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Previous clinical studies suggested that Insulin-like growth factor binding-protein 7 (IGFBP7) is elevated in early stages of diabetes. Here authors showed tubule and glomerular-specific IGFBP7 promotes diabetic kidney disease.

Abnormal T cell proliferation often triggers autoimmune disorders. Here the authors show that T cell-specific deficiency of the enzyme N-acetyltransferase 10 ameliorates experimental autoimmune encephalitis potentially by RACK1-mediated regulation of T cell metabolism and expansion.

Overcoming the suppressive tumor microenvironment (TME) is crucial to improving the efficacy of cancer therapy. Here the authors show that, in mouse cancer models, administration of exogenous IL-16 establishes a Th1-dominant TME via regulation of glutamine catabolism and triggers a Th1 cell-macrophage crosstalk, enhancing anti-tumor immune responses and the efficacy of immunotherapy.

Inspired by class II aldolases found in nature, the authors report a biomimetic copper/squaramide cooperative catalysis strategy for asymmetric Mannich reactions between challenging acyclic ketimines and α-substituted β-keto esters.

In a phase 1 trial, the co-infusion of CD19-targeting and BCMA-targeting CAR-T cells in adults with treatment-refractory lupus was safe and had promising efficacy, with most patients achieving remission after 3 months.

Wang, Wang, Pan and colleagues uncover a C864–C869 disulfide linkage stimulated by viral RNA that drives RIG-I activation, phase separation and stimulates downstream innate immune signalling.

HER2 targeted therapy combined with chemotherapy represents a standard approach for treating HER2-positive metastatic breast cancer (MBC). Here the authors report the results of a phase II trial of the small molecule tyrosine kinase inhibitor pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC.

Two mGlu3–βarr1 cryo-EM structures with 2:1 and 2:2 stoichiometries are reported, revealing that the inactive state involves mGlu3 engagement of βarr1 through phosphorylated C-terminal tail and intracellular loops.

Quantum information cannot be copied, posing challenges for long-distance communication due to signal losses. Here the quantum relay architecture using a single-photon source enhances the signal-to-noise ratio of quantum information transmission.

Sequencing the genome and microbiome of about 1,500 tick samples from regions across China revealed host–microbe associations in ticks that could have implications for controlling ticks and tick-borne diseases.

The identification of cross-linked peptides at a proteome scale for interactome analyses represents a complex challenge. Here the authors report an efficient and reliable search engine pLink 2 for proteome-scale cross-linking mass spectrometry analyses, and demonstrate how to systematically evaluate the credibility of search engines.

A coherent 909-Hz quasi-periodic oscillation was potentially detected in GRB 230307A, the second brightest gamma-ray burst to date, indicating that a millisecond magnetar formed after the merger powered the burst.

Natural vesicles typically consist of a lipid membrane enclosing substances. Now a coacervate vesicle formed by liquid–liquid phase separation of cholesterol-modified DNA and histones has been developed. Unlike traditional vesicles, these lack a membrane and feature a high-density liquid layer around a water-filled cavity, offering enhanced kinetic stability and potential as a biopharmaceutical delivery system.

P2X3 activation requires tightening the inner pocket of the head domain (IP-HD) following ATP binding. Here the authors demonstrate that targeting the IP-HD with allosteric small molecules presents a potential strategy for the development of therapeutics for refractory chronic cough without taste abnormalities.

The global regulator PhoP plays crucial roles in bacterial pathogenicity. Shi et al. report four cryo-EM structures of PhoP-dependent transcription activation and repression complexes, revealing dual transcription regulation mechanisms of PhoP.

Here the authors propose an atomic-scale electron avalanche breakdown model to investigate the dynamic behaviors of excited electrons under extremely high electric fields in various dielectrics ranging from simple oxides to perovskites.

ARAF uniquely enhances RAS activity via N-terminal disordered sequence, forming membrane ARAF–RAS condensates that shield RAS from negative regulation and drive cancer drug resistance.

In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.

In a randomized phase 2 trial comparing anti-PD-1 plus anti-VEGF plus an HDAC inhibitor versus anti-PD-1 plus an HDAC inhibitor in patients with MSS/pMMR colorectal cancer, the triplet combination led to significantly better 18-week progression-free survival.

The authors report on the structure of a glucocorticoid-bound adhesion G-protein-coupled receptor–G protein complex.

How excitatory neurons (EN) acquire senescence is unclear. Here, the authors show that GDF11 in ENs slows EN senescence, brain ageing, cognitive decline and maintains lifespan, revealing a mechanism underlying EN senescence and brain ageing.

This article presents a polymeric membrane-enclosed insulin crystal equipped with physiological signal-sensing microdomains, dubbed ‘smart drug crystals’, that enables long-term, glucose- and β-hydroxybutyrate-dually responsive drug release for type 1 diabetes therapy.

ZAC is a Zn²⁺ and H⁺-activated cation channel. Here, the authors report the structures of human ZAC and identify an unusual C-tail that functions in auto-inhibition. This work provides insights into the gating and activation mechanisms of ZAC.

Safe haemodialysis is essential for patients with acute kidney injury and renal failure. Here the authors present a DNA origami-based approach with high affinity and specificity to thrombin, inhibiting coagulation.

Hypoxia and immunosuppression contribute to tumor resistance to radiotherapy (RT). Here the authors design a nanoprobe based on NIR-IIb emitting quantum dots for image-guided RT and modified with catalase to relieve hypoxia in the tumor microenvironment, enhancing the precision and efficacy of RT and promoting anti-tumor immune responses.

A heteroepitaxial-strain-based strategy for enhancing the stability of perovskite quantum dots for spectrally narrow (pure) red LEDs is reported.

In plant miRNA biogenesis, DCL1 cleaves pri-miRNA and pre-miRNA sequentially. This study reports the cryo-EM structures of Arabidopsis DCL1 complexed with the two substrates and uncovers the domains that are key for substrate recognition and transfer.

Pangolins are a potential reservoir for viruses with cross-species infection potential. Here, the authors characterize a HKU4-related coronavirus isolated from pangolin and demonstrate its ability to infect human cell lines as well as its potential to infect transgenic mice expressing the human receptor DPP4.

Electronic skins are limited in perceiving liquid sliding information as realistically as humans and provide real-time feedback. Here, Xu et al. developed a self-powered bionic droplet electronic skin with co-layer interlaced electrode networks and overpass connection technology to sense complex water motion.

The interactions between tertiary lymphoid structures (TLS) and tumor cell aggregates remain to be investigated. Here, single-cell and spatial transcriptomics reveal the cellular composition, formation, and function of TLS during tumour progression and immunotherapy response in nasopharyngeal carcinoma.

The controlled in situ formation of biomolecular condensates as intracellular reservoirs for the enrichment and retention of a chemotherapeutic in cancer cells enhanced antitumour activities in mice with drug-resistant tumours.

The assembly of eight high-quality rapeseed genomes allows identification of presence and absence variations (PAVs) and small variations. PAV-based genome-wide association analysis uncovered causal variations for agronomic traits and ecotype differentiation.

Growth hormone-releasing hormone (GHRH) controls metabolism and tissue growth through binding to the cognate receptor (GHRHR). Here authors report the structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein which reveals a characteristic hormone recognition pattern of GHRH by GHRHR.

High-entropy ceramic dielectrics show promise for capacitive energy storage but struggle due to vast composition possibilities. Here, the authors propose a generative learning approach for finding high-energy-density high-entropy dielectrics in a practically infinite exploration space of over 10¹¹ combinations.

The mechanisms through which multigenerational paternal obesity affects spermatogenesis in offspring remain poorly understood. Here, the authors show that it affects Wt1 m6A modifications, decreasing the fertility of offspring.

Transcription activation of late genes in T4 bacteriophage requires the promoter specificity factor gp55, the coactivator gp33 and the sliding clamp gp45. Here, the authors provide structural insights into gp45- dependent transcription activation by determining the cryo-EM structures of a gp55-dependent RNA polymerase (RNAP)-promoter open complex and of an intact gp45-dependent transcription activation complex.

In a prespecified interim analysis of the multicenter, randomized, phase 3 FLAMES trial, maintenance therapy with a PARP inhibitor in patients with ovarian cancer showed prolonged progression-free survival compared with placebo in all subgroups defined by BRCA or homologous recombination status.

Cryo-EM structures of the E. coli ABC transporter LolCDE in different functional states reveal mechanism of lipoprotein transport to the outer membrane of Gram-negative bacteria.

Illuminating internal organs and tissues with high controllability and adaptability remains challenging. Here the authors present a flexible, biodegradable photonic device called iCarP for large area, high intensity, wide spectrum, deeply penetrating, continuous or pulsatile illumination.

The role of chromatin rewiring of regulatory elements in multiple myeloma (MM) remains poorly understood. Here, the authors identify a super-enhancer driven gene, PPP1R15B whose perturbation confers vulnerability in MM cells and suggest it as a therapeutic target.