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Compact Un1Cas12f1 enzyme suits AAV delivery but is limited by narrow PAMs and modest activity. Here, authors engineer evoCas12f to recognize broader NTNR/NYTR PAMs and boost editing efficiency up to 91%, enabling efficient multiplex editing, base editing, and gene activation in cells and mice.

Allogeneic stem cell transplantation (alloHSCT) is approved for the treatment of transfusion-dependent thalassemia but remains limited to the use of matched sibling donors. In this multi-centre, phase-4 prospective clinical trial, the authors evaluate the use of alloHSCT with matched unrelated donors and haploidentical relatives.

The underlying regulatory mechanisms of of human cortical diversity remains poorly understood. Here, authors profiled human brain cells to study how they use different gene programs across cortical regions, revealing molecular rules and specific transcription factors that drive functional specialization of neurons in the brain

The role of disorder in high-entropy oxides in electrocatalysis and zinc–air batteries remain unclear. Here, the authors induce controlled multilevel structural, electronic and atomic disorder to create new active sites, enabling robust, balanced oxygen catalysis and efficient zinc–air batteries.

Most patients with B-cell leukemia respond to chimeric antigen receptor T cell (CAR T) therapy, yet many relapse due to loss of CAR T function. Here, the authors show that the metabolism of CAR T from short- and long-term responders is different, which may explain why CAR T lose functionality.

Chimeric antigen receptor (CAR)-T cell therapy has shown promise but remains limited against solid tumors. This study reports that DKK1-A2 CAR-T cells selectively target HLA-A2- and DKK1-positive tumors, suggesting their therapeutic potential in treating human cancers.

Dysregulation of H3K4 methylation is associated with neurodevelopmental disorders. Here, the authors perturb H3K4 methylation in the MGE and hypothalamus, resulting in altered gene expression and cell fate as well as changes in behavior that mimic NDD symptoms.

Riboswitches are RNA elements that regulate gene expression through dynamic changes in secondary structure. Here, the authors reveal how the glycine tandem riboswitch integrates sequential signals via stepwise folding and binding of ligands to orchestrate gene regulation during transcription.

Sex dimorphism in the incidence and mortality of hepatocellular carcinoma (HCC) has been reported. Here the authors show that, in males, androgen promotes regulatory T cell recruitment to impair γδ T cell antitumor immunity, implying that a Treg/S100a4/γδ T cell axis controls sex differences in hepatocarcinogenesis.

Using plasma proteome profiles from over 53,000 UK Biobank participants, Zhang et al. examined proteins associated with suicidal behavior and investigated pathways that could explain the association

Many vascular‑disease risk loci lack defined causal genes. Here, the authors integrate functional genomics and CRISPR screens to identify genes influencing smooth muscle cell behaviour, validating roles for FES, BCAR1, CARF and SMARCA4, with Fes loss promoting atherosclerosis and hypertension.

Autopsy brain studies can be distorted because time and temperature alter gene expression. Here, the authors show that neurons, then oligodendrocytes, sequentially activate artifact genes, and provide a tool to measure these effects in RNA sequencing data.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Here researchers reveal a microexon in the Ank3 gene encoding Ankyrin G allows cortical interneurons to fine-tune calcium signaling and firing, revealing the contribution of alternative splicing to the functional diversity among different types of neurons.

In vivo base editing of a causative mutation that leads to the neurodevelopmental disorder Snijders Blok–Campeau syndrome restores protein dosage and ameliorates molecular and behavioural deficits in a humanized mouse model of the condition.

Direct air capture (DAC) removes CO₂ from the atmosphere but remains energy-intensive at scale. Here, the authors integrate catalytic solvent regeneration and hybrid solvents with low-temperature membrane vacuum regeneration, significantly improving the energy efficiency and sustainability of liquid-based DAC systems.

In this study, the authors designed potent Enterovirus D68 capsid inhibitors that block viral binding and show that the lead compounds reduce virus levels, prevent paralysis and improve survival in EV-D68-challenged mice, even when treatment starts days after infection.

The mechanical microenvironment for MSCs is crucial for osteogenesis. Here, the authors developed a hydrogel in which MSC-secreted ALP actively remodels the surrounding heterogeneous mechanical microenvironment to promote osteogenesis for bone regeneration.

DeepRare—a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating specialized tools and up-to-date knowledge sources—has the potential to reduce healthcare disparities in rare disease diagnosis.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

The authors demonstrate that targeted protein degradation of the dengue virus capsid suppresses infection through capsid-dependent pathways rather than classical inhibition, revealing a new antiviral strategy effective against resistant viral variants.

Mass spectrometry (MS)-based proteomics is increasingly central to systems biology. Here, the authors present a high-throughput, multi-organ workflow that profiles 11,472 proteins in 507 mouse samples, enabling rapid, system-level evaluation of drug efficacy and toxicity.

In this study, authors reveal an evolutionary strategy in bacteria, where multidrug resistance are stably maintained through multicopy heterogeneous genes on a single plasmid, conferring an adaptive advantage under fluctuating clinical drug pressures.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Negative regulation of the cGAS-STING pathway is crucial to limit damaging inflammation. Here, by combining in vitro experiments and myeloid cell-specific conditional knockout mice, the authors identify the autophagy receptor TAX1BP1 as a negative regulator of STING by targeting it for degradation through Golgiphagy and ESCRT-mediated microautophagy.

In this study, the authors show that chandelier cells in the medial prefrontal cortex integrate circuit inputs, encode stimulus salience across sensory modalities, and thus influence associative learning in male mice.

Cell-free DNA is widely used in clinical testing, but its genetic basis remains unclear. Here, the authors perform cfGWAS in 28,016 pregnant women, identifying 15 loci linked to cfDNA end motifs and confirming roles for neutrophils through validation studies.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

HCMV’s pathogenic mechanism in liver disease is unclear. Using cholangiocyte organoids, this study shows infection induces TGF-β-mediated EMT, causing functional impairment and potentially link the virus to the development of bile duct pathology.

Interfacial water is of crucial importance in biology and engineering. Here, the authors identify structural transitions of interfacial water at graphite surfaces under varying electric fields and environmental conditions.

Testi and colleagues introduce an enhanced Brillouin Microscope for user-independent and high-precision mechanical measurements. Using this approach, the authors obtained insight into the biophysical properties of protein condensates involved in severe neurodegenerative diseases.

The herpes simplex virus lytic-latent balance is incompletely understood. In this study, the authors show that it is controlled by the relative abundance of host activating and repressive forkhead box (FOX) transcription factors that recruit epigenetic cofactors to the viral genome to remodel viral chromatin.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

Bacterial phosphate transporter PstSCAB is essential for survival and virulence. Here, authors reveal cryo-EM structures of PstSCAB in multiple states, uncovering how conformational changes drive phosphate import and providing insights for antibiotic development.

Nanochannel-confined polymerization enables polymer curing inside nanometre-scale two-dimensional channels. This strategy produces selective, mechanically robust, densely packed membranes and reveals how nanoconfinement reshapes polymer structure and membrane transport pathways, opening a general route to engineer functional materials by controlling chemistry in nanoscale pores.

Enhancing the carrier mobility of graphene can enable the investigation of its fundamental properties and promote device applications. Here, the authors report the fabrication of double-layer graphene devices with a quantum mobility up to 10⁷ cm²V⁻¹s⁻¹ and integer quantum Hall features at magnetic fields as low as 0.002 T.

Persistent synthesis challenges constrain the stabilization of single-atom lanthanide catalysts across many substrates. Using a method based on molten-nitrite chemistry, the atomic dispersion of lanthanide atoms on diverse substrates is achieved and exemplified by Dy₁/Pt for acidic hydrogen evolution.

Two-dimensional perovskite phases at the bottom interfaces of solar cells improve performance, but their formation is challenging. To address this, Zhao et al. graft the 2D perovskite-phase precursor onto a functionalized SnO₂ electrode substrate.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Quantum range finding struggles in bright background and at long distance. Here, the authors demonstrate a quantum-inspired, energy-time correlated classical rangefinder. It preserves quantum noise suppression, works at low power, and enables robust daylight remote ranging in real-world environments

Here the authors developed a ROS-responsive nanosystem that scavenges ROS and spatiotemporally releases anti-TIMP-1 antibodies and mesenchymal stem cell-derived exosomes, driving collagen degradation and tissue repair, and achieving strong anti-fibrotic effects with a single dose.