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The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Chen et al. report that the immune modulatory metabolite itaconic acid selectively inhibits the activity of TET DNA dioxygenases to repress the inflammatory responses.

HPV’s E6 protein promotes cancer by degrading p53. This study reveals the cryoEM structure of HPV16 E6 in complex with E6AP and p53, highlighting their picomolar affinity and large protein-protein interaction interface.

Tang, Zhang, Fang, Zhu et al. identify impaired mitochondrial fusion and biogenesis as a key mechanism underlying NOTCH1-associated aortic pathology and show that correcting mitochondrial loss in mutant mice using repurposed drugs teriflunomide or leflunomide slows the progression of aoropathy.

Zhang et al. demonstrate that the smooth muscle-specific deficiency of the mitochondrial NAD⁺ transporter SLC25A51 impairs the biosynthesis of proline and type III collagen and results in thoracic and abdominal aortic aneurysm.

Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.

Liu et al. show that the non-oxidative pentose phosphate pathway is crucial for maintaining regulatory T cell (T_reg) function, as deletion of transketolase in T_reg cells results in loss of immune tolerance in mice.

The authors here present a detailed reconstruction of the landslide mass following the 2018 eruption of Anak Krakatau. Bathymetry data reports the volume of the collapsed submarine flank to be much larger than previously reported.

NCOMMS−24−25010C Penetrating orocutaneous or oropharyngeal fistulas (POFs) are hard to treat, due to tissue deficiency, saliva contamination, and dynamic oral conditions. Here, the authors report a Janus hydrogel adhesive that prompts POF wound healing by seamless plugging of the penetrating wound, protecting it from mechanical stimuli and bacterial infection, and creating a pro-healing microenvironment.

It is seemingly in the interest of high-income countries to prioritize vaccinating their own population against COVID-19, despite it being immoral. However, mathematical modelling by Ye et al.¹ shows that this approach offers only limited, short-term benefits, whereas equitable vaccine distribution would substantially curb the emergence and spread of new variants.

Delivering gene editing materials to the brain for glioblastoma therapy can boost the efficacy of chemotherapy. Here the authors reduce resistance to temozolomide using a reactive oxygen species-sensitive polymer-locking fusogenic liposome that can cross the blood–brain barrier and deliver short interfering RNA or CRISPR–Cas to glioblastoma with high specificity.

The performance and stability of flexible perovskite solar cells are limited by the fragile grain boundaries in perovskite films. Here, authors achieve in-situ bifacial capping to flatten the grain boundary grooves and demonstrate stable flexible inverted devices with maximum efficiency of 23.7%.

How sulfur dioxide emitted through coal combustion is oxidized to sulfate particles during winter haze pollution events has been the subject of debate. Here, the authors show that rapid oxidation takes place by nitrogen dioxide and nitrous acid, producing nitrous oxide together with sulfate.

Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.

One of the main problems of membranes used in wastewater managements is that they are easily affected by fouling. A thin-film composite nanoporous membrane obtained by co-deposition of dopamine and polyethyleneimine shows effective electrodialytic fractionation of organics and NaCl with almost zero membrane fouling.

A community-led randomized controlled trial in China showed that a pay-it-forward incentives increased the uptake of hepatitis B and C virus testing in men who have sex with men as compared with standard-of-care.

In a magneto-electric material, the magnetic and electric properties are coupled. This coupling allows the magnetic order to be controlled by electric stimuli, making magnetoelectric materials promising candidates for new data storage technologies. Here Gu et al demonstrate a magnetoelectric effect in a van der Waals antiferromagnetic CrOCl which persists down to monolayer, and using this realize a multi-state data storage device.

The knowledge in the large language model (LLM), generative pre-trained transformer (GPT) 3.5, is elicited to facilitate the discovery of MRE11 in regulating sleep in the presence of conspecifics by a multi-object video tracking system.

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.

The Chinese tree shrew, Tupaia belangeri chinensis, has been proposed as a potential animal model in biomedical research and drug safety testing. This study presents the full genome of the Chinese tree shrew, identifying common features between the tree shrew and primates.

Factors affecting the fate of disseminating tumour cells in the circulation play a critical role in metastasis. Here the authors show that TLR4 on platelets promotes their adhesion to tumour cells and enhances metastasis.

Dysregulation of basal progenitor cells induces esophageal tumorigenesis but the underlying mechanism is less explored. Here, the authors show that Jag1/2 deficiency promotes expansion of basal progenitor cells, leading to reduced squamous epithelial differentiation and enhanced formation of squamous cell carcinoma in the foregut.

Epitaxial growth of heterostructures composed of materials with large lattice mismatch is challenging. Here, the authors reported the epitaxy of II-VI semiconductor nanorods on plasmonic noble metal, despite a lattice mismatch of more than 40%.

Correct diagnosis of primary central nervous system lymphoma is key in determining treatment, however, this depends on pathology analysis. Here, the authors develop a deep learning method to diagnose primary nervous system lymphoma from stained whole-slide images.

Plutella xylostella endures Bt toxins with no performance costs. This study reveals how, depending on the presence of the toxin, this insect modifies MAPK phosphorylation to modulate the transcription factor FTZ-F1 binding, to up- or down- regulate Bt receptors or non-receptor (resistant) paralogs.

CDK4/6 inhibitors have improved outcomes for patients with ER+ breast cancer, however, those with loss of RB1 function often fail to respond. Here, the authors identify a vulnerability of ER + /RB1- breast cancer on PRMT5 and via dual blockade of ER and PRMT5 therapeutically target this in patient-derived xenograft models.

It has been proposed that, during development, clonally related neurons migrate along the same radial glial fibre to form clusters of functionally similar cells; here, sister neurons in the same radial clone are shown to have similar orientation preferences in mice, providing support for this hypothesis.

Misfolded SOD1 has been linked to both familial and sporadic ALS. Here the authors have determined the cryo-EM structure of SOD1 fibrils, providing insights into the conversion of SOD1 from its immature form into an aggregated form during pathogenesis of ALS.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Zhu et al. found that cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. Phospholipid synthesis acts as an integrative defense mechanism to sense and combat oxidative stress.

The hearing-loss phenotype can be corrected via the injection, into the inner ear, of a base editor packaged in an adeno-associated virus, as shown in mice harbouring a mutation homozygous to human OTOF and in humanized mice with the human mutation.

The precise control of interlayer stacking mode of 2D materials is a long-standing pursuit. Here, the authors report two 2D copper-organic frameworks that can undergo the reversible interlayer sliding through environmental stimulation.

Several micro RNAs have been shown to be deregulated in brain tissue or sera from individuals with Alzheimer’s disease and in AD mouse models. The authors show that miR-135a-5p is downregulated in excitatory pyramidal neurons from AD mice and that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in AD.

Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.

Cigarette smoke induces microRNA dysregulation in cancers. Here, the authors show that cigarette smoke promotes the maturation of oncogenic primary miR-25 due to METTL3 hypomethylation, and mature miR-25 suppresses PH domain leucine-rich repeat protein phosphatase 2, resulting in oncogenic AKT activation in pancreatic cancer.

Accurate monitoring of chronic kidney disease (CKD) progression is essential for efficient disease management. Here Chen et al. identify five serum metabolites in patients with stage 1–5 CKD whose levels associate with disease progression, and find that 5-methoxytryptophan and its regulatory enzyme TPH-1 exert anti-fibrotic effects in mouse models of kidney injury.

A recombinant vaccine that targets the receptor-binding domain of the spike protein of SARS-CoV-2 induces a potent antibody response in immunized mice, rabbits and non-human primates, and protects primates from infection with the virus.

An analysis of the immunoglobulin repertoire of B cells in Peyer’s patch germinal centres in mice provides evidence for the selection of B cell receptor clonotypes by gut antigens and antigen-driven affinity maturation.

The functional-metabolic state of macrophages fundamentally influences the tumour microenvironment, making adoptive cell therapy with pro-inflammatory macrophages an attractive anti-tumour approach. Here authors introduce pluripotent stem cell-derived CAR-macrophage that are depleted of ACOD1, an essential gene in itaconate metabolism, which reprograms them to a pro-inflammatory state enabling enhanced anti-tumour function.

Intestinal aging is associated with declines in structure and absorption of nutrients. Here, the authors show that aging related intestinal decline is mediated by activation of the mTORC1-p38MAPK-p53 pathway in intestinal stem cells and can be ameliorated by abrogating mTORC1 or p38MAPK activity.

The discovery of biomarkers remains challenging owing to a lack of methods sensitive enough to identify such rare molecules. Now, by simultaneously exploiting the catalysis and affinity of a DNAzyme, candidate biomarkers with low abundance in cancers can be pulled down for identification and validation.

Using a physical trade flow approach and structural decomposition analysis, this study estimates consumption-based greenhouse gas emissions throughout food supply chains over 2000–2019, revealing overall trends and five underlying drivers.