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A deep generative model is developed for de novo molecular design and optimization by leveraging electron density. Wet-laboratory assays validated its reliability to generate diverse bioactive molecules—orthosteric and allosteric, inhibitors and activators.

Perez, Kimoto, Rajakumar and colleagues present a fast and accurate DNA sequencing method that reads canonical and non-canonical bases using AI and nanopore technology. The approach enables an expanded genetic alphabet for data storage, nucleic acid therapeutics and synthetic biology.

The production of hematopoietic stem cells in the embryo is precisely regulated by various intrinsic and extrinsic factors. Here, the authors find that autophagy is involved in the maturation of hematopoietic precursors through nucleolin pathways.

Alternating copolymerization of cyclic anhydrides and epoxides is an interesting platform for the synthesis of polyesters from renewable resources, but the near irreversibility of the copolymerization makes it challenging to develop chemically recyclable polyesters with easy-to-tune structure. Here, the authors develop a recyclable polyester library from alternating copolymerization of aldehyde and cyclic anhydride.

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.

A gene-edited pig liver transplanted into a human recipient remains functional after 10 days and indicates that porcine organs could help meet the growing demand for liver transplants.

Bringing together p- and n-type monolayers of semiconducting transition metal dichalcogenides results in the formation of atomically thin pn junctions. Here, the authors laterally manipulate carrier density to create a WSe₂ pn homojunction on a supporting ferroelectric BiFeO₃ substrate.

Although most patients achieve complete response after standard-of-care treatment, residual disease in patients with nasopharyngeal carcinoma is associated with poor prognosis. Here the authors report the results of a phase 2 trial of toripalimab (anti-PD1) plus capecitabine for patients with residual nasopharyngeal carcinoma.

Tetrasubstituted alkenes have found use due to their potential photophysical properties. Here the authors present a method to form tetrasubstituted vinyl sulfides via a rhodium carbenoid rearrangement.

Thin films of halide perovskites are promising for solar cell technology but they do not perform well at the band edge due to the low optical absorption. Herein, Chen et al. fabricate a high efficiency single crystal perovskite solar cell with thicker single crystals to harvest the below-bandgap photons.

This study shows how auditory cortex activation and cognitive function develop during a six-month follow-up after gene therapy in children with congenital deafness.

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.

MPHOSPH8 loss inhibits acute myeloid leukemia (AML) development by reactivating LINE-1 retrotransposons. LINE-1 suppression is associated with therapy resistance and poor prognosis in patients with AML.

Age is closely related to health, but chronologically defined age often disagrees with biological age. Here, the authors develop an indicator of biological age - LensAge index - to reveal individuals’ aging level, and it can be implemented with smartphones, showing potential for self-monitoring of aging.

Cytology is commonly used for cervical cancer screening or triage. Here, the authors used deep learning to develop a liquid-based cytology screening approach to detect cervical cancer in both community and hospital-based settings.

Zheng and colleagues report that targeting both the death domain and the paracaspase domain of MALT1 with antisense oligonucleotides sensitizes resistant tumors to immune-checkpoint inhibition.

Transcription factors are crucial in disease but hard to target with traditional drugs. Here, authors present BlockerSELEX, a strategy to develop inhibitory aptamers that block transcription factor interactions, which disrupts interactions between key proteins, showing potential for new nucleic acid therapies.

Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here the authors introduce Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data.

Existing organic long-persistent luminescence systems do not align with human scotopic vision. Here, authors achieve blue-shifted emissions in binary systems by upconverting charge-transfer to locally excited singlet state, with a strong luminescence under international standard for safety signs.

A large integrated genome and transcriptome analysis of colorectal cancer identifies prognostic mutations and expression subtypes.

The authors showcase a photonic tensor core in TFLN platform that achieves a computational speed of 120 GOPS for neural networks, with capabilities of in-situ training that support exciting prospects of negative number multiplication. The tensor core can efficiently process 112  × 112-pixel images, potentially scaling up AI tasks and offering nanosecond latency without needing a digital processor.

The off-target effects of any CRISPR-based genome editor are identified with Tracking-seq.

Economic evaluation of utilization of digital technologies for cataract screening remains unknown. Here the authors show that digital hierarchical screening is cost-effective in China and annual screening proved to be the most cost-effective option.

A Li⁺-assisted liquid-phase reduction method is reported, which converts crystalline metal oxides into amorphous metal oxides. The electrostatic interaction between the naphthalene radical anions and Li⁺-inserted metal oxides is found to promote the amorphization process.

Recent studies have reported the exceptional plasticity of InSe van der Waals crystals, but their deformation-correlated lattice dynamics remains unexplored. Here, the authors investigate the correlations of plastic interlayer slip, lattice anharmonicity and thermal transport in β-InSe crystals via neutron scattering techniques.

Data from two large longitudinal cohorts in China, in which the participants were clustered into five groups based on their metabolic characteristics, show that a signature of microbiome age modulates the risk of cardiovascular disease in metabolically unhealthy individuals.

Ulcerative colitis is associated with increased infiltration and cellularity, yet the precise tissue topology remains poorly understood. Here the authors employ imaging mass cytometry and single-cell RNA sequencing to characterise intestinal lesions in patients with ulcerative colitis, and show the architecture at the individual cell level which includes a decrease in the resident macrophage population.

A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

Textbook theory asserts that dislocation hardening inherently sacrifices ductility. Here, the authors report that high-density dislocations with segregation-modified configurations produced by additive manufacturing increase strength without compromising ductility.

SpatialGlue is a graph neural network-based approach for integrating multimodal spatial omics data. Combining complementary data modalities improves the discovery of spatial domains as well as the identification of cell subpopulations across tissues.

Thorough evaluation of CRISPR RNA-guided nucleases off-targets in cells is required for advancing gene therapies. Here the authors report SURRO-seq for the simultaneous investigation of thousands of off-target sites for therapeutic RNA-guided nucleases in cells.

Single-cell transcriptome profiling of human aneuploid blastocysts highlights global transcriptomic alteration and identifies novel dosage-sensitive genes in aneuploidy. Aneuploid embryos undergo unstable epiblast maturation caused by defects in the TGF-β and FGF pathways that impact trophectoderm progression.

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.

The use of rigid linkers to control the relative position and interaction of donor and acceptor units in exciplex emitters leads to the realization of organic light-emitting devices with enhanced external quantum efficiency.

Ultrathin films of gallium oxide with a dielectric constant of around 30 can be formed on the surface of molybdenum disulfide using a liquid metal-based approach and used as the gate insulator in transistors.

Chromosome-level genome assemblies of three Allium crops (onion, garlic and Welsh onion) and spatial RNA sequencing provide insights into Allium trait evolution and gene expression patterns during onion bulb formation.

Intentional doping is important in semiconductors in order to tune the material property, yet the mechanism in metal halide perovskite is not well-understood. Here, the authors use silver, strontium, and cerium ions to showcase n-type doping on perovskite surface even up to metallic state.

The molecular mechanisms determining the response to radiotherapy remain incompletely understood. Here, the authors demonstrate that the E3 ubiquitin ligase and intracellular Fc receptor, TRIM21, impairs CD8⁺ T cell responses in nasopharyngeal carcinoma tumour models following ionizing radiation.

Atomically intimate assembly of FeO_x-Rh-ZrO₂ dual interfaces by selectively architecting highly dispersed FeO_x on ultrafine raft-like Rh clusters supported on tetragonal zirconia enables highly efficient tandem conversion of syngas to ethanol.

The mechanisms of intermetallic compound (IMC) formation during annealing are poorly understood. Here, the authors identify five stages of PtFe-IMC formation at the atomic level using in-situ STEM, emphasizing the role of high temperature in achieving the targeted stoichiometric ratio.

A scalable workflow involving a pMHC-displaying yeast system is introduced to identify precise virus epitope sequences and corresponding T-cell receptor (TCR) sequences from memory T cells.