be targeted with a decoy receptor in vivo.

Genome-wide comparative analysis of DNA binding for 200 transcription factors in two maize inbred lines reveals prevalent genotype-specific variation that is associated with gene expression differences and agronomic traits.

Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder with high morbidity and mortality, and there is no specific drug to treat it. Here, the authors show that the AR-CAND1-ACAA2 axis regulates the development of NAFLD, and enhancing the function of CAND1 is a promising strategy for the development of a therapeutic agent for NAFLD.

Envelope glycoproteins from Asia prevalent HIV-1 subtypes, CRF01_AE and CRF07_BC, remain less explored. Here, the authors reveal the unique features of their V1 regions, associate them with the resistance to certain broad neutralising antibodies (bNAbs), and unravel the epitope and mechanism of a bNAb from CRF01_AE infected individuals.

Exercise has positive effects on the brain during aging. Here the authors show that in mice, platelet-released exerkine PF4 mediates the effects of exercise on the brain.

Precise regulation of the phytohormone gibberellin to optimal levels may not only confer alkali–thermal tolerance to Green Revolution rice varieties but may also further enhance their yield, and ATT2, by enabling the fine-tuning of gibberellins, is expected to be a potential new post-Green Revolution gene.

The hardness and incompressibility of diamond makes it an ideal material for high-pressure anvil cells. Here, a method for generating static pressure is described in which graphene-coated diamond is heated, forming graphene nanobubbles that trap water at pressures sufficient to etch the surface of diamond.

Several GWAS have identified many common variants associated with blood metabolites. Here, the authors use an exome array to identify low frequency, potentially functional variants that impact human metabolism.

Hashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. Here the authors develop a deep learning model for diagnosis of HT on a large multi-site dataset including image and video data.

In the absence of transcription, gene expression required for oocyte maturation is regulated by translation of preexisting mRNAs. Here the authors show that a defective program of mRNA translation in oocyte is associated with maternal aging.

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.

Here, the authors demonstrate that CXCL5 expression is increased in ankle joints of gouty arthritis model mice. CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and joint inflammation.

The unclear understanding of the interphase has limited advancements in battery performance. To address this, the authors designed sulfoximide salts with distinctive interphasial chemistry, enabling high-performance lithium metal batteries even under extreme conditions.

LCRMP-1 serves as a transcriptional co-regulator that enhances the transcription of SERPINE1, thereby facilitating angiogenesis in lung adenocarcinoma.

Inhibition of intestinal MYC is shown to have beneficial metabolic effects by promoting GLP-1 secretion and reducing ceramide production.

KRAS^G12D mutations frequently co-occur with mutated TP53 tumour suppressor in patients with pancreatic ductal adenocarcinoma (PDAC). Here the authors report the design of dual targeted therapeutic extracellular vesicles containing high copy numbers of TP53 mRNA and siKRAS^G12D, showing anti-tumor activity in PDAC preclinical models.

An orally delivered encapsulated bacterial cocktail that metabolizes blood nitrogenous waste products in the gut reduces urea and creatinine concentrations in the blood of animal models of acute and chronic kidney injury.

Cyclases that are able to build medium-sized rings are rare and mechanistic insights are sparse. Now, computational and experimental studies reveal how SoBcmB enables the construction of an eight-membered O-heterocycle over the intrinsically more favourable five-membered tetrahydrofuran in bicyclomycin biosynthesis.