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An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

The authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

Coagulase-negative staphylococci secrete natural products that prevent pathogen colonization. Here, the authors identify hominicin, a daptide bacteriocin produced by Staphylococcus hominis that has antimicrobial activity against a skin pathogen.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

Intramolecular coupling of extended biphen[n]arenes is developed to yield cycloparaphenylenes (CPPs). The modular nature of biphen[n]arenes makes it possible to customize CPP structures, which permits tuning of their photophysical properties. The syntheses are short and excellent yields are achieved. Moreover, postsynthetic functionalization is possible.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this work authors demonstrate how photocontrolled tag-targeted degradation enables precise, spatiotemporal control of protein expression in tumor cells and CAR T cells, offering an esapproach for regulating engineered proteins with light.

A growing number of compounds are reported to extend lifespan, but it remains unclear whether they reduce mortality across the entire life course or only at specific ages. Here the authors introduce an analytic tool that pinpoints when, for how long, and to what extent presumptive anti-aging treatments alter mortality risk.

Royer and colleagues find a principal dimension of neural dynamic similarity dissociating unimodal and association cortices. Systematic variations in local and macroscale constraints across the cortex also followed this pattern.

How chemotherapeutic nucleoside 6-thio-2’-deoxyguanosine (6-thiodG) targets telomerase to inhibit telomere maintenance in cancer cells and tumors was unclear. Here, the authors show that telomere length and telomerase status determine 6-thio-dG sensitivity and uncover the molecular mechanism by which 6-thio-dG selectively inhibits telomerase synthesis of telomeric DNA.

The European Commission has set a regulatory benchmark for classifying green hydrogen in the European Union. New research finds that by regulating the power purchase for electrolysers, emission savings from green hydrogen production is ensured, but cost is also affected.

Metazoans have evolved endocrine systems that signal through dimerized receptors in response to cognate hormones. These authors characterize a nematode homolog of such human receptors, presenting the cryo-EM structure of an asymmetric dimer that embodies properties of the human receptors.

Here, the authors show that brain dynamics mature from childhood to adulthood with increased hierarchical propagation and reduced visual-somatomotor dynamics. Top-down hierarchical flow strengthens throughout this developmental period.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Eutrophication and chlorophyll-rich algal blooms occurred at high concentrations of the thermoplastic polyurethane, but only occasionally with bioplastics, suggests a three-month experiment exposing plankton in experimental ponds.

Light represses biofilm formation and production of virulence factors in the pathogenic bacterium Pseudomonas aeruginosa. Here, Manias et al. identify a periplasmic microprotein that regulates this process by activating the degradation of a component of the light-sensing pathway.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

Biofluorescence is widespread in fishes. Here, the authors compile data on biofluorescence presence across teleost fishes and demonstrate that it may have originally evolved in eels 112 million years ago, but evolved numerous other times as well, often in association with coral reefs.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Exotic six- and eight-particle excitonic complexes have recently been observed in 2D semiconductors. Here, the authors uncover a stable many-body exciton in WSe₂–comprising 20 interacting quasiparticles–that emerges when strong electrostatic doping fills the Q valley.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

Scaffold-guided bone regeneration is a promising treatment strategy for segmental defects, but clinical translation has been hindered, partially by mechanical function limitations. Here, Clark et al. describes a permanent printed polymer with a resorbable stem cell laden ceramic core for reconstructing segmental mandibular defects, which is tested in an ovine model.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Experiments with human volunteers and macaques show that expectations produced by probabilistic cueing of future sensory inputs shape motor circuit dynamics in order to increase the efficiency of movement responses.

Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lunapark protein and is modulated by nutrient status.

Activity-based protein profiling identifies covalent small molecules that potentiate the activity of the METTL5:TRMT112 complex through binding to a complexoform-restricted allosteric pocket absent in other TRMT112:methyltransferase complexes

Drug combination discovery remains slow and challenging. Here, the authors introduce Combocat, an open-source framework that combines acoustic liquid handling protocols with machine learning to achieve ultrahigh-throughput drug combination screening; as proof of concept, they use Combocat to screen 9,045 drug combinations in a neuroblastoma cell line.

The common description of strong-field light–matter interaction neglects the quantum-optical nature of the driving field. Now signatures of strong-field photoemission appear in electron energy spectra when driving with non-classical light.

Authors show that all individuals have asymmetrically glycosylated IgGs—the glycans on each of the Fc protomers are not identical. Asymmetrically monofucosylated IgGs drive dengue disease and are functionally similar to afucosylated IgGs.

The factors governing mouse decision-making strategies in changing environments remain unclear. Here the authors use a 4-state input-driven model to show that past stimuli/choices drive switches in bias, while past rewards drive switches in engagement.

Mismatch repair pathway is frequently dysregulated across cancer types, commonly represented by loss of MLH1 or MSH2 gene expression. Here the authors model MLH1 missense mutations from patients to study how cytoplasmic localization of MLH1, promotes resistance to endocrine therapy but predicts response to cell cycle inhibitors in breast cancer.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Targeted protein degradation using PROTACs doesn’t discriminate functional from disease-causing versions of the same protein. Here, we describe small molecule TRIMTACs that recruit the unique E3 ligase TRIM21 and allow state-selective protein degradation, including challenging substrates like tau.

Barcoding microbial ribosomal RNA creates a recording of gene transfer events without requiring translation.

Here, the authors characterize the gut virome of 647 one-year-old children in the COPSAC2010 cohort, finding that anelloviruses are highly prevalent and associated with daycare attendance, gestational age, and FUT2 secretor status.

Rotors are widespread in nature, but the collective behavior of heterogeneous populations remains poorly understood. Authors demonstrate that oppositely spinning rotors spontaneously self-assemble into active chains called gyromers, stabilized purely by fluid and steric interactions.

Rizzollo et al. show that BDH2 participates in iron distribution between cellular compartments, which sets the threshold for the ferroptosis vulnerability of the melanoma cell phenotypes, ultimately affecting their metastatic capacity