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CRISPRa screening in primary human cells has remained a formidable technical challenge. Here, the authors developed dCas12f1-SAM and successfully implemented a gain-of-function screen in primary human T cells, identifying key regulators of T cell activation.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

The DAMPE satellite observed a universal charge-dependent spectral softening in primary cosmic rays, and ruled out mass-dependent softening with >99.999% confidence.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

A distinct lipid-laden subset of monocyte-derived macrophages regulates hepatocyte proliferation and liver regeneration in injured livers, via CD36-mediated signalling.

Chen et al. identify a brain-to-bone communication axis whereby extracellular vesicles from aged brain neurons transport WDFY1 protein to distal bone, driving bone-fat imbalance and promoting osteoporosis.

This work reveals an unusual T⁴ temperature dependence of the electronic thermal conductivity at ultralow temperatures and a strong violation of the Wiedemann-Franz law in the topological compensated semimetals TaAs₂, NbAs₂, and NdSb.

Genetic studies of Chinese individuals have been performed, but mostly with short read sequencing, limiting the types of variants that can be identified. Here, the authors perform long read sequencing of 945 han Chinese individuals, finding structural variants under natural selection and those associated with human traits and evolutionary history.

Cationic polymers conventionally kill bacteria via physical membrane disruptions. Here, the authors report the development of carbon acid cationic polymers that show potent activity against multidrug-resistant strains in murine infection models and prevent bovine mastitis, and present evidence that these polymers translocate across bacterial membrane aided by N-heterocyclic carbene.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Ductal lavage represents a treatment option for idiopathic granulomatous mastitis. Here, the authors report the results of a randomized clinical trial, indicating that ductal lavage followed by observation is non-inferior to oral corticosteroids

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.

The central circadian clock in Drosophila is made up of ~ 150 anatomically distributed neurons; the circuits underlying photoentrainment is unclear. This study describes ex vivo patch-clamp recording of the eye-mediated light response of all known circadian clock neurons, and shows that they are organized in parallel circuits centered around a hub.

An ex vivo model and pre-clinical study in a brain-dead recipient provide enzyme-converted O organs to avoid hyperacute rejection in ABO-incompatible kidney transplant patients.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Here, the authors find that the brain recovers during sleep in a hierarchical pattern: higher association areas quiet down while primary sensory regions ramp up during early sleep, with these differences diminishing as slow waves decline.

In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

Understanding the utility of SARS -CoV-2 vaccination platforms and strategies through the emerging pandemic and beyond are critical to understanding the efficacy of such interventions. Here the authors assess nasal delivery of an influenza virus based viral vector for vaccination against SARS-CoV-2 in a hamsters model and assess the induced immunity.

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 genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Preliminary results from a phase 2a trial involving 71 patients suggest that a new agent, discovered and designed with artificial intelligence assistance, is safe and effective for the treatment of idiopathic pulmonary fibrosis.

Polyol oxidation to dicarboxylic acids is hindered by conflicting needs for C–H activation and product desorption. This work resolves the issue using fully exposed Ptn clusters on hydroxyapatite, enabling efficient and selective catalysis.

This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.

Elevated levels of serum IL-6 and TNF-α at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19.

This study presents an oral CRISPR–Cas9 delivery system that precisely disrupts the TRAP1 gene in colorectal cancer, enhancing chemo-immunotherapy with robust antitumour effects.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

Deng et al. expand the toolbox of neurotransmitter sensors with high-sensitivity green and red genetically encoded serotonin sensors. These are suitable for in vivo applications, as demonstrated in a variety of applications in mice.

Membrane proteins are embedded in the lipid bilayer of the plasma membrane and their function in this context is often linked to their specific location and dynamics within the membrane. Here authors report the use of fluorescent magnetic nanoparticles to track membrane molecules and to manipulate their movement and pull membrane components laterally through the membrane with femtonewton-range forces.

In a single-arm phase 2b trial, glecirasib, an oral KRAS-G12C inhibitor, had an overall response rate of 47.9% in patients with locally advanced or metastatic KRAS^G12C-mutated nonsmall-cell lung cancer.

A portable device enables the automated manufacturing of therapeutic-grade biologics in a few hours and under current good-manufacturing-practice conditions.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

How neural crest development is specifically regulated by splicing factors and its vulnerability to splicing dysregulation remains unclear. Here, the authors identify neural crest-specific and somite-specific splicing complexes that confer distinct susceptibility to splicing perturbation.