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In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Humans rely on both learned value and action affordances to decide how to act. This study shows that these systems compete under a dynamic brain controller, with the presupplementary motor area and anterior cingulate cortex guiding which system dominates.

Natural rubber is a widely used biopolymer and further improving its resistance to crack growth will extend its service life. Here the authors show a strategy to amplify the resistance to crack growth in natural rubber by forming a tanglemer.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

The Greenland shark, the longest-living vertebrate, inhabits the dim, frigid depths of the Arctic Ocean. Despite its extreme lifespan, this study finds that its vision remains intact and well-adapted for life in dim light, revealing remarkable preservation of sensory function across centuries.

The inability of intrinsically photosensitive retinal ganglion cells to shift the circadian clock in the suprachiasmatic nucleus during daytime is caused by light-dependent depolarization block of these cells.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

De novo domestication was performed on the brassica Thlaspi arvense (pennycress) by identifying and stacking CRISPR-induced mutations to create a new intermediate oilseed crop that can be grown in the off-season, with seed compositions similar to canola (low erucic acid and reduced glucosinolate).

T cells can recognise lipid antigen in the context of CD1d molecules. Here, the authors show that γδ T cell activation in response to CD1d differs from that of αβ T cells and determine the structure of a γδ T cell receptor that binds to CD1d independently of the presented lipid.

In this study, researchers show that season and exposure to light affect different nuclei of the amygdala and that these effects are related to mood. This may explain in part the benefits of light therapy for mood disorders.

Zhao et al. generated models from whole blood gene expression to predict amyotrophic lateral sclerosis case-control status and combined gene features with clinical variables to predict survival, both validated in an external independent dataset.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.

Researchers applied high resolution inversions of satellite methane observations to estimate methane emissions from 161 countries, finding that global anthropogenic emissions are 15% larger than Paris Agreement reporting.

Using activity-based chemical probes, oncogenic IDH1-R132H but not the wild type was found to acquire a unique autopalmitoylation at C269. This mutant-specific modification is critical for the enzyme’s abnormal activity in cancer.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

Herpesvirales utilize a unique nuclear egress route for capsid export. Here the authors show that herpesviruses exploit a cellular membrane protein, once thought to transport chloride, to facilitate membrane fusion and egress from the nucleus.

Gallium phosphide (GaP) is explored as a promising material for supercontinuum generation. The authors demonstrate an octave-spanning supercontinuum in the anomalous-dispersion regime and substantial spectral broadening performance in the normal dispersion regime within a sub-millimeter GaP waveguide.

Here they combine in vivo imaging with proteomics to characterize a protein complex comprised of Ccdc78 and Ccdc33 that acts at the extreme distal tip of 9 + 2 motile cilia to control tip architecture, cilia length, and cilia beating.

A hidden Markov model that uses probabilistic retrospective inference allows for up to one month of unsupervised recalibration in an online cursor-based intracortical brain–machine interface.

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.

Tree longevity is thought to increase in harsh environments, but global evidence of drivers is lacking. Here, the authors find two different pathways for tree longevity: slow growth in resource limited environments and increasing tree stature and/or slow growth in competitive environments.

The authors demonstrate dual-probe multi-messenger imaging of high-energy-density plasmas based on laser-wakefield-accelerated electrons. This enables spatiotemporally resolved simultaneous probing of plasma hydrodynamics and electromagnetic field evolution with both x-ray and electron beams.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

This paper describes the Simons Sleep Project, an open resource designed to accelerate research into the sleep and daily behaviors of autistic children using synchronized recordings from multiple wearable and nearable devices for >3,600 days and nights.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

GRX-810, an oxide dispersion strengthened alloy, shows excellent structural performance above 1100°C and stability up to 1300 °C. Grain-size effects, additive manufacturing–induced anisotropy, and fine trigonal Y₂O₃ particles enhance creep resistance.

SmartEM is a ‘smart’ pipeline for electron microscopy-based data acquisition for connectomics. In order to efficiently image large datasets, the approach involves imaging at short pixel dwell times and identifying problematic regions that are then imaged with longer dwell times and therefore higher quality.

Through next-generation spectral analysis, scientists have uncovered an evolutionary path for Wolf–Rayet stars in metal-poor environments. Characterized by hard ionizing radiation, these stars challenge current assumptions about massive star evolution.

Marine darkwaves can be used to compare patterns and ecological consequences of episodic light reduction in marine ecosystems, according to application of the framework to both in situ and satellite based light irradiance data from California and New Zealand.

Long-read sequencing enables high-quality genome assemblies, but challenges remain. Here, the authors introduce Cornetto, a method that improves assembly quality, enables genome sequencing from saliva, and accurately resolves medically-relevant repetitive genes.

cAMP export by ABCC4 is critical for localized signaling. Here, the authors revealed that PKA activation drives ABCC4 to the plasma membrane and organizes a PDZ-dependent protein network with actin cytoskeleton and scaffolds, like SCRIB, that stabilize the transporter and optimize cAMP efflux. Furthermore, the authors show that the potent ABCC4 inhibitor Ceefourin 2 disrupts this network, revealing a non-canonical mechanism of ABCC4 inhibition.

mRNA COVID-19 vaccines have been updated to the SARS-CoV-2 KP.2 variant of concern, due to its emergence in early 2024. Using data from the US Veterans Affairs Healthcare System, the authors here estimate that the BNT162b2 KP.2-adapted vaccine is 56‒68% effective at preventing a range of COVID-19 outcomes during the early part of the 2024–2025 respiratory virus season.

The hippocampus can replay long spatial sequences without ripples. When present, ripples cluster in spatially restricted zones as a function of replayed location that remap with barrier changes, implying a tagging role in consolidation.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

PPARγ regulates glucose and lipid metabolism, yet safer PPARγ-targeted insulin sensitizers are needed to treat metabolic disorders. Here, Kuang-Ting et al. elucidate structure–function relationships of non-covalent inverse agonists that enhance receptor binding and improve insulin sensitivity, providing a framework for next-generation drug design.

Interregional transmission is key to a cost-efficient, reliable and cleaner US grid. Senga et al. find that current legislative proposals can increase reliability while capturing some of the cost and emissions benefits of a cost-optimized grid.