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Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

A combination of engineering approaches is used to improve the function of IscB for a variety of editing activities in vivo.

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.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Engineered pyroptotic vesicles formed during tumour cell pyroptosis and engineered as personalized tumour vaccines can activate a robust antitumour immune response for post-surgical tumour recurrence inhibition.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Following progression on HER2-targeted first-line regimens, there are limited HER2-targeted therapies that have demonstrated efficacy in patients with gastroesophageal adenocarcinoma (GEA). Here, the authors report the results of a phase 1 clinical trial investigating zanidatamab (a HER2-targeted bispecific antibody) in heavily pre-treated patients with advanced or metastatic, HER2-expressing GEA.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Studies on the essentiality of Ku in human cells reveal that Ku interacts with diverse double-stranded RNA molecules, including antisense Alu, and enables tolerance of Alu sequence expansion in primates.

DNA hydroxymethylation (5hmC) is typically altered in age-related diseases. Here, the authors show that 5hmC accumulates in gene bodies, partially due to prolonged quiescence, and restricts the magnitude of transcriptional changes with age.

A millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism is developed for general applications in electrotherapy and specific uses in temporary cardiac pacing.

On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.

PENSIEVE-AI is a drawing-based, digital cognitive test that can be self-administered in <5 min. It matches traditional tests in detecting cognitive impairment and dementia, offering promise for early detection in literacy-diverse populations.

Harmonic measurements have been used extensively in ferromagnetic/heavy metal heterostructures to characterize the magnetization dynamic; however, it has remained unclear about whether such techniques could be applied to antiferromagnetic devices. Here, Cheng et al demonstrate such a harmonic measurement approach in an antiferromagnet.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Spread of SARS-CoV-2 in the early phase of the pandemic has been driven by high population susceptibility, but virus sensitivity to climate may play a role in future outbreaks. Here, the authors simulate SARS-CoV-2 dynamics in winter assuming climate dependence is similar to an endemic coronavirus strain.

Targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease but is challenging. Here, the authors develop an mRNA delivery platform to treat acute lung injury in mice and demonstrate that it can reach the lower regions of the lung.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

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.

The posterolateral cortical amygdala and other connected brain regions have a key role in mediating the transition from investigative to aggressive behaviour in male mice.

Climate change is likely to impact the circulation of many infectious diseases. Here, the authors characterize the impact of climatic and demographic factors on enterovirus disease transmission and project how changes in climate may impact future transmission.

The effectiveness of community-based land protection compared to traditional top-down protection is debated. Here, the authors show that both community-managed forests and traditional protected areas in Madagascar experienced deforestation during a political crisis but the former were especially vulnerable in the post-crisis period.

The spin crossover films provide an efficient control of material properties by light excitation. In this work, the authors reveal sequential photo-switching dynamics, from local molecular rearrangement to global lattice deformation.

A multinational randomized trial shows that task-sharing via nonspecialist providers and the use of telemedicine platforms, delivery models that can overcome barriers to scalability and access, are noninferior to specialists and in-person models for treating perinatal depression.

An optogenetic tool called Opto-OGT has been developed that enables researchers to probe pathways involving modifications with O-linked β-N-acetylglucosamine (O-GlcNAc) such as OGT, mTOR and AMPK signaling with high spatiotemporal precision. The method is based on fusing a photosensitive cryptochrome protein to an O-GlcNAc transferase and enables OGT to be reversibly activated with blue light.

Recent years have seen an increasing shift from centralized laboratory diagnostics to decentralized point-of-care testing, a shift which has the potential to increase health equity. Here the authors provide their perspective on how the integration of machine learning and artificial intelligence with point-of-care technologies can - and could - support this transition

Analyses of death records over the two decades in the United States reported greater mortality from infectious and parasitic diseases, injuries and respiratory and cardiovascular diseases associated with exposures to flooding events, particularly floods caused by tropical cyclones and heavy rain.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

Adoptive T-cell immunotherapy offers promise to patients who are resistant to standard anti-viral strategies. Here the authors describe clinical observations in patients with viral complications treated with adoptive immunotherapy over the last 15 years.

A study describes an approach using designed building blocks that are far more regular in geometry than natural proteins to construct modular multicomponent protein assemblies.

Stéphane Coen and Miro Erkintalo from the University of Auckland in New Zealand talk to Nature Photonics about their surprising findings regarding a weak long-range interaction they serendipitously stumbled upon while researching temporal cavity solitons.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Here we describe an open collaborative effort termed the ‘Ruminant T2T Consortium’. It aims to generate complete diploid assemblies for many species of ruminants to examine chromosomal evolution in the context of natural selection and domestication.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

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.