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Here, in a clinical trial, the authors show that CFTR-modulator therapy reshapes the lung and gut microbiomes in cystic fibrosis, reducing bacteria such as Staphylococcus in the lungs and Escherichia in stool, and showing that microbiome dysbiosis can be partially reversed.

In this work, authors explore the potential of strain-specific commensal E. coli in their ability to inhibit multi-drug resistant Enterobacterales via nutrient competition. Their findings highlight the potential of rationally designed metabolically complementary probiotics for targeted gut decolonization of antibiotic-resistant bacteria.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Here, the authors apply a standardized system, called TXsystem, to transplant wild mouse gut microbiota into SPF mice, developing “TXwildlings” mice that stably retain natural microbiota and human-like immune traits, enhancing reproducibility and translational relevance.

Effusive volcanism dominates at water depths of 300 m or greater while phreatomagmatic Surtseyan eruptions become prevalent at shallower depths, according to analyses of high-resolution seismic reflection profiles, multibeam bathymetry, and seafloor imagery.

Characterizing higher order nonlinearities and responses to optical excitations in materials is challenging. Here, the authors use high harmonic generation in sapphire crystals to extract higher order susceptibilities and characterize the nonlinear electronic response directly from experimental measurements.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Super-rotors are fast rotating molecules whose rotational–translational energy transfer is suppressed. Here the authors study the equilibration of super-rotor gases through molecular dynamics simulations, showing the emergence and explosive termination of an anisotropy in the molecular angular distribution.

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

The authors demonstrate in a mouse model that Western-style diets synergize with antibiotics to impair microbiota function. In turn, Klebsiella oxytoca promotes post-antibiotic microbiota recovery and removal of the pathogen Klebsiella pneumoniae.

Malnutrition is a key risk factor affecting children’s health and development. Here, the authors report long-term protection against malnutrition-induced enteropathy by a neonatal S100a8/a9 nutritional supply in mice.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Melanocortin-4 receptor (MC4R) is key in controlling hunger. Here, authors discover the MC4R-specific, potent agonist nanobody pN162. The pN162-MC4R-Gs-Nb35 structure shows its distinct binding mode compared to peptide agonists.

Insulin secretion adapts to metabolic needs, but how this happens over the short term is not clear. Here the authors show this involves upregulation of beta-cell exocytosis and requires the SUMO-protease SENP1, which responds to redox state in a zinc-dependent manner.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.

A large-scale multi-omics analysis reports oncogenic alterations that drive medulloblastoma progression, rather than initiation, and the findings show how single-cell technologies can be used for early detection and diagnosis of medulloblastoma.

A computational pipeline linking molecular dynamics simulations and an elastic network model-based method identifies druggable sites in the parathyroid hormone class B GPCR and a nonpeptidic allosteric modulator of receptor signaling in cells.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

The antisense oligonucleotide rugonersen has acceptable safety and tolerability in children with Angelman syndrome and shows partial normalization of electroencephalogram abnormalities and clinical improvements relative to natural history.

Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.

Klebsiella oxytoca provides protection against Salmonella Typhimurium via toxin-dependent inhibition in nutrient-rich, low-competition environments but switches to substrate-driven competition when nutrients are limited.

Muscle undergoes hypertrophy and atrophy in response to physiological stimuli or in pathological conditions, which is partially controlled through altered gene expression. Here the authors report that m⁶A methyltransferase METTL3 and mRNA m⁶A post-transcriptional modifications as a mechanism that regulates muscle hypertrophy and atrophy via myostatin signalling in mice.

Lava planets are tidally locked exoplanets with molten daysides. Simulations show that their interior state—fully molten or with a shallow magma ocean—affects the atmospheric composition and surface dynamics, and can be probed with JWST.

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.

Current strategies for protein encapsulation in DNA vessels for controlled enzymatic catalysis or therapeutic delivery rely on formation of covalent complexes. Here, the authors design a system that mimics natural reversible non-covalent host–guest interactions between a DNA host and the protein DegP.

In the kidney, maintaining permeability of the filtration barrier is critical. Here, Sachs W. et al show that homeostasis of podocytes and glomerular endothelial cells relies on differing proteasome constitutions which orchestrate endocytic activity in addition to protein degradation.

Leprosy, caused by infection with Mycobacterium leprae, was common in Europe in the Middle Ages. Here, Krause-Kyora et al. analyze ancient DNA from a medieval Danish leprosarium to assemble 10 complete bacterial genomes and perform association analysis of the DRB1*15:01 allele with risk of leprosy infection.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Using survey data from over 3 million individuals, Geldsetzer et al. present evidence for cardiovascular disease risk factors among individuals living in extreme poverty in low- and middle-income countries.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Steatohepatitis is a chronic hepatic inflammation associated with increased risk of hepatocellular carcinoma progression. Here the authors show that intestinal dysbiosis in mice lacking the inflammasome sensor molecule NLRP6 aggravates steatohepatitis and accelerates liver cancer progression, a process that can be delayed by antibiotic treatment.

Somatic variants in certain genes can cause lesional focal epilepsy. Here the authors perform the largest somatic variant detection study in epilepsy to date, finding statistical support for 8 known and 2 novel genes, DYRK1A and EGFR, which may be potential biomarkers and druggable targets.

γδ T cells are known to recognize phosphoantigen in the context of butyrophilins (BTN), yet the molecular rules underlying this phenomenon are unclear. Here, the authors demonstrate that a distinct topology of B30.2 and IgV domains within BTN3A complexes promotes antigen sensing and that the juxtamembrane region controls BTN complex formation.

Here, Schoeler et al. investigate how interaction between dietary lipids and the gut microbiota affect hepatic steatosis and host metabolism, showing that dietary lipids impact the gut microbiota composition independent on fiber intake in humans and mice.

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors characterise these features of the immune response using data from a large representative community sample of the UK population.

Microbial communities provide protection to their hosts by excluding colonizing pathogens. Here the authors study plasmid transfer and plasmid-mediated effects on host colonization and persistence of Enterococcus faecalis in the intestinal tract of mice.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

Innate lymphoid cells (ILC) are important immune cells for maintaining the gut homeostasis. Here the authors show that c-FLIP, an anti-apoptotic molecule, is important for the development of NKP46⁺ ILC1, including conventional natural killer (cNK) cells, and ILC3, with cNK being more critical for ameliorating intestinal inflammation.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

GtACR1 harbors a second, “O-state” photoactivatable branch: light can re-excite the all-trans retinal–containing O intermediate to reopen the channel almost immediately, sustaining large anion currents without the inactivation seen in ChR2.

Knabl et al. perform a seroepidemiological study in the Austrian ski resort Ischgl, where a super-spreader event lead to a SARS-CoV-2 outbreak. Through mathematical modelling, they find that the subsequent decline in viral transmission was most likely a combined effect of high seropositivity and the implementation of non-pharmaceutical interventions.