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There is an unmet medical need for endometrial cancer patients with mismatch-repair proficient disease. Here, the authors report the primary analysis of the FRUSICA-1 phase Ib/II trial evaluating fruquintinib plus sintilimab in this population, showing an ORR of 32.7%, a median PFS of 8.6 months, and manageable toxicity.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

Brown adipose tissue β3AR plays a functional role in regulating susceptibility to social stress, which is controlled by neural inputs from the paraventricular hypothalamus.

The mechanisms underlying the limited response to immune checkpoint blockade (ICB) in most patients remain elusive. This study identifies GBP2 as a key enhancer of T cell-mediated ferroptosis and ICB efficacy through phase separation and STAT1 activation.

Diffuse-type gastric cancer (DGC) accounts for 30% of gastric cancers and has few treatment options. Here the authors present a mutation and proteome dataset for 84 patients, identifying three major classes of DGC and indicating potential targets for therapy.

Membranes selective to ions of the same charge are sought for water waste processing and valuable element recovery. Here authors show that ions intercalated into vermiculite laminate membranes become effectively unexchangeable, creating stable channels that exhibit robust and tuneable ion selectivity.

The clock regulator TIME FOR COFFEE is found to interact with core clock components to form a ‘Morning Complex’ which represses a group of genes including PHYA and other phyA signaling components particularly at dawn in Arabidopsis.

To address the shortcomings in the application of bioactive peptides as drugs, incorporation of unnatural amino acids (UAAs) has been used. Here, the authors report an ionic compound-promoted C-N cleavage of alkyl pyridinium to generate alkyl radicals upon excitation by visible light, and apply it for deaminative hydroalkylation of alkenes to synthesise diverse β-alkyl substituted UAAs.

The interactions of CAR-T cells and solid tumors are modeled on a chip.

RNA-binding proteins (RBP) have been implicated in the regulation of inflammation, but mechanistic insights are still lacking. Here the authors profile RPBs to find ribosomal RNA processing 1 binding to thymidylate synthetase (TYMS) RNA to suppress TYMS expression and dampening macrophage one-carbon metabolism to suppress innate immunity.

C-N bond forming is an established strategy to form amines, which are quintessential in chemical synthesis and in nature. Here, the authors report three classes of photoredox reactions, involving C(sp³)-N coupling between N-centered radicals and alkyl radicals and C(sp³)- C(sp³) coupling via C(sp³)-H alkylation.

CIGS is a high-resolution dataset comprising chemical perturbation-induced 319,045,108 gene expression events.

Brassica oleracea is plant species comprising economically important vegetable crops. Here, the authors report the draft genome sequence of B. oleracea and, through a comparative analysis with the closely related B. rapa, reveal insights into Brassicaevolution and divergence of interspecific genomes and intraspecific subgenomes.

Cryo-EM structures and quantum calculation reveal LHCII as a controlling switch for the transition between light capture and excess energy dissipation, in response to lateral pressure and acid-induced conformational changes.

In large prospectively enrolled validation cohorts of patients with cancer and controls and a prospective study of asymptomatic individuals with average risk for cancer, a multicancer early detection test based on plasma cell-free DNA genomics and fragmentomics showed encouraging accuracy in identifying ongoing disease as well as the tissue of origin.

The authors develop a scalable reactive sintering method to produce ZrNiSn-based thermoelectrics without melting, achieving a high zT of 1.33 at 873 K through hierarchical microstructure engineering and detailed property analysis.

Yang et al. show an age-related increase in the microbial-derived metabolite phenylacetylglutamine that drives host cellular senescence by inducing DNA damage and mitochondrial dysfunction via ADR–AMPK signaling.

Xiaowu Wang, Jian Wu, Guusje Bonnema and colleagues report resequencing and subgenome selection analysis of 199 Brassica rapa and 119 Brassica oleracea accessions representing diverse morphotypes. They identify 4 subgenome loci with evidence of parallel selection among subgenomes and 15 subgenome loci with evidence of parallel selection between species.

Cao and colleagues show that the RNA-binding E3 ligase MKRN2 selectively inhibits the translation of Il6 messenger RNA in activated macrophages.

Here the authors elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offers potential therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

Gastrointestinal stromal tumours (GISTs) are clinically heterogeneous, with varying degrees of aggressiveness. Here, the authors describe the genomic and transcriptomic landscape of 117 GISTs from 105 patients; they find four molecular subtypes as well as recurrent inactivating YLPM1 mutations in high-risk/metastatic GIST.

Tracing cellular changes in complex biological systems is challenging. Here, authors present a flexible framework that integrates multi-sample data with in-house algorithms to infer comparative and spatiotemporal cell-gene patterns, advancing understanding of cellular dynamics.

In this study, the authors develop a potent bispecific antibody targeting two epitopes within the SARS-CoV-2 receptor binding domain and showing robust prophylactic and therapeutic efficacy against XBB.1 infection in mice.

This study on the genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies macaque models for inherited human retinal and neurodevelopment diseases.

The efficacy of drug-eluting stents remains limited due to delayed reendothelialization, impaired intimal remodeling, and potentially increased late restenosis. Here the authors propose a one-produces-multi stent coating, a drug-free strategy that supports in situ healing of vascular tissues, as demonstrated in rabbit and porcine models.

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

Channelrhodopsins’ mechanism of light-gated ion conductance could be engineered for use in optogenetic tools. Here, structures of the slow-cycling mutant of HcKCR1, including an open state structure, provide insight into channel gating and selectivity.

The thermoelectric material Mg₃Bi₂ is shown to be ductile in single-crystal form along certain directions, with a room-temperature tensile strain of 100%, which is attributed to the gliding of dislocations.

The study identifies TaSPL6-D as a negative regulator of TaHKT1;5-D and salinity tolerance in bread wheat. An insertion variation of TaSPL6-D, mainly hidden in landraces, shows the potential for breeding salt-tolerant crops.

Circadian pace is modulated by light intensity. Here the authors show that CRY2 interacts with PRR9 to mediate blue light input to the circadian clock and is degraded at higher light intensity offering a mechanistic explanation as to how intensity can modify clock place.

A signalling mechanism ensuring intraspecies and interspecies reproductive barriers in flowering plants is uncovered.

AgRP neurons in the hypothalamic arcuate nucleus (ARH) are involved in regulating hunger and energy balance. Here the authors show that knockout of the DNA methyltransferase Dnmt3a in AgRP neurons of the ARH leads to a reduction in voluntary exercise along with numerous epigenetic and gene expression changes in ARH neurons.

Beta cell dysfunction and reduction in beta cell mass are hallmark events in the pathogenesis of diabetes mellitus. We identify focal adhesion protein Kindlin-2 as a key factor that controls insulin synthesis and secretion and beta cell mass by modulating MafA and beta-catenin proteins in pancreatic beta cells.

Quorum sensing is a regulatory mechanism controlling bacterial signaling and ComA, a conserved efflux pump, is responsible for the maturation and secretion of peptide signals. Here, authors determine the 3D structure and demonstrate its function as an ABC transporter.

A dominant genic male sterility (DGMS) mutant of Brassica oleracea was identified in 1970s and has been widely used for hybrid cabbage breeding, but its genetic basis is unclear. Here, the authors reveal that a 1-bp deletion in the promoter of the gene encoding a PHD-finger motif transcription factor is responsible for DGMS.

Vacancy has only played a stereotyped role as a scattering center in thermoelectrics, and the boundaries of its versatility have not been tested. Here, authors reveal the multifunctionality of vacancy in tailoring the phononic and electronic transport in a defective half-Heusler ZrNiBi.

Connecting the different layers in thermoelectric modules is challenging. Yin et al. develop a low-temperature-sintered silver nanoparticle interlayer for high-temperature operation of devices based on a variety of thermoelectric materials.

Recently discovered kalium channelrhodopsins (KCRs) are optogenetic tools for neuronal silencing. Here, authors report cryo-electron microscopy structures of KCR1 from Hyphochytrium catenoides and a highly homologous but sodium-selective channel from the same organism.

ATG9 is the only transmembrane protein of the core autophagy machinery known to be present at presynapses. Here, the authors show that both synaptophysin and ATG9A vesicles assemble into condensates with synapsin but remain segregated from each other.

Zhang et al. perform single-cell RNA and B-cell receptor sequencing to characterize the transcriptomic profiles of B-cell acute lymphoblastic leukaemia cells at diagnosis, residual and relapse stages, uncovering the hypoxia pathway as a potential target for residual leukaemia cells.