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GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

This work introduces roll-to-roll fluidics, a method that enhances reagent efficiency and reduces turnaround time, enabling rapid and economical next-generation sequencing.

Weakly space-confined, large-grained crystals of all-inorganic perovskite were used to fabricate light-emitting diodes with a high external quantum efficiency and operational stability.

It has been previously suggested that STING agonists can improve response to CAR-T therapy. Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models.

Repetto et al. provide an analysis of the genetic basis of variation of neuro-related protein levels in plasma and link this to human behaviour and disorders.

Cap2 of the cyclic dinucleotide-based anti-phage immune system functions through a ubiquitin-like conjugation mechanism to regulate cGAS activity.

TGF-β can function to increase Treg cell function and reduce anti-tumour immunity. Here the authors show that UDCA is a potential mediator that can reduce TGF-β activity and promote anti-tumour immune responses in mice and can be additive to other checkpoint inhibitors.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Gorman et al. designed a Lassa virus prefusion-stabilized soluble glycoprotein complex trimer (GPC), with which they identified a Lassa virus-neutralizing nanobody that bound the GPC apex and elicited neutralizing antibody responses in guinea pigs.

Recruitment of NLRP3 to the dispersed trans-Golgi network via binding to PtdIns4P is required for activation of the NLRP3 inflammasome by diverse stimuli.

A study leveraging transsynaptic tracing demonstrates rapid and extensive integration of human glioblastoma organoids into the mouse brain.

Research on the link between adherence to specific type of diets and cancer risk is scant, especially regarding overall cancer risk and the mediating mechanisms. Here, the authors use the UK Biobank data to show negative association of adherence to Mediterranean and Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diets with cancer risk and the metabolites mediating this association.

Many diseases can display distinct brain imaging phenotypes across individuals, potentially reflecting disease subtypes. However, biological interpretability is limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Here, the authors describe a deep-learning method that links imaging phenotypes with genetic factors, thereby conferring genetic correlations to the disease subtypes.

FOXM1 is a known transcription factor which promotes cell proliferation in cancer cells. Here, the authors show that FOXM1 is required for the maintenance of quiescence and self-renewal of leukemia stem cells in MLL-AF9-rearranged acute myeloid leukemia patient and mouse models.

Protein expression from circular RNAs is enhanced several hundred-fold by optimizing vector design.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding technique for rare CTCs.

Smad7 controls inflammation by negatively regulating activation of the transcription factor NF-κB. New work shows that Smad7 inhibits NF-κB by binding to the regulatory proteins TAB2 and TAB3, thereby blocking association of the E3 ubiquitin ligase TRAF2 with the kinase TAK1.

Fas signalling induces apoptosis of activated T cells to maintain immune homeostasis. Here the authors show that Fas also induces PKC-β activation to promote NF-κB-mediated T_H9 cell differentiation, while p38 activation by PKC-β antagonizes this effect, thereby supporting a synergy between p38 inhibitor and Fas for T_H9 differentiation.

The germinal centre (GC) response is characterized by regulated production of high affinity, class-switched antibodies in response to T-cell dependent antigens. Here authors show that the GC response is not only regulated at the transcriptional and protein levels, but also by the RNA-binding protein hnRNP F via alternative splicing of the co-stimulatory molecule CD40.

Single-crystal perovskite LEDs exhibit reduced ion migration and Auger recombination and increased device lifetime. Perovskite single-crystals-based LEDs exhibit a maximum brightness of 86,000 cd m⁻², a peak EQE of 11.2% and T₅₀ lifetime of 12,500 h at an initial luminance of 100 cd m⁻².

In this study the authors report USP48 and BRAF are frequently mutated in USP8 wild-type corticotroph adenomas, and cause Cushing’s disease mainly through promoting the promoter activity of POMC. Inhibition of BRAF may be a promising therapeutic strategy for the treatment of patients with BRAF-mutated corticotroph adenomas.

The cGAS–STING signalling pathway, which has a key role in antiviral immune responses in mammals, is found to have originated as an immune-defence system that protects bacteria against viral infection.

Heterotopic ossification (HO) is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these calcified plaques. Here, the authors demonstrate that chemically engineered osteoclasts coated with tetracycline can improve their targeting capacity to ectopic calcifications, which extends their bone resorption functions for the treatment of HO.

Cancer cells exploit immune checkpoint pathways, such as PD-1/PD-L1, to evade elimination by the immune system. Here, the authors demonstrate that TMUB1 regulates post-translational modifications of PD-L1 and that targeting the TMUB1/PD-L1 interaction promotes anti-tumour T cells responses

Quantifying the effects of individual loci on the human phenome is a challenging task. Here, the authors introduce a modelling technique, TGCA, that assesses total genetic contribution per locus and apply this to UK Biobank phenotype domains, revealing top loci and links to tissue-specific gene expression.

Frequency combs, which are important for applications in precision spectroscopy, depend on material nonlinearities for their function, which can be hard to engineer. Now an approach combining magnons and exceptional points is shown to be effective.

The ubiquitin ligase TRAF6 is essential for the activation of NF-κB and MAP kinases in several signalling pathways important for a range of cellular processes including immune function. TRAF6 functions together with a ubiquitin-conjugating enzyme complex to activate the TAK1 kinase complex downstream, which in turn leads to the activation of NF-κB. Here, by reconstituting TAK1 activation in vitro, free Lys 63 polyubiquitin chains are shown to activate TAK1 directly.

The ability of animals to respond to life-threatening stimuli is critical for survival, yet the neural circuits mediating innate defensive behaviors are not well understood. Here, the authors reveal a novel collicular–thalamic–amygdala circuit critical for innate defensive responses to visual threats.

Recent work has demonstrated the potential of polycrystalIine antiferromagnetic materials for spintronics. Here the authors report evidence of magnetic phase transitions in a polycrystalline non-collinear antiferromagnet, which are explained by a phenomenological model with topological orbital momenta.

Autophagy is a cellular process for recycling cell constituents, and is essential for T cell activation, but its function in T cell polarization is still unclear. Here the authors show that autophagy induces the degradation of transcription factor PU.1 to negatively modulate T_H9 homeostasis and antitumour immunity.

Achieving large-area uniform film is the primary challenge to commercialise perovskite LEDs. The authors here employ green binary solvents to regulate the fluidic dynamics in perovskite quantum dot inks during blade-coating to achieve efficient 28 cm2-sized red and white perovskite LEDs.

The application of genome-wide CRISPR–Cas9 screening coupled with a fluorescent reporter to interrogate the microRNA pathway reveals that continual transient phosphorylation of Argonaute 2 is required to maintain the global efficiency of microRNA-mediated repression.

The Armigeres subalbatus sex-determining locus, M, maps to the 3rd chromosome, but its identity was unknown. Here they identify a sex-specific gene, AsuMf, that is essential for male development and show that it is a novel male-determining factor derived from duplication and neofunctionalization of a conserved DBHS family member.

As discussed here, ubiquitylation is involved in many aspects of the immune system, including the innate immune response to pathogens, antigen presentation and the activation of the adaptive immune system. As a result, pathogens have evolved many ways to exploit this form of immune regulation.

A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizophrenia biology.

Bioinks used in current in-situ bioprinting have limitations when applied to complex operational environments. Here, the authors report on the creation of a microgel reinforced GelMA bioink which can be simply prepared and used in different biomedical settings. The application is demonstrated in a cranial defect model.

The cytoplasmic receptor RIG-I recognizes viral RNAs and initiates a protective innate immune response against a number of important viruses. Here, it is shown that RIG-I is regulated by ubiquitination.

The cGAS-STING signalling pathway is critical in mediating host antiviral immunity. Here, Yang et al screen vaccinia viral genes to identify and then characterise that the viral protein E5 is a major inhibitor of cGAS by mediating cGAS ubiquitination and degradation.

The cryo-electron microscopy structure of human TBK1 in complex with cyclic GMP–AMP-bound chicken STING reveals a binding mode that suggests that STING phosphorylation by TBK1 requires oligomerization of both proteins.

Cryo-electron microscopy structures of full-length STING show that cyclic GMP–AMP induces a half-turn rotation of the ligand-binding domain relative to the transmembrane domain, forming a tetramer and higher-order oligomers for signalling.