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The hetero-Diels–Alder reaction is a powerful strategy for constructing six-membered heterocycles, yet natural enzymatic hetero-Diels–Alder reactions are limited to a single heteroatom. Now a bifunctional enzyme, Abx₍₋₎F, is found to catalyse the dehydration and a dual-oxa Diels–Alder reaction to form the oxygen-bridged tricyclic acetal of (−)-anthrabenzoxocinones.

Personalized nanovaccines can elicit robust T-cell response but identifying tumour-specific antigens sometimes remains challenging. Here these groups identify IFN-γ as a potent stimulator for the antigen presentation across a broad range of cancer cell types and then fabricating corresponding nanovaccine inducing poly-neoepitopic T-cell responses at low dosage.

Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.

Lfy1 is a maize mutant identified 50 years ago with increased leaf number above the primary ear and later flowering time. Here, the authors reveal that a Copia LTR-retrotransposon insertion leads to enhanced expression of an AAA ATPase encoding gene to give the mutant phenotype.

Developing a sustainable manufacturing method using biomass-derived feedstock at ambient conditions is highly desirable. Here the authors report electrooxidation route for synthesis of formamide from methanol and ammonia in water

The exact mechanism for superconductivity in iron-based superconductors remains elusive, but is thought to involve complex interactions between many orbitals. Using angle-resolved photoelectron spectroscopy, Liuet al. report the electronic structure of the single-layer parent compound FeSe.

An avian influenza H7N9 virus causes severe human disease, including acute and often lethal respiratory failure. Here, the authors report that plasma levels of angiotensin II, a regulatory peptide of the renin–angiotensin system, are associated with disease severity and fatal outcome in infected patients.

Genetic mutations are found in only 15% of sporadic ALS. Here, authors identify PCDHA9 as a candidate ALS gene and elucidate detailed underlying pathogenesis using mice with Pcdhα9 mutations that develop typical ALS phenotype and hallmark pathology.

It has been shown that targeting receptor-interacting protein kinase 1 (RIPK1) can improve response to immune checkpoint inhibitors. Here, using PROTAC technology, the authors report the design and characterization of a RIPK1 degrader, enhancing anti-tumor immunity in preclinical cancer models.

Here, combining X-ray crystallography, cryo-electron tomography and animal studies, the authors show that the monoclonal antibody against Ebola virus glycoprotein (GP1,2) 3A6 exerts protection via binds to a conformation of GP1,2 that is lifted from the virion membrane, providing insights into the mechanism of action with implications for the design of anti-Ebola therapeutics.

Convergence of heavy or light chains in antibodies recognising pathogens could drive mutations in these pathogens. Here the authors examine antibodies against SARS-CoV-2 and find that a conserved VL6-57 light chain recognising a conserved motif in the spike protein is associated with virus mutations and could drive changes in SARS-CoV-2 omicron variants.

Mina53 is identified as the enzyme responsible for removing histone 4 arginine 3 asymmetric dimethylation and is important to regulate gene expressions critical for neural stem/progenitor cell proliferation.

The independently evolved extreme holoparasites Balanophora and Sapria display convergent characteristics of genome modifications, including gene loss in particular pathways, reduction of multigene families and relaxed selection pressures.

The authors develop a general method that combines machine learning and physics to construct macroscopic dynamics directly from microscopic observations, leading to an intuitive understanding of polymer stretching in elongational flow.

In this study, authors identified neutralizing antibodies by isolating B cells from SARS-CoV-2 Delta infected patients and detect altered structural features, likely introduced by somatic hypermutation, that are involved in epitope binding and increase neutralization breadth against virus variants.

Syt7-dependent pancreatic insulin release is shown to be mediated by 5-IP₇ in response to parasympathetic stimulation of the GPCR M3R.

In this study the authors present the Thogoto virus polymerase cryo-EM structures and reveal unique RNA synthesis mechanisms among orthomyxoviruses. RNA synthesis by Thogoto virus polymerase is shown to be weakly dependent on the host factors ANP32A/B/E in human cells in contrast to influenza viruses.

The evolution of density-wave-like orders under pressure is crucial for unraveling the mechanism of superconductivity in La₃Ni₂O₇. Here, the authors provide evidence that the spin density wave is suppressed when the superconductivity emerges, and that another density wave appears above 29 GPa.

Structures of the assembled matrix protein 1 of influenza A virus in intact virus particles and of oligomers of this protein reconstituted in vitro reveal mechanisms of assembly and disassembly of influenza virus.

The neurotoxicity of organophosphate compounds damages nerve system by inhibiting acetylcholinesterase (AChE) expression, but it is difficult to overcome the deactivation of AChE. Here, the authors report the design of Lewis acid sites in metal-organic frameworks as AChE mimics for effective neuroprotection.

Chondrocyte senescence is known to play a role in the occurrence and progression of osteoarthritis. Here, the authors demonstrate that 10-hydroxy-2-decenoic acid (10-HDA), a small molecule derived from the food nutrient royal jelly, can prevent osteoarthritis by delaying chondrocyte senescence through targeting aspartyl β-hydroxylase.

Reactive oxygen species (ROS) damage cell components, necessitating their clearance through autophagy. Here, the authors show that ROS can induce autophagy by triggering TRPML1 to release Ca²⁺from the lysosomal lumen, in turn activating the autophagy and lysosomal biogenesis regulator TFEB.

Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.

Host defense against helminth infection is mediated by mucosal type 2 immunity. Using gain- and loss-of-function mouse models, and mouse intestinal organoids, Xiong et al. show that SIRT6 modulates tuft and goblet cell expansion in intestinal epithelium by activating STAT6 to maintain type 2 mucosal immunity in response to helminth infection.

Immunosuppression as a result of severe infection impairs pathogen clearance and can increase susceptibility to secondary infection. Here, the authors dissect how T cell aging and the thymic involution that occurs during this process contribute to immunosuppression and find a key role for IL-33.

CO₂ is a problematic greenhouse gas, although its conversion to alternative fuels represents a promising approach to limit its long-term effects. Here, the authors demonstrate that CO₂ can be reduced to methanol through pyroelectric catalysis under temperature variation near room temperature.

Bivalve molluscs have evolved various characteristics to adapt to benthic filter-feeding. Here, Li et al investigate the genome, transcriptomes and proteomes of scallop Chlamys farreri, revealing evidences of molecular adaptations to semi-sessile life and neurotoxins.

Human B cells can be edited to produce custom heavy-chain antibodies while allowing the cells to respond to immunization with a matched antigen.

Using scanning tunneling microscopy, the authors observe a short-range checkerboard charge order in the iron-based superconductor (Li_0.84Fe_0.16OH)Fe_1-xSe. They argue that the charge order is likely driven by multiple-Q spin density waves originating from spin fluctuations.

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.

PROTACs have emerged as promising therapeutic agents but their cellular uptake is often inefficient. Here, the authors show that reversible covalent warhead chemistry improves PROTAC intracellular accumulation and target engagement, and develop a dual inhibitor/degrader of Bruton’s tyrosine kinase

The mechanism of high-temperature superconductivity in the iron-based materials remains not fully understood. Here, the authors report on ARPES measurements on an FeSe-based bulk superconductor, whose electronic properties are found to be similar to those of single-layer FeSe/STO films.

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution. Here, the authors demonstrate that physiologic aging induced involution and thermogenic dysfunction result from pyroptotic signalling activation.

SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability.

ABBV-744, a selective inhibitor of the BD2 domains of BET family proteins, is effective against prostate cancer in mouse xenograft models, with lower toxicities than the dual-bromodomain BET inhibitor ABBV-075.

Shin et al. report the molecular mechanics of membrane budding: actin and dynamin pull membrane inward to form a Λ-shape profile; dynamin helices convert Λ- to Ω-shape by constricting Λ’s base, and then constrict Ω-profile’s pore to form a vesicle.