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Dietary sugar intake may contribute to the development non-alcoholic fatty liver disease. Here the authors investigated the effects of chronic dietary sucrose on the liver-adipose-microbiome axis in mice, and report that sex is a moderating factor that influences sucrose-driven lipid storage in the liver and adipose tissue lipolysis.

NsrR is a bacterial transcriptional regulator that acts as a nitric oxide (NO) sensor. Here, the authors present the crystal structure of NsrR, which reveals an unusual Fe-S cluster coordination and explains how NO exposure leads to the degradation of the cluster.

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.

The authors determined a set of structures of the methylase Cfr-methylated 70S ribosome with iboxamycin and tylosin, two antibiotics that evade Cfr-mediated drug resistance, and revealed two distinct mechanisms by which small molecules can maintain their ability to engage the Cfr-methylated ribosome.

A 51-minute-orbital-period, fully eclipsing binary system consisting of a star with a comparable temperature to that of the Sun but a 100 times greater density, accreting onto a white dwarf is reported.

Premarineosin A, a potent and selective antimalarial natural product, is a promising yet underexplored scaffold due to its limited availability and synthetic complexity. Here, the authors employ metabolic engineering and late-stage functionalization to enhance the production of premarineosin A and unveil analogs with enhanced potency.

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.

In bacteria and archaea, small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci are involved in an adaptable and heritable gene silencing pathway. This pathway depends on transcription of the CRISPR loci and processing by endonucleases. Structures of Cse3-type endonuclease bound to RNAs representing the cognate pre-crRNA substrate and a mimic of the cleaved product as well as a structure of the Cse3-product complex demonstrate the basis of sequence-specific RNA recognition and suggest a catalytic mechanism for this family of endonucleases.

Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity

This study reports on excavations of hearths and stone artefacts from 20,000-year-old deposits at Dargan Shelter, which at an elevation of 1,073 m is believed to be the oldest occupied high-altitude site in Australia.

The efficiency of kesterite solar cells has been stuck at 12.6% since 2013 due to challenges in controlling defects. Now Gong et al. present a low-temperature annealing of the kesterite/CdS junction to form an epitaxial interface with a low defect density, enabling 13%-efficiency devices.

By leveraging paired microbiome and human gene expression data from pediatric patients who underwent hematopoietic cell transplantation, distinct lung–immune system–microorganism interactions were identified as important drivers of fatal lung injury.

Behavioural studies with deafened rats show that locus coeruleus activity and plasticity are key to rapid adaptation to and long-term hearing performance with cochlear implants.

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.

Here, Ye et al use high-resolution NMR in conjunction with in vitro and in vivo assays to show the catalytically important C-terminal regions of human Atg3 are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix.

The wireless and photoelectrochemical stimulation of primary rat dorsal root ganglion neurons is demonstrated by shining laser light onto coaxially doped silicon nanowires deposited on the neuronal membrane.

The antimicrobial β-lactone obafluorin is produced by a Nonribosomal Peptide Synthetase (NRPS). Here the authors present the crystal structure of the obafluorin NRPS and develop a reconstitution assay that allows them to analyse product formation from obafluorin NRPS mutants and alternate substrates.

Light-sheet microscopes are increasingly used for imaging cleared tissues, but have imposed constraints on sample geometries and protocols. Here the authors present a multi-immersion open-top light-sheet microscope to overcome these limitations and enable high-throughput imaging of samples processed with various clearing protocols.

Increased UV–optical nuclear emission in a nearby galaxy together with a spectrum showing emission lines typical of unobscured AGNs and Bowen fluorescence features suggests a longer-term event of intensified accretion onto the central supermassive black hole.

The properties of chiral conjugated molecules, such as the absorption and/or emission of circularly polarized light or electron transport, are highly anisotropic. Now it has been shown that templating layers can control the orientation and anisotropic properties of small chiral molecules in bulk thin films useful for a range of emerging technologies.

A detailed understanding of the catalytic target DNA cleavage mechanism by CRISPR–Cas9 has been lacking. Now the key modulating role of Mg²⁺ in the conformational activation of Cas9 and the influence of active site residues on the protonation state of catalytic H840 are demonstrated, ultimately unravelling the catalytic mechanism.

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.

X-ray detection of an ultrafast outflow of gas is strongly linked with energy emission from the inner accretion disk of a black hole, suggesting that X-rays ionize the outflowing disk wind.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

High resolution intravascular imaging in the brain is limited by the high tortuosity of the vasculature. Here the authors present a fiber optic imaging technology using high-frequency optical coherence tomography (HF-OCT) to provide volumetric high resolution images in the highly tortuous cerebral vasculature.

Using phenotypic screening followed by optimization of side activities, the authors here identify pyrazolopyrimidine phosphodiesterase (PDE) inhibitors as anti-cryptosporidial drug leads. Humanizing a Cryptosporidum PDE by CRISPR indicates they target the parasite enzyme.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Crotonylated lysine residues within histones are linked to transcriptional activation in a process involving histone mark ‘reader’ proteins. Crystallographic analysis of the YEATS domain of the Taf14 protein reveals a mode of crotonylated histone mark recognition via a π-sandwich motif.

Phage Thoeris anti-defence proteins Tad1 and Tad2 both achieve anti-CBASS activity by simultaneously sequestering CBASS cyclic oligonucleotides.

A wearable electrochemical patch for the real-time monitoring of the biomarker C-reactive protein in sweat detects elevated concentrations of the protein in patients with acute or chronic inflammation.

Splicing factor PTBP1 is reported to promote oncogenic functions in glioblastoma (GBM). Here the authors show splicing factor SON upregulates PTBP1 expression while supresses its paralog PTBP2 through alternative splicing and the inhibition of SON reduces GBM stemness and growth.

The atmospheric terminator region of WASP-39 b, a hot gas giant exoplanet, is inhomogeneous, despite past assumptions, with the evening terminator being hotter and thus probably clearer, and the morning terminator probably being cloudy and consequently cooler.

Highly bioactive supramolecular nanostructures displaying sulfated glycopeptides on their surfaces were designed in order to mimic the polysaccharides that bind and activate a plethora of proteins in mammalian biology during development and tissue regeneration.

A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.

A method for measuring oxygen abundances using optical and far-infrared emission lines provides absolute metallicities of the interstellar gas in Markarian 71 and could be applied across cosmic history.

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.

Mucosal-associated invariant T (MAIT) cells sense riboflavin biosynthetic intermediate antigens with a semi-invariant MR1-restricted T-cell receptor (TCR). Here the authors identify a new MR1-restricted TCR that senses cells infected with S. pyogenes, a bacteria unable to biosynthesize riboflavin.

Schizophrenia (SZ) is a severe psychiatric disorder; unfortunately, only ~1/3 of patients respond favorably to treatment. Here, the authors reveal hyperacetylation of histone H2A.Z in SZ neurons and postmortem SZ human brain tissues. They further show BRD4 is a reader of hyperacetylated H2A.Z and treatment with bromodomain inhibitor JQ1 largely rescues abnormal gene expression associated with SZ.

Iron-rich carbonate–sulfate melts are fundamental to the formation of iron oxide–apatite ore deposits, according to a detailed fluid-inclusion study that characterized the mineralizing fluids for two mineralizing systems in the United States.

The structure of GlyRα3 in complex with a selective potentiator that decreases neuropathic pain in an animal model identifies a novel allosteric regulatory mechanism.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

The mechanical microenvironment influences stem cell pluripotency. Here, the authors culture stem cells in microgels with controlled volumetric confinement and identify Plakoglobin as a mechanoresponsive regulator of pluripotency in mouse and human.

A light-sheet microscope images large surgical and biopsy specimens non-destructively over large fields of view in two and three dimensions, with the same level of detail as traditional slide-based histopathology.