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Effective target engagement of drugs relies on them achieving sufficient intracellular concentrations. Here, using a multimodal imaging pipeline the authors demonstrate that uneven distribution and uptake of PARP inhibitors in ovarian cancer patient-derived explant models correlates with therapeutic response.

Membrane-based separation methods are promising for ion extraction, though current commercial membranes have unfavorable selectivity among similar ions. Here the authors design a crown-ether based membrane for preferential separation of potassium ions in mixtures of monovalent and divalent cations.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Self-assembled hole-selective molecules can enable high performance in perovskite solar cells, but controlling the hole extraction efficiency is challenging. Tianyu Li et al. address this by designing molecules that adopt a quasi-random orientation on the substrate.

Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.

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.

An improved faba bean reference genome and resequencing of winter and spring faba bean accessions identify genetic determinants of winter hardiness.

The morphology of hole-selective contacts is key to the stability of perovskite solar cells. Feng et al. use self-assembled molecules with extended conjugation and hydroxyl groups to form dense, amorphous films that suppress degradation induced by ion migration.

N input and warming alter plant traits and mycorrhizal communities, reducing belowground C inputs and stable soil organic C while accelerating decomposition, highlighting root–mycorrhizal interactions as key regulators of soil C under global change.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

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.

Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

Self-assembled monolayers are efficient hole-selective contacts but suffer from aggregation and adhesion issues. To address these, Wang et al. introduce a dimeric molecular design that forms a hydrogen-bond network, enabling 28.4% certified efficiency in all-perovskite tandem solar cells.

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

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

Defining the spatial organization of tissues and organs like the brain from large datasets is a major challenge. Here, authors introduce CellTransformer, an AI tool that defines spatial domains in the mouse brain based on spatial transcriptomics, a technology that measures which genes are active in different parts of tissue.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Bioactivity benchmarks are key to evaluating and improving methods to predict chemicals’ specific biological activity. Here, the authors find existing benchmarks poorly suit this goal; their assays are often well-predicted simply by counting cells. They propose new guidelines and curated benchmarks.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Single-nucleus epigenomic maps of the adult human brain and spinal cord reveal that adult oligodendroglia retain developmental chromatin patterns, suggesting a molecular memory that may shape repair processes and cancer vulnerability.

Metastatic triple negative breast cancer (mTNBC) has limited treatments options. Here, this group presents a combination of low-dose cyclophosphamide, anti-CSF1R, and anti-PD-1 therapies to boost immune cell infiltration and reduce recurrence in aggressive TNBC models.

The inter-system crossing induced by selenium may undesirably enhance formation of triplet excitons in non-fullerene acceptors, leading to increased non-radiative losses. Here, the authors introduce achiral N-alkyl substituents, achieving maximum efficiency of 20.4% for ternary organic solar cells.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Chen et al. report a tailored self-assembled monolayer to create a localized 2D/3D perovskite heterojunction. This strategy reduces interfacial loss, achieving photovoltages >90% of thermodynamic limit for wide-bandgap cells, and enables perovskite-organic tandem solar cells with efficiency of 27.11%.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Jia et al. compared the performance of 4 counterfactual screening strategies: co-testing, HPV primary with liquid-based cytology (LBC) triage, HPV-only, and LBC-only. They show that LBC-only detects fewer CIN2+ cases yet still increased referrals while HPV-only reduces referrals but had a lower CIN2+ detection rate.

This scoping review examines previous experience in performing silent evaluations of clinical AI applications, collecting evidence from 75 studies on implementation features and the sociotechnical context.

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.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

This study presents a programmable mRNA nanomedicine that induces tumour-specific immunogenic cell death in immunologically cold and metastatic tumours with enhanced safety, advancing next-generation strategies for personalized cancer immunotherapy

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Employing intrusions with varying SiO₂ to represent the different layers of the continental crust (CC), a bulk CC δ^98/95Mo of −0.116 ± 0.011‰ is established, pointing to long-term mass balance between crustal growth and destruction.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Tuning surface charge and polymer length enables PEG-grafted nanoparticles to assemble into cubic superlattices resembling ZnS, NaCl, CsCl, simple cubic and diamond, offering a programmable route to valence-free crystals.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Selecting foxes for tameness reshapes their gut microbes. Tame foxes lack bacteria linked to fear and aggression and show microbial pathways tied to brain chemistry, suggesting gut microbes may help drive behavioral change during early domestication.

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.

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.

MATTERIX, a multiscale graphics processing unit-accelerated framework for high-fidelity digital twins and workflows of chemistry laboratories, is presented, simulating robot and device operation, fluids and powders, and processes such as heat transfer and chemical kinetics.

Examining human brain organoids and ex vivo neonatal murine cortical slices demonstrates that structured neuronal sequences emerge independently of sensory input, highlighting the potential of brain organoids as a model for neuronal circuit assembly.

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.

Efficient and durable energy storage is vital for renewable integration. Here, the authors design an aqueous iron-cerium redox flow battery using a universal complexing agent that enhances stability and efficiency, achieving long cycle life and high performance in neutral conditions.