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Obesity, a surging global health challenge, needs effective and innovative therapeutic models. Here, the authors show in mice a microneedle drug delivery platform loaded with metal-organic frameworks (MOFs) and CRISPRa-UCP1 system to enable sono-gene therapy for obesity.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

Direct air capture (DAC) technologies to remove CO₂ from the atmosphere are widely used in climate policy scenarios, but their real-world impacts are not well understood. A life-cycle assessment by Madhu et al. compares two main DAC approaches and quantifies their environmental impact and resource needs.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

Using molecular dynamics simulations and functional assays, authors track the structural changes in heterotrimeric G proteins in response to receptor coupling that lead to the ejection of GDP, the rate-limiting step during G-protein activation.

Understanding the chemistry of perovskite precursor solutions enables improved film optoelectronic properties, allowing the fabrication of multijunction solar cells achieving power conversion efficiencies beyond the radiative limit of single-junction cells.

This study introduces a system called TArgeted Cohesin Loader (TACL) that recruits cohesin complexes at defined genomic regions and induces loop extrusion events in living cells, exploring its impact on chromatin organization and gene expression.

Here the authors identify RNA G-quadruplexes as temperature-sensitive regulators of alternative splicing and gene expression, opening potential therapeutic avenues such as neuroprotection with potassium channel blockers.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Here, the authors fabricate a metasurface with nanometre-sized plasmonic hotspots that interact coherently with WS₂ excitons, achieving ultrastrong exciton-plasmon coupling.

Desmocollin 2 (DSC2) binds to the EBV glycoprotein H/glycoprotein L complex and allows for virus entry to epithelial cells, which could be blocked by DSC2-specific antibodies. DSC2 allowed for virus entry independent of Ephrin receptor A2.

DNA methylation analysis identifies a MYCN-driven subgroup of aggressive retinoblastoma that may benefit from MYCN-targeted therapy.

The AcP10 protein—an active uridine kinase, encoded by the beluga whale coronavirus SW1—is an antagonist of the integrated stress response that acts downstream of phosphorylation of the translation initiation factor eIF2, irrespective of which eIF2 kinase is activated. AcP10 acts as a competitive inhibitor of the eIF2[P]–eIF2B interaction by binding to eIF2B. A protein with a similar function is also encoded by Aichivirus, a picornavirus.

Solid-state lithium-sulfur batteries promise high energy density, long-term performance, and enhanced safety, but face challenges with interfacial issues due to poor solid–solid contact. Here, the authors review the benefits and challenges of in situ polymerization, discussing its potential to enhance electrode-electrolyte integration and improve battery performance, and proposing future prospects for multifunctional polymer solid-state electrolytes.

Fc–IL-4, a typical type 2 cytokine, reinvigorates exhausted CD8⁺ T cells in tumours, underscoring this fusion protein as a potent immunotherapy that synergizes effectively with type 1 immunity against cancer.

A newly identified coronavirus isolated from farmed minks can use the receptor ACE2 to infect cells of different mammalian species, including human cells, which has implications for potential zoonotic spillover events.

Single-stranded DNA donors using current design parameters remain inefficient for precise gene editing. Here, the authors engineer RAD51-preferred sequences into HDR-boosting modules for donors, enhancing HDR efficiency across various genomic loci and cell types.

Alkhoury et al. show that the class 3 phosphatidylinositol-3-kinase Vps15 subunit coactivates the circadian clock transcription factor Bmal1–Clock for metabolic rhythmicity in the liver and promotes pro-anabolic de novo purine synthesis.

It is believed that human Influenza HA glycoprotein attaches to alpha2-6 linked sialic acids (SA) on cells, while avian viruses bind to alpha2-3 linked sialic acids, therewith contributing to host tropism. Here, Liu et al. show that mixing low-affinity alpha2-3 SA with low amounts of high-affinity alpha2-6 SA increases binding and entry of human viruses and the converse for avian virus. This shows that receptor recognition is not as strict as currently assumed and provides evidence that heteromultivalent interactions between human/avian HA and SA contributes to host adaptation.

Genetic and pharmacological inhibition of the overproduction of oxalate in the liver alleviates metabolic dysfunction-associated steatohepatitis in male mice.

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, the authors report that citronellal stimulates skin renewal by promoting keratinocyte proliferation through the activation of TRPV3. Structural and functional analysis elucidate that essential oil ligands activate TRPV3 channels by competitively displacing endogenous lipids from the vanilloid site. These findings can help move skin healthcare forward.

Using globally consistent measurements and high-resolution modelling, this study finds that black carbon emissions are generally underestimated in the Global South.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

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.

Here, the authors report the engineering, structural and biological characterization of synthetic nanobodies (sybodies) that display potent therapeutic activity against SARS-CoV-2 infection in animal models via targeting the virus receptor-binding domain.

Binding modes of antigenically drifted hemagglutinins of human influenza A viruses have been determined by NMR using synthetic N-glycans having ¹³C-labeled monosaccharides to pinpoint which monosaccharides of extended LacNAc chains engage with the HAs.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Samples of serum from individuals immunized with the BNT162b2 vaccine show neutralization activity against engineered SARS-CoV-2s bearing the spike mutations from B.1.617 and other variants.

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.

Immunotherapy has improved patient outcomes in those with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) but less so in the neoadjuvant setting. Here, the authors report the efficacy, safety and exploratory biomarker analysis of a phase II clinical trial investigating neoadjuvant tislelizumab (anti-PD-1) and afatinib (EGFR TKI) in patients with locally advanced HNSCC.

Ruscetti and colleagues show that the pancreatic cancer tumor microenvironment suppresses immune surveillance following therapy-induced senescence via repression of inflammatory gene expression through EZH2.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

SUMO modification regulates protein function, with SENP enzymes controlling SUMO removal. Here, the authors present crystal structures of SENP5 bound to SUMO1 and SUMO2, revealing how structural features drive its preference for SUMO2 and offering insights into SUMOylation regulation.

Genetically encoded sensors have been developed and become versatile tools for imaging serotonin dynamics. Here, authors developed a family of serotonin (5-HT) sensors (sDarken), three variants with different affinities for 5-HT enable high spatiotemporal resolution of 5-HT dynamics.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.