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Cyclohexanone oxime electrosynthesis has low Faradaic efficiency at high current densities. Now, high NO coverage is found to favour oxime production. A doping strategy is proposed to break the electronic symmetry of catalytic sites, achieving ampere-level electrosynthesis with 86% Faradaic efficiency by suppressing NO–NO coupling at high NO coverages.

The relationship between interacting sites and catalytic mechanisms in single-atom catalysts remains unclear. Here a support engineering strategy is used to tune the binding strength between single-metal atoms and the support, optimizing active Cu sites and enhancing CH₄ formation.

Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signalling remains unclear. Here the authors show that PD-1 function is reduced when mechanical support on ligand is removed.

Banerjee et al. report that the Vps13-like lipid transport protein BLTP2 regulates plasma membrane fluidity by maintaining phosphatidylethanolamine homeostasis. BLTP2 also facilitates breast cancer cell growth, suggesting a separate role in tumorigenesis.

Understanding the role of atomic sites in photocatalytic CO₂ reduction remains challenging. This study provides insights into dynamic Ru^δ+-O/Ru⁰-O pair reconstruction and explores approaches to enhancing intermediate regulation and asymmetric *CO-*CHO coupling for producing C₂₊ products.

The anti-tumour effect of immune checkpoint inhibitors is potentiated by CD137 agonists in preclinical models, but translation of these results to the clinical practice is hampered by toxicity. Authors describe here a human CD137xPD-L1 bispecific antibody with improved anti-cancer activity whilst maintaining low toxicity in non-human primates.

Abnormal accumulation of intra- and extracellular free nucleic acids contributes to the chronic inflammation driving intervertebral disc degeneration (IVDD). Here, the authors report a nanovesicle system to inhibit mitochondrial DNA release in nucleus pulposus cells and remove extracellular DNA from the disc microenvironment to block inflammation for treatment of IVDD.

Hydrogen sulfide (H₂S) is an important endogenous gasotransmitter, but the bioorthogonal H₂S donors are limited. Here, the authors design and synthesize sydnthiones, and investigate their bioorthogonal reactions with strained alkynes for mitochondria-targeted H₂S release.

Li, Cheng, Yu and colleagues have discovered a Cas13j family, including the compact and highly efficient LepCas13j (529 aa) and ChiCas13j (424 aa), with promising applications in RNA editing in vivo.

The protein PR1 is crucial for plant immunity but has unclear bioactivity. Here PR1 is shown to release a phytocytokine CAPE and trigger systemic acquired resistance (SAR) via a caspase-like enzyme specific for CAPE production (ESCAPE).

Electrocatalytic CO₂ reduction into multicarbon products offers a means to close the anthropogenic carbon cycle using renewable electricity. Here, the authors report a cascade AgCu single-atom and nanoparticle electrocatalyst with favorable properties to improve the selectivity of multicarbon products.

Constructing polymer-based mimics on the surface of cells has potential to manipulate cell behavior, but precise control of grafting sites is challenging. Here, the authors report a method for site selected radical polymerization on cell surfaces by metabolic labelling.

Efficient CO₂ electroreduction to C₂₊ products at high current densities remains a significant challenge. Here, the authors develop inherently hydrophobic and hierarchically porous Cu supraparticles with enhanced mass transfer and abundant C-C coupling sites for ampere-level CO₂-to-C₂₊ synthesis.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a drug target for inflammatory bowel disease (IBD), impacting immune cell movement, but current treatments carry immunosuppression risks. Here, the authors show that a Gi-biased S1PR1 agonist, SAR247799, protects the endothelial barrier in IBD models without affecting immune cell egress, offering a potential new treatment strategy.

SUMOylation plays a key role in modulating protein function. Here, the authors uncover a form of SUMOylation, termed N-αSUMOylation, where SUMO1 attaches to the N-terminus of cofilin1. This SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization.

G Protein-Coupled Receptors (GPCRs) can adopt different conformations, each linked to distinct cellular outcomes. Here the authors show that compound 17b, a novel agonist of the GPCR family member FPR, robustly activates cardioprotective but not detrimental FPR signalling, showing beneficial therapeutic effect in a mouse model of cardiac infarction.

Veniant et al. report here on a GIPR antagonist conjugated to GLP-1 analogues that reduces body weight and improves metabolic markers in preclinical and phase 1 clinical settings.

Water plays a key role in electrocatalytic CO₂ reduction, but the role of catalyst in water management is unknown. Here, the authors report the importance of catalyst in determining the function of water and demonstrate that the catalyst containing Cu⁺ promotes water activation and C₂₊ formation.

SUMOylation is a post translational modification. Here the authors show that TRPV1, which conveys thermal nociception, is SUMOylated in DRGs in inflammatory conditions and contributes to pain behavior in mice.

Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.

Click-ExM uses click-chemistry-based labeling to increase the versatility of expansion microscopy. Click-ExM enables imaging of numerous classes of biomolecules including lipids, glycans, proteins, DNA, RNA and small molecules.

A cancer vaccine is delivered to the lung by an engineered attenuated influenza virus.

Here, Li et al. develop a human liver organoid model to elucidate Dengue virus infection dynamics and identify oxyresveratrol as a potential antiviral candidate, highlighting the NRF2 pathway’s crucial role in mitigating mitochondrial damage and enhancing cellular resistance.

Characterisation of the human antibody response to SARS-CoV-2 can help the design of serological tests and vaccines. Here, the authors identify two linear epitopes in SARS-CoV-2 spike protein that elicit neutralising antibodies in several patients and could thus be useful for serology and vaccine development.

An organic regulator that can tune the crystallization sequence of active layer components has been described, achieving a certified efficiency of over 20% in single-junction organic solar cells, demonstrating remarkable tolerance for active layer thickness of 100–400 nm.

Metal-organic frameworks are promising catalysts for CO₂ electroreduction, yet limited by their poor conductivity and stability. Here, Au nanoneedles are inserted into the metalloporphyrin framework to activate C-C coupling and stabilize the structure for much enhanced ethylene production.

Electrocatalytic reduction of CO₂ into multicarbon (C₂₊) products is a highly attractive route for CO₂ utilization. Now, a fluorine-modified copper catalyst is shown to achieve current densities of 1.6 A cm⁻² with a C₂₊ Faradaic efficiency of 80% for electrocatalytic CO₂ reduction in a flow cell.

Here the authors develop a ferritin-based protein nanoparticle vaccine candidate for SARS-CoV-2, and show induction of neutralizing antibodies to variants of concern, including Omicron BQ.1, in non-human primates after initial immunization and a booster dose.

The emergence of resistant subpopulations often underlies the development of resistance to cancer therapy. Here, using a DNA barcoding approach, the authors demonstrate EGFR TKI treatment in non-small cell lung cancer enriches for resistant subpopulation which can be prevented by treatment with the multikinase inhibitor sorafenib via inhibition of MKNK, STAT3 and MCL1.

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.

The characteristics of the pores are vital for controlling the performance of covalent organic frameworks, but obtaining different chemical environments in different pores is challenging. Here, the authors report the development of covalent organic frameworks with differing pore environments.

Zhou et al. developed a specific small-molecule inhibitor of astrocytic Kir4.1 channels, Lys05, which exerts rapid-onset antidepressant effects in rodents without unwanted side effects, indicating Kir4.1 as a promising drug target.

In this study, the authors report the development of an inhalable IgM-like ACE2 and show that it broadly neutralizes SARS-CoV-2 variants, lowers viral loads and lung pathology in hamsters when administered early, and has good safety profiles in rats and monkeys.

While the STING-type-I interferon pathway plays a key role in anti-tumour immunity, current direct STING agonists have limited therapeutic benefit. Here, the authors identify ENPP1 as a safer and more effective STING-modulating target than direct STING agonism, and use an AI-based drug design platform to design the ENPP1-selective inhibitor ISM5939.

The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules.

Granzyme B is found in activated T cells and can be used as a marker of T cell activation. Here, the authors generate a fluorescent probe that can detect Granzyme B levels in tumours, and has the potential to be used as a biomarker of response to immunotherapy.

Polymers represent promising gene vectors due to their high efficiency and low cytotoxicity. Here, the authors show that fluorination increases gene transfection efficacy, while reducing cytotoxicity, and suggest an important role for this strategy in the design of efficient gene vectors.

Maintenance of proper membrane excitability is vital to neuronal function and in several neuronal types this relies on a balance between receptor-mediated excitation and inhibition. Here the authors report a crosstalk between excitatory kainate receptors and inhibitory glycine receptors that relies on the SUMOylation status of PKC.

The active sites over oxide-derived copper (OD-Cu) catalysts for CO₂ electroreduction are unclear. Here, the authors show atom-level product-specific active sites on OD-Cu surface models, where planar and convex square sites are responsible for ethylene while the step square site favours alcohols generation.

CAD, a de novo pyrimidine synthesis pathway enzyme, is known to promote chemotherapy resistance. Here, the authors shed light into this mechanism of chemoresistance, showing that chemotherapeutic drugs can promote the degradation of CAD following cleavage by activated caspase-3 on its Asp1371 residue.

Fine tuning of mechanical properties in elastomers is important for application of elastomers in flexible devices and biomedical field. Here, the authors prepare a nacre inspired PDMS-montmorrillonite composite with good mechanical properties and demonstrate crack tracing using aggregation-induced emission luminogens.