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In two independent studies, Song et al. and Jiang, Dalgarno et al. present computational frameworks, perturbation-response score and Mixscale, respectively, to determine individual cellular variation in response to perturbation.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype with limited effective therapeutic options. Here, the authors identify the RNA-binding protein ELAVL3 as a driver of differentiation into NEPC via a positive feedback loop with MYCN and demonstrate the use of the repurposed drug pyrvinium pamoate to target this axis using preclinical models of NEPC.

Pancreatic cancer detection can be challenging, and is often diagnosed at a late stage. Here, the authors present a cfDNA-based liquid biopsy model that enables early detection and prognosis prediction of pancreatic cancer.

A newly identified coronavirus isolated from farmed minks can use the receptor ACE2 to infect cells of different mammalian species, including human cells, which has implications for potential zoonotic spillover events.

As a potential zoonotic pathogen, porcine deltacoronavirus (PDCoV) has been shown to cause febrile illness in humans. Here, Ji et al. report the structures of PDCoV spike protein bound to porcine and human aminopeptidase receptors, pointing to the likely underlying mechanism of PDCoV zoonotic transmission.

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.

CDK5 is known to drive glioblastoma tumorigenicity but the downstream molecular mechanism is unknown. Here, the authors show that CDK5 activates STAT3 signalling via the nuclear import of TRIM59, which leads to the degradation of the tumour suppressor macroH2A1.

A reproductive barrier between japonica and indica rice subspecies hinders hybrid breeding. Here, the authors reveal that structural and copy number variations of a pollen-essential gene, which encodes a DUF1618-domain protein, result in allelic suppression and subsequently cause hybrid male sterility.

Glioma is a complex disease, and prognosis can depend on clinical, genomic and radiological information. Here, the authors develop a multimodal fusion subtyping model to integrate data modalities for predicting glioma subtypes.

Liang, Yan, Long, Ji et al. find that the origin and dynamics of 5-hydroxymethylcytosine (5hmC) during early development are not conserved between humans and mice and that 5hmC contributes to the activation of human embryonic genes.

The molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.

Determining glioma types directly from whole-slide images (WSIs) would be of great diagnostic utility. Here, the authors develop a deep learning model to identify diffuse glioma types from WSIs according to the 2021 WHO classification across multiple cohorts and with interpretable features.

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.

Depletion of cohesin subunit RAD21 increases DNA breaks genome-wide, leading to translocations at cancer-mutated hotspot genes. RAD21 depletion leads to dormant origin firing and induces irregular replication timing.

Chromosomal structural variations induced by CRISPR/Cas hinder its application in clinics. Here, the authors fuse Cas9 with optimized TREX2 to generate Cas9TX, which can prevent perfect repair and inhibit repeated cleavage.

The cytokine like protein FAM3D (Fam3D in mice) is highly expressed in the digestive tract with unknown role in colon pathophysiology. Here, by using gene deficient mice, the authors show that Fam3D is critically involved in colon homeostasis, host defense against colitis-associated carcinogenesis, and the balance of microbiota.

EGF receptor (EGFR) amplification and mutation are major drivers in glioma tumorigenesis but this mechanism is not well understood. Here, the authors show EGFR-upregulated H3K23ac binds TRIM24 which recruits STAT3, leading to activation of STAT3 signaling, enhancing EGFR-driven tumorigenesis.

Twisted bilayers of 2D semiconductors are being intensively investigated due to their emergent physical properties, but their controlled bottom-up synthesis remains challenging. Here, the authors report a confined-space chemical vapour deposition strategy to synthesize MoS₂ bilayers with twist angles ranging from 0° to 120°.

Zhang et al. show that the regulation of PDHE1α subcellular localization by a phosphorylation switch coordinates responses to antitumour immune surveillance.

Electroreduction of CO₂ to fuels and chemicals is promising but hindered by its low energy efficiency. Here, the authors develop Cu/Ga bimetallic catalysts with reduced activation energies to mitigate the high concentration overpotential, thereby achieving high energy efficiency for CO₂ reduction.

Interferon-gamma (IFN-γ) is an important but not exclusive proinflammatory mediator in macrophages. Here authors show that IFN-γ-independent macrophage autoactivation involves endoplasmic reticulum (ER) stress which in turn induces the GTP-binding protein Septin2 to limit inflammation via a negative feedback loop.

Degradable polymeric porous microcapsules loaded with exosomes from mesenchymal stem cells or regulatory T cells led to the restoration of retinal thickness in mice with retinal ischaemia-reperfusion injury and to reductions in inflammatory cells in monkeys with mycobacterial uveitis.

LRR-RLKs are also widespread in plants and oomycete pathogens. Here, the authors report that an LRR-RLK from Phytophthora sojae can activate pattern-triggered immunity in host soybean and nonhost tomato and Nicotiana benthamiana plants.

To run algorithms on a computer they are broken down into logical operations that are implemented in hardware. A quantum logical AND gate has now been demonstrated, which could substantially improve the efficiency of near-term quantum computers.

Nanoparticles with different chiralities have different in vitro and in vivo effects on the immune system, suggesting new ways of creating vaccine adjuvants.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The oncogenic activity of Hexokinase 2, the first rate-limiting enzyme of glycolysis, requires its mitochondrial localization. Here, the authors show that SUMOylation of hexokinase 2 disrupts its binding to mitochondria and protects cells from tumorigenesis in prostate cancer.

How glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) interact to promote progression of glioblastoma multiforme (GBM) is currently unclear. Here, the authors demonstrate a role for the ARS2/MAGL signalling in regulating self-renewal and tumorigenicity of GSCs and M2-like TAM polarization.

Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are members of the complex II superfamily. Here, the authors present the 2.8 Å cryo-EM structure of Mycobacterium smegmatis Sdh2, which reveals membrane-anchored SdhF as a component of the complex and they discuss the electron/proton transfer pathway in the Sdh2 trimer.

Liu and colleagues show that a previously described G396R variant of the human IGHG1 gene offers increased protection from SARS-CoV-2 and bacterial infections.

Methods that perform data integration are needed to analyse spatial transcriptomics data from multiple tissue slides. Here, the authors present PRECAST, an efficient data integration method for multiple spatial transcriptomics datasets with complex batch or biological effects between slides.

Protein phosphatase Cdc25 controls cell cycle transitions by dephosphorylating CDK substrates. Here, the authors show that the Cdc25A isoform regulates glycolysis through dephosphorylation of pyruvate kinase PKM2, resulting in β-catenin activation and consequent upregulation of the transcription of glycolytic genes.

Chemodynamic therapy relies on Fenton or Fenton-like reactions to produce hydroxyl radical in the tumor region. Here the authors design a two-dimensional interplanar heterojunction with in situ hydroxyl radical generation under ultrasound irradiation, showing anti-cancer activity in preclinical models.

The establishment of a pre-metastatic niche is a key step preceding metastasis formation. Here the authors show that tumor-intrinsic Lin28B, a RNA-binding protein, has an essential role in the formation of an immune-suppressive pre-metastatic niche, promoting lung metastasis of breast cancer.

Echovirus 30 (E30) belongs to the Enterovirus-B group and causes aseptic meningitis in humans. Here, the authors present the cryo-EM structures of the E30 E-particle, A-particle and the mature virion, as well as structures of E30 in complex with its receptor FcRn and CD55, and furthermore they describe a structure-based algorithm that allows the prediction of EV receptor usage.

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.

Obesity is often accompanied by chronic inflammation. Li and colleagues show that, in mice fed high-fat diets, IL-1 signaling in adipocytes induces an unconventional IRAK2 translocation to mitochondria and suppresses respiratory super-complex formation to alter mitochondrial function, and exacerbates obesity.

6-phosphogluconate dehydrogenase is commonly upregulated in cancers. Here, the authors show that activation of EGFR induces phosphorylation of this enzyme at Y481 to activate the pentose phosphate pathway, which consequently reduces ROS and accelerates DNA synthesis to promote tumor growth and radioresistance.

AF6, an essential protein for the organization of cell-to-cell junctions and development, is aberrantly expressed in several tumors but its role in pancreatic cancer is not clear. Here the authors show that in pancreatic cancer, loss of AF6 expression leads to induction of the EMT transcription factor Snail.