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Preferred orientation in cryo-EM often limits structural resolution. Here, the authors present cryoPROS, a novel computational method that co-refines raw and deep generative auxiliary particles to correct misalignment, enabling near-atomic resolution from challenging datasets.

Chiral and hindered triazolopyridinone derivatives are an underexplored area of chemical space mainly due to their challenging synthesis via classical methods. Here, the authors report an electrochemical rearrangement for the synthesis of triazolopyridinones using diverse, available alkyl carboxylic acids as starting materials.

Nucleoli are essential cellular sites for ribosome biogenesis that are formed by liquid-liquid phase separation. Here the authors show that METTL3/METTL14 maintain nucleoli integrity through mediating SUV39H1/2 degradation in human embryonic stem cells.

The G9a-like lysine methyltransferases can be inhibited by the small molecule BIX-01294, recently identified through a chemical screen and shown to be capable of replacing Oct3/4. The structure of GLP in complex with BIX-01294 indicates an overlap with the known position of histone peptide binding, and further work indicates that the drug inhibits methylation of DNMT1, indicating that it is enzyme specific but non specific with regard to substrate.

Neurogenesis is an ordered transition from pluriptotent cells to neural precursor cells (NPCs) to neurons. Here the authors show that loss of the lysine demethylases JMJD3 and UTX leads reduced DNA accessibility at neurogenesis loci in human NPCs, and that the chromatin remodeller BAF can rescue differentiation defects.

Loss of the E3 ubiquitin-protein ligase ARIH1 has been associated with cancer escape from anti-tumor immunity. Here the authors show that ARIH1 mediated ubiquitination and degradation of DNA-PKcs trigger activation of STING pathway in tumor cells, sensitizing tumors to immune checkpoint blockade.

This study has identified new regulators, such as RHD6 and GL2, involved in the regulation of the RAE1-STOP1-ALMT1 module, contributing to Al resistance. It has also established a complex transcriptional network that controls STOP1-dependent ALMT1 expression, offering new insights into Al resistance and signaling.

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. Here, the authors show mazdutide was well tolerated over 24 weeks and demonstrated significant and clinically meaningful body weight loss, compared with placebo, in Chinese overweight adults or adults with obesity.

The dynamic protein corona hinders the uptake of nanocarriers in desired target cell populations, limiting their bench-to-bedside translation. Here the authors reveal that the modification of hydroxyl and amino functional groups on nanovesicles can rationally regulate the composition of protein coronas to improve the efficiency of targeted drug delivery.

Developing biointerfaces that combine the advantages of both monolithic and focal elements remains challenging. Now, a hydrogel that releases surface-modified granules and shows biointerface transition capability has been developed. This granule-releasing hydrogel manages colitis, accelerates wound healing, and facilitates cardiac tissue regeneration and mapping of cardiac activity with bioelectronic devices.

Patients with advanced esophageal cancer have poor prognosis and limited treatment options. This randomized, phase II trial compares the efficacy and safety of the anti-PD-1 antibody sintilimab versus chemotherapy in Chinese patients with esophageal squamous cell carcinoma after first-line therapy

Hsc70 (heat shock protein family A member 8) is a cytoplasmic chaperone protein involved in endosomal micro-autophagy and chaperone-mediated autophagy. Here the authors report that Hsc70 promotes lysosomal degradation of PD-L1 and that its overexpression promotes anti-tumor immune responses in preclinical cancer models.

The methylation of DNA and histone H3 lysine 9 in chromatin are positively correlated. This study shows that the DNA methyl transferase Dnmt3a is methylated, and a crystal structure of Dnmt3a bound to the chromodomain protein MPP8 suggests a molecular mechanism.

Off-the-shelf CAR-NKT cells for cancer immunotherapy are advanced toward clinical translation.

CO₂ conversion into value-added chemicals is a promising strategy to exploit renewable feedstocks. Here, the authors report the iridium-catalysed synthesis of higher carboxylic acids from ethers, CO₂ and H₂.

The amphiphilic low-molecular-weight protein hydrophobin (HFBI) can self-assemble into a crystalline monolayer film. Here, the authors present a cryo-EM support film using such 2D crystals of hydrophobin HFBI and show that it protects specimen from the air-water interface and can help to overcome the preferred orientation problem of particles in cryo-EM.

Here the authors develop an iterative particle sieving method called CryoSieve, demonstrating this method outperforms other cryo-EM particle sorting algorithms to reveal that most particles are unnecessary in final stacks.

Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.

Polycomb repressive complex 2 (PRC2) plays an essential role in development by modifying chromatin but what this means at a cellular level is unclear. Here, the authors show that ablation of PRC2 genes in human embryonic stem cells and in mice results in changes in pluripotency and the primed state of cells.

The systemic administration of haematopoietic stem cells conjugated to anti-PD-1-decorated platelets in leukaemic mice promotes the delivery of the checkpoint inhibitor to the bone marrow and suppresses the growth and recurrence of leukaemia.

A solution-based lithography-assisted epitaxial-growth-and-transfer method is used to fabricate single-crystal hybrid perovskites on any surface, with precise control of the thickness, area and chemical composition gradient.

The genome of the biofuel crop switchgrass (Panicum virgatum) reveals climate–gene–biomass associations that underlie adaptation in nature and will facilitate improvements of the yield of this crop for bioenergy production.

A single removable transdermal patch bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix regulates blood glucose in insulin-deficient diabetic mice and minipigs.

Amorphous metal catalysts often exhibit appealing catalytic properties, however, accurate control synthesis of amorphous nano-metal catalysts is a challenge. Here, the authors report a feasible strategy to prepare the amorphous Cu catalysts by supercritical CO₂ treatment followed by electroreduction. The resulted catalyst shows high selectivity towards multi-carbon products for CO₂ electroreduction.

DNA methyltransferase-1 (DNMT1) is involved in CpG methylation, and its stability is known to be regulated by lysine methylation. Now it has been shown that methylation of DNMT1 and AKT1 phosphorylation of DNMT1 are mutually exclusive and that antagonism between these modifications affects DNMT1 turnover.

Kinetics of cargo degradation in phagosomes are measured through engineered RotSensors, capturing their translational and rotational dynamics in parallel.

A deep learning approach that predicts high-resolution maps of rare conformations in cryo-EM by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions.

Chemical-exfoliated borophene and its application in multi-imaging guided photothermal therapy.