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In patients with advanced clear cell renal cell carcinoma (ccRCC), sitravatinib (tyrosine kinase inhibitor) has shown efficacy both alone and in combination with nivolumab (anti-PD-1). Here, the authors investigate triplet combination of sitravatinib with nivolumab and ipilimumab (anti-CTLA4) in patients with metastatic ccRCC and longitudinal single-cell transcriptomic analysis.

Genome-wide analyses using fetal and parental genotypes identify 40 independent associations influencing placental weight and highlight the role of the fetus in preeclampsia risk and placental growth regulation via insulin signaling.

Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Zhang et al. performed a multi-regional multi-omics study, identifying brain-wide mitochondrial and synaptic defects in neurons and glial inflammation as key mechanisms underlying central nervous system impairment in COVID-19, potentially triggering neurodegeneration.

On 1–2 November 2024, the annual Biomarkers of Aging conference welcomed academic and industry scientists, and partners from governmental and nongovernmental organizations, to Harvard Medical School in Boston, USA, to discuss new insights into measuring and monitoring human aging, with the aim of clinical translation. In this Meeting Report, we summarize the conference and offer potential future directions for the Biomarkers of Aging Consortium and the longevity science community at large.

Qutrits, or quantum three-level systems, can provide advantages over qubits in certain quantum information applications, and high-fidelity single-qutrit gates have been demonstrated. Goss et al. realize high-fidelity entangling gates between two superconducting qutrits that are universal for ternary computation.

Oblique line scan microscopy achieves nanoscale spatial and sub-millisecond temporal resolution across a large field of view, enabling improved and robust single-molecule biophysical measurements and single-molecule tracking in both cells and solution.

A versatile and rapid metallaphotoredox catalytic method of making ³H- and ¹¹C-labelled tracer compounds for use in positron emission tomography (PET) is reported.

The authors here show that chromatin interactions during mouse fetal development are spatiotemporally dynamic. Integrating interactomes with other datasets predicts target genes for candidate enhancers and helps interpret noncoding risk variants in the human genome.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

Through circuit dissection in juvenile, adolescent and adult mice, Klune, Goodpaster and colleagues reveal multiple developmental switches in mPFC–NAc and mPFC–BLA pathways that underlie developmental transitions in threat avoidance behavior.

The development of materials for the effective removal of oils and solvents from water is of global importance. Here, the authors show that porous, hexagonal boron nitride nanosheets are capable of absorbing many times their own weight in oil while repelling water, and may be cleaned for reuse by heating or burning in air.

Transition metal trichalcogenides are layered materials with strong in-plane anisotropy, and their vibrational characteristics remain largely unexplored. Here, the authors present high-pressure Raman studies to uncover unusual vibrational effects within this specific class of materials.

Using a single strategy to make a number of related intermediates is a useful strategy in the total synthesis. Here, the authors report the synthesis of a number of natural products, employing two diastereomerically complementary metal-catalyzed cyclizations as the key step to access a number of frameworks.

Fast keying and mode switching exploiting the orbital angular momentum of light are sought after in optical communications and quantum key distribution for larger transmission capacity and higher security. Here Strain et al., propose a compact thermo-optically tunable vortex emitter with microsecond switching rates.

α-tubulin acetylation is an evolutionarily conserved modification but despite its prevalence, the physiological function of this process remains poorly understood. Here, the authors show that α-tubulin acetylation regulates p38 kinase signalling and expression of the anti-inflammatory cytokine IL-10 in macrophages.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

As accusations of scientific misconduct in China become rife, some fear persecution reminiscent of that used in the Cultural Revolution.

The authors collate literature on the responses of bird assemblages to forest loss and show that locations with a more variable natural environment and a longer history of agricultural land use have bird assemblages that are more tolerant to forest loss.

Paired transcriptomic and chromatin accessibility profiling are used to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, including cell types with key roles in physiological and social behaviour functions have been identified.

Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.

Loss of Kmt2c or Kmt2d in mice drives the redeployment of KMT2A–menin to bivalent promoters, leading to changes in gene expression. This primes cells for transformation and elicits sensitivity to EGFR inhibitors.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

An error detecting code running on a trapped-ion quantum computer protects expressive circuits of eight logical qubits with a high-fidelity and partially fault-tolerant implementation of a universal gate set.

Selective catalytic oxidation (SCO) of NH₃ to N₂ is a highly effective approach for reducing NH₃ emissions, though achieving high conversion across a broad temperature range without over-oxidation to NOx remains challenging. Here, the authors introduce a bi-metallic surficial Pt-Cu catalyst that effectively removes NH₃ from both stationary and mobile exhaust sources via SCO.

Methods for the anti-Markovnikov-selective hydrochlorination of unsaturated C–C bonds are limited by the need for stoichiometric reagents, highly oxidizing photocatalysts and multiple synthetic steps. Now the combination of ligand-to-metal charge transfer and hydrogen atom transfer reactivity enables the anti-Markovnikov-selective hydro- and deuterochlorination of unsaturated hydrocarbons using iron photocatalysis.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Bunyaviruses are a large group of viruses that infect a wide range of organisms, including insects, animals, plants, and single-celled organisms. Here, Terhzaz et al show that the non-structural protein NSm is required for cell-to-cell spread and egress in the mosquito midgut.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

A main challenge for the use of CAR-T in solid tumours is the identification of surface proteins as feasible targets. Here, the authors show TYRP1 as a target for CAR-T cell therapy in preclinical models of cutaneous, acral and uveal melanoma.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Maneix, Iakova and colleagues report that cyclophilin A is a chaperone for, and regulator of, intrinsically disordered proteins within haematopoietic stem and progenitor cells, with potential effects on ageing-like phenotypes and lineage commitment.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

A neural epigenetic signature detectable via plasma analyses is prognostic in patients with glioblastoma, resembling an oligodendrocyte-progenitor- and neuronal-progenitor-cell-like state and showing increased neuro-to-glioma synapse formation.

HOXA9 plays an important role in acute myeloid leukaemia (AML), but its relevance for other blood malignancies is unclear. Here, the authors show that HOXA9 has a binary switch function that can clinically stratify AML patients, and model how the interactions with JAK2, TET2 and NOTCH impact myeloproliferative neoplasms.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Controlled breaking of a chemical bond by mechanical forces can provide key insight into reaction mechanisms. Here the authors, using atomic force microscopy and computations, measure the forces involved in breaking a single dative bond between a CO molecule and a ferrous phthalocyanine complex.

Genome-scale genotyping datasets often contain missing data that negatively affects downstream analysis. Here, authors propose a genotype imputation method based on a Transformer framework that excels at imputing missing genotypes of genetic variants in various scenarios.

Tumour endothelial cell macropinocytosis is the dominant mechanism for nanoparticle entry into the tumour. Enhanced nanoparticle tumour accumulation may be due to upregulated macropinocytosis membrane ruffling compared with most healthy tissues.