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This prospective cohort study of patients with cancer incorporated antemortem follow-up visits and rapid autopsy analyses, and reports that spikes—rapidly increasing levels—of circulating tumor cell clusters, observed immediately before and at the time of death, along with tumor masses infiltrating large vessels, were cancer-related events associated with patient mortality.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and loss of kidney function, yet prognostic biomarkers remain limited. Here, the authors show that serum proteomics identifies protein signatures associated with disease severity, enabling improved risk prediction and stratified management.

A deterministic correction of errors caused by qubit loss or leakage outside the computational space is demonstrated in a trapped-ion experiment by using a minimal instance of the topological surface code.

The dynamics of microglia states adjacent to or far from amyloid-beta plaques are unclear. Here the authors show that non-plaque-associated microglia modulate the cell population expansion in response to amyloid deposition, and Csf1 signaling regulates their transition to the amyloid-associated state.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Carcinoma subtypes are normally linked to specific genetic alterations, but tissue mechanical changes also play a role. Now, aberrant morphologies resembling bladder carcinoma are shown to emerge from stiffness changes during epithelial overgrowth.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Achiral minerals often adopt a chiral shape when crystal growth proceeds in contact with chiral molecules. Now, detailed microscopic insight is provided into how the chiral footprint of hemifullerene (a buckybowl that is essentially half of C₆₀) rearranges atoms at step edges on a copper surface into chiral motifs.

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.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

A fault-tolerant, universal set of single- and two-qubit quantum gates is demonstrated between two instances of the seven-qubit colour code in a trapped-ion quantum computer.

There is a limited endogenous subventricular zone (SVZ)-derived neurogenic response for brain repair. Here, the authors report that cortical stroke-evoked environmental changes in the SVZ alter microglia-neural stem/precursor cells cross-communication, limiting the neurogenic repair response.

High salt intake changed the gut microbiome and increased T_H17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T_H17 cells and increased blood pressure in humans.

Pulmonary carcinoids account for about 2% of pulmonary neoplasms. Here, the authors carry out gene copy number analysis, genome/exome, and transcriptome sequencing of pulmonary carcinoids and identify frequent mutations in chromatin-remodelling genes that can drive tumorigenesis in these tumours.

Ferroptosis is a regulated form of cell death occurring upon lipid peroxidation. Here, the authors discovered that activation of the Farnesoid X receptor by bile acids suppresses ferroptosis through upregulation of anti-ferroptotic genes.

Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

ALS is somewhat heritable, but the genetic basis is not completely understood. Here, the authors identify alterations in splicing in neurons associated with amyotrophic lateral sclerosis and uncover several associated genetic loci, with a potential link to nuclear pore defects.

Increases in transcriptional elongation speed with age affect organismal lifespan and ageing-related changes could be reversed with lifespan-extending interventions.

The authors studied the function of a PIN gene in a filamentous charophyte green alga (Klebsormidium flaccidum). They found that the plasma membrane auxin efflux function is an early trait that emerged before divergence between algae and land plants.

SUMOylation is a post-translational modification that has been shown to be altered in cancer. Here, the authors show that loss of the SUMO isopeptidase SENP6 leads to unrestricted SUMOylation and genomic instability promoting lymphomagenesis and generating vulnerability to PARP inhibition.

SARS-CoV-2 mutations associated with the escape from antibody-mediated neutralization have been widely reported. Here, in a patient with defective antibody responses, the authors find a potential association between SARS-CoV-2 mutations and CD8 T alterations to implicate possible contributions of CD8 T cells in evasion of SARS-CoV-2 from host immunity.

Researchers demonstrate a laser interferometer that achieves simultaneous nonclassical readout of two conjugated observables. Because their system uses steady-state entanglement, it does not require any conditioning or post-selection. By distinguishing between scientific and parasitic signals, its sensitivity exceeds the standard quantum limit by about 6 dB.

Recent years have seen significant progress in the coherent control of collective excitations such as magnons and phonons in quantum materials using ultrafast laser pulses. Here the authors report evidence of coherent excitation of orbitals in a rare earth pyrochlore spin liquid material Tb2Ti2O7 by THz pulses.

Age impacts the effect of dietary health and longevity interventions but the underlying mechanisms are incompletely understood. Here the authors study fasting in killifish and find that older animals exhibit a metabolic shift resembling a fasting-like program, which is counteracted by boosting the activity of AMPKγ1, promoting health and longevity.

The spatial organization of cell surface receptors is critical for cell signaling and drug action. Here, the authors develop an optoproteomic method for mapping surface protein interactions, revealing cellular responses to antibodies, drugs and viral particles as well as immunosynapse signaling events.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

Wang, Philpott et al. perform integrative genomic, transcriptomic and proteomic analyses across fibroid, myometrium, and endometrium tissues to uncover mechanisms underlying uterine fibroid (UF) associated heavy menstrual bleeding. Signalling from MED12-mutated fibroids alters RNA splicing events in the endometrium.

Astrocytes play important roles in neuroinflammatory diseases. Here the authors characterize human glioblastoma-associated astrocytes by gene expression and demonstrate their immunosuppressive role promoted by interactions with tumor and microglia cells in an organotypic model.

Genomic sequencing of 110 human small cell lung cancers identifies genomic signatures including nearly ubiquitous bi-allelic inactivation of TP53 and RB1, a role for NOTCH family genes, and somatic rearrangements that create an oncogenic version of TP73.

Conserved microbiome features across clinical and geographical variations may enable microbiome-based predictions of outcomes in CD19-targeted CAR-T cell immunotherapy

Two-photon calcium imaging reveals that the mouse retina contains more than 30 functionally distinct retinal ganglion cells, including some that have not been described before, exceeding current estimates and suggesting that the functional diversity of retinal ganglion cells may be much larger than previously thought.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Animal lifespan is plastic and is regulated by conserved signalling pathways. Here, Tikuet al.show that longevity-enhancing mutations or interventions are associated with reduced nucleolar size in worms, flies, mice and humans, and that nucleolar size can predict life-expectancy in individual worms.

While rheology studies have contributed to the understanding of the viscoelastic properties of living cells, the use of higher frequencies promises elucidate the link between cellular and molecular properties. Here authors introduce a rheological assay that measures the cell mechanical response across a continuous frequency range ≈ 1 – 40 kHz.

The molecular nature of large-cell neuroendocrine lung carcinomas (LCNEC) has remained unclear. Here, the authors show LCNECs represent a distinct transcriptional subgroup among lung cancers and comprise two molecular subgroups, type I (TP53 and STK11/KEAP1 alterations) and type II (TP53 and RB1 inactivation).

The expression of oncogenic MYC paralogs in small cell lung cancer is mutually exclusive. In this study, the authors show that MYC, but not MYCN or MYCL, represses BCL2, resulting in cells that are uniquely sensitive to apoptosis, and find that CHK1 and AURKA inhibitors may be useful for treating these cancers.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

G-protein-coupled receptors (GPCRs) transmit signals through intracellular heterotrimeric G proteins and arrestins. Here, Szczepek et al.present the structure of a common binding interface for Gα and arrestin on rhodopsin to shed light on key interactions that mediate transduction of specific signals through a single GPCR.

By performing experiments under upper tropospheric conditions, nitric acid, sulfuric acid and ammonia can form particles synergistically, at rates orders of magnitude faster than any two of the three components.

The tumour microenvironment counteracts immune therapy in Glioblastomas. Authors show here, using spatially resolved and single cell transcriptomics, that dysfunctional T cells are induced by a myeloid cell subset via Interleukin-10 signalling, and inhibition of the downstream JAK/STAT pathway might restore glioblastoma immune therapy responsiveness.

This resource presents a high-resolution diffusion MRI dataset of a chimpanzee brain, which should be useful for evolutionary studies of primate brain evolution.

Roman Thomas and colleagues report exome sequencing of 29 small-cell lung cancers (SCLCs), 2 SCLC genomes and transcriptomes of 15 SCLCs. They identify recurrent mutations in the CREBBP, EP300 and MLL genes encoding histone modifiers. They identify mutations in SLIT2 and EPHA7, which have a role in axon guidance and cell migration, and focal amplifications of FGFR1.