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Zhang, Huang, Wang, Long et al. report that NAT10 enhances serine uptake and biosynthesis in an ac4C-dependent mechanism, thereby promoting stemness and progression in acute myeloid leukaemia.

Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein the authors report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in NAFLD patients.

Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.

Results from the precision oncology ARROW trial identify the RET receptor tyrosine kinase as a tissue-agnostic target and the drug pralsetinib’s potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion–positive solid tumors.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Zhang et al. identify GLP-1 receptor agonists mitigating Alzheimer’s disease-related cognitive decline and amyloid pathology in a transgenic mouse model via promoting phagocytosis and through activation of the CaMKK2–AMPK signaling pathway.

Frequencies for motor kinematics are encoded by the cerebellum through population tuning of firing probabilities, which leads to cerebellar oscillations and corresponding motions.

Adélie penguins are a key Antarctic indicator species, but data patchiness has challenged efforts to link population dynamics to key drivers. Che-Castaldo et al. resolve this issue using a pan-Antarctic Bayesian model to infer missing data, and show that spatial aggregation leads to more robust inference regarding dynamics.

Artificial intelligence-based detection of gastric cancer at different stages from noncontrast computed tomography is suggested to be feasible in a retrospective analysis of large and diverse cohorts, including real-world populations in opportunistic and targeted screening scenarios.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

Ovarian and endometrial cancers with CCNE1-amplification are often resistant to standard treatment. Here, the authors identify that CCNE1-amplified gynecological cancer is sensitive to combined PKMYT1 and ATR inhibition via CDK1 activation, resulting in premature mitosis, DNA damage, cell apoptosis and reduced tumour growth and metastasis.

Tao et al. study the role of TRMT6 in colorectal cancer, where it is upregulated and show that TRMT6 supports histone biosynthesis by stabilizing tRNA-Lys-TTT-1-1. Targeting TRMT6 reduced histone mRNA translation in a codon-biased manner.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Lewis acid catalyzed tittle reaction of 1,3-dicycloalkenlidine ketones is recognized as so far the shortest and most effective 1-step method for construction of angular tricyclic scaffolds, which are extensively found in bioactive terpenoids. Here, the authors disclose the structure-reactivity relationship and a regioselectivity predicting model based on in situ IR technology, DFT calculations and machine leaning algorithms.

Toxic protein aggregation is a hallmark of various neurodegenerative diseases. Here, authors show that ATP-independent membrane protein chaperones can serve as a simple design platform for targeting proteotoxic aggregates linked to Huntington’s disease.

Glycosylated asparagine residues that mediate the function of the B7H3 protein are unclear. Here the authors identify the important N-glycosylation sites for B7H3 cell surface localization and T cell inhibition, followed by the development of N91/309 and N104/322 preferentially targeting monoclonal antibody manifesting enhanced antitumor immunity.

Lu et al. investigate the involvement of liquid–liquid phase separation in the progression of triple-negative breast cancer and find that phosphorylated histone deacetylase 6 forms condensates that affect chromatin accessibility and oncogenic transcriptional programs.

A quantitative fluorescence-activated cell sorting method for generating fully human conformational antibodies against amyloid aggregates associated with neurodegenerative disorders—without the need for immunization—has now been developed. Engineered antibodies obtained using this approach show properties rivaling those of clinical-stage antibodies specific for tau and α-synuclein amyloid aggregates.

Though triboelectric technology is attractive for designing next-generation electronic textiles, current devices do not meet performance requirements. Here, the authors report all-fiber e-textiles featuring a triboelectric/ferroelectric synergistic effect for optimizing performance and wearability.

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 molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.

Lactylation of NBS1 by TIP60 promotes homologous recombination-driven DNA repair and resistance to chemotherapy in cancer cells and links altered cancer cell metabolism to increase genome stability.

Antiviral approaches against entire genera or families of viruses need to be constantly developed and innovated. Focusing on several distantly-related orthoflaviviruses, the authors develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once.

Hsu, Wang, Manne et al. identify ALDH4A1 as a component of the mitochondrial pyruvate carrier complex, which plays a non-canonical role in regulating pyruvate homeostasis in mitochondria, TCA cycle entry and tumour suppression.

Polymer crosslinking in desalination membranes adds stability on the cost of molecular transportation rates through the membrane. Here the authors tailor crosslinking of desalination membranes to overcome the stability and transport trade-off, and demonstrate a pervaporation desalination thin-film composite membrane with high water flux.

Genome-scale CRISPR–Cas9-based synthetic lethality screens identify PKMYT1 as a potential therapeutic target in tumours with CCNE1 amplification.

Lipoic acid is a food supplement and approved neuropathy drug but lacks known molecular targets. Here, Lechner et al. employ chemoproteomic target deconvolution to demonstrate that (R)- but not (S)-lipoic acid stereoselectively inhibits histone deacetylases at physiologically achievable doses.

Circulating tumour cells can be useful for monitoring disease progression but how they survive in the circulatory system is unclear. Here, the authors use single-cell sequencing of circulating tumour cells from multiple vascular sites in liver cancer patients and identify genes that may help the cells survive.

An ultra-rapid 3D immunostaining protocol can uniformly label organ-scale tissues.

Numerous tissues are derived from the lateral plate mesoderm (LPM) but how this is specified is unclear. Here, the authors identify a pan-LPM reporter activity found in the zebrafish draculin (drl) gene that also shows transgenic activity in LPM-corresponding territories of several chordates, including chicken, axolotl, lamprey, Ciona, and amphioxus.

Analysis of pre- and post-chemotherapy samples collected from 22 patients with high-risk neuroblastoma using single-nucleus RNA and ATAC sequencing and spatial omics characterizes therapy-related changes in cell composition and the tumor microenvironment.

APOL9a/b proteins coat mouse intestinal bacteria with high specificity, and genetic abolition of ceramide-1-phosphate synthesis pathways in the symbiote Bacteroides thetaiotaomicron significantly decreases this binding of APOL9a/b to the bacterium.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Influenza genetic diversity is a key challenge in the design of a universal influenza vaccine that protects against different strains of influenza virus. Here, Malouli and colleagues demonstrate use of a cytomegalovirus-based T cell vaccine that induces immunity and can protect macaques from lethal avian influenza challenge with heterologous strains of influenza and suggest protection is linked to the generation of lung-resident influenza-specific CD4⁺ T cells.

Artificial intelligence (AI) is becoming increasingly relevant to assist with oncology imaging, but diagnosing rare tumours remains challenging. Here, the authors develop an AI approach to detect rare thyroid cancer subtypes by integrating clinical knowledge with image generation based on ultrasound imaging data from large patient cohorts.