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Myeloid derived suppressor cells (MDSC) use different metabolic mechanisms to adapt to the tumour microenvironment. Here the authors show that 6-phosphogluconate dehydrogenase (6PGD) is important for MSDC function and that blockade of 6PGD impaired MDSC function and suppresses tumour growth leading to metabolic and functional changes in the MDSC and a more pro-inflammatory phenotype.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Integrating computational analyses of T cell exhaustion and mitochondrial fitness atlases with in vivo CRISPR screens has identified KLHL6 as a dual-negative regulator of both exhaustion differentiation and mitochondrial dysfunction, highlighting its potential as a target to enhance anti-tumour immunity.

The R21/Matrix-M vaccine, but not the ME-TRAP vaccine, was protective against intradermal challenge with Plasmodium falciparum sporozoites, while neither was protective against direct venous inoculation, potentially explaining previously observed differences in protection.

Detection of ultracold molecules based on absorption imaging have inherent limitations. Here, the authors demonstrate spatially resolved detection of single ultracold 87Rb133Cs molecules in the bulk, extending recent microscopy developments from ultracold atoms to molecules.

Nonlocal noise thermometry enables experimental probing of energy transport in emergent states of matter and devices in low dimensions.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

TRPML2, a lysosomal TRP channel, regulates endolysosomal integrity and chemokine secretion. This work reports the cryo-EM structures of TRPML2 in multiple states bound to modulators revealing its diverse regulatory mechanisms among ion channels.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Silicon carbide is a polymorphic material with over 250 known crystal structures. Here the authors show that such polymorphism can be used as a degree of freedom for engineering optically addressable and coherently interacting spin states, including many with room-temperature quantum coherence.

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.

Subduction-driven warming and uplift are linked to the Cambrian Explosion, and Li-Os-Sr isotopes trace enhanced erosion of phosphorus-rich juvenile rocks that boosted productivity and oxygen levels to fuel animal diversification.

The explosion of alkali metals in water is a typical high-school chemistry experiment, but its mechanism is not fully understood. Using high-speed cameras and molecular simulations it is now shown that a key early step in this reaction is the migration of electrons from the alkali metal into water, leading to a charging of the metal's surface and subsequent Coulomb explosion.

A polymerization method for converting elemental sulfur into a chemically stable, processable and electrochemically active copolymer has been described. This methodology — termed inverse vulcanization — is conducted by a one-step process using liquid sulfur, as both reaction medium and reactant, and vinylic comonomers to form polymeric materials with a high content of sulfur (50–90 wt%).

RNA-binding proteins play key roles in post-transcriptional gene regulation. Here, Hemm et al. developed RAPDOR, a widely applicable tool based on Jensen-Shannon Distance and the analysis of similarities that identified 165 potential RNA-binding proteins from GradR analysis in a cyanobacterium.

Dextran sulfate sodium is a colitis inducer that stimulates a ROS–Src–IP6K2 signaling axis to generate 5-IP₇, which sterically inhibits PI(4,5)P₂ phosphatases to promote PI(4,5)P₂-mediated E-cadherin endocytosis and epithelial junction breakdown.

Membrane trafficking is essential for organelle biogenesis. Here, the authors discover an alternative assembly of the Commander trafficking complex and show its role in melanosome biogenesis and in a subtype of albinism.

The role of lactate in modulating sleep-wake architecture is unclear. Here, the authors show that downregulation of astrocytic MCT4 or orexinergic MCT2 reduces orexinergic activity and wakefulness by impairing lactate export and import, respectively, during wake events.

Graphene energy transfer with vertical nucleic acids (GETvNA) is a general approach enabling dynamical observations of DNA structural changes and DNA–protein interactions with spatial resolution down to the Ångström scale.

In the double-blind, placebo-controlled phase 2 ARGO trial, patients with active psoriatic arthritis treated with a nanobody targeting IL-17A and IL-17F showed substantially better disease response rates compared with those receiving placebo treatment.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

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).

The authors present PIONEAR–seq technology to assay in vitro binding of pioneer transcription factors to nucleosomes. The PIONEAR–seq data reveal that a nucleosome’s broader sequence context regulates the interactions of pioneer transcription factors via DNA bendability.

Recently, a reconfigurable DNA nunnery (domino array) was created with four-way DNA junction motif to realize stepwise transformation by the information relay between neighbouring four-way junction units. Here, the authors generate a DNA domino array with same sequences at every junction and use it as a platform to study how the design of DNA bases at junctions influences the kinetics and thermodynamics of transformation of four-way junctions in reconfigurable DNA nanoarrays.

Researchers identified three distinct white matter hyperintensity progression patterns, validated in both patients and healthy individuals. Each pattern links to different vascular risks and outcomes, improving stroke prediction.

Networks of miniaturized magnetoelectric wireless implantable devices can be individually powered and controlled by a single transmitter, show power and transfer data efficiencies that scale with the number of receivers and be used for spinal cord stimulation and cardiac pacing in large animals.

Genetic engineering of a yeast strain provides rare but essential pollen sterols for honeybee colonies.

Following activation, GABA_A receptors (GABA_ARs) undergo desensitization, the impact of which on inhibitory neurotransmission remains unknown. Here the authors describe an enduring form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 h following desensitization of GABA_ARs.

The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.

The ability to physically partition the human brain at a spatial resolution comparable to neuroimaging methods enabled the development of a brain-wide atlas of mitochondrial content, specialization and enzymatic oxidation and phosphorylation activities.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

Using diamond anvil cell and high temperature experiments, this work proves that the interaction between deep hydrogen rich fluids and reduced carbon minerals may be an efficient mechanism for producing abiotic hydrocarbons at the upper mantle’s pressures and temperatures.

Efficient removal of apoptotic cells by phagocytosis underlies tissue development, wound repair, host defense and organ homeostasis. Here, authors identify TRPM7 as a regulator of cargo acidification and Ca2+ signaling during apoptotic cell clearance.