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Mammalian 5′-AMP-activated protein kinase (AMPK) is a nutrient sensor and a therapeutic target for Type 2 Diabetes. Here the authors report that intestinal AMPK modulates brown adipose tissue thermogenesis through anti-microbial peptide controlled gut microbiota and may partially underlie the anti-diabetic effects of metformin.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Visceral adiposity is associated with metabolic diseases, whereas subcutaneous adiposity is comparatively benign. Here, the authors report that subcutaneous adipose tissue adopts visceral-like characteristics in response to prolonged fasting, and show this is mediated by miR-149-3p and its target, PRDM16.

Short-wavelength spin waves with high group velocity are one of the key ingredients for the spin-wave based memory-logics. Here the authors demonstrate the propagation of spin waves with wavelength down to 50 nm and group velocity up to 2600 m s⁻¹ using ferromagnetic nanowires grown on a thin Y₃Fe₅O₁₂ film strip structure.

The development of a new smallsample learning framework, KprFunc, leads to the discovery of an important role for lysine propionylation in determining global protein homeostasis, mediated by a critical propionylation site on histone H2B, H2BK17pr.

Acorales is sister to all other monocots and contains only one family with just one genus, Acorus. Here, the authors assemble the genome of the diploid Ac. gramineus and the tetraploid Ac. calamus, reconstruct an ancestral monocot karyotype and gene toolkit, and discuss the origin and evolution of the two species and other monocots.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

The low activity of PylRS hinders the efficient production of ncAA containing proteins. Here, authors apply machine learning to engineer the tRNA-binding domain of PylRS, obtaining variants with improved stop codon suppression efficiency and achieving higher yields of proteins containing various ncAAs.

Early-stage liver metastasis of pancreatic ductal adenocarcinoma (PDAC) makes radical surgery not efficacious. Here, the authors show that MLKL-driven necroptosis contributes to PDAC early-stage metastasis by inducing tumour CD47 upregulation and macrophage extracellular traps formation.

Inspired from bimetallic active sites in both enzymes and heterogeneous catalysts, the development of binuclear catalysis can offer the potential to induce novel intermediates, reactivity, and selectivity. Here the authors report a dimerization-hydrocarbofunctionalization of internal alkynes via dinickel catalysis, leading to the formation of pentasubstituted 1,3-dienes.

Elucidation of drought tolerance mechanism would help to develop tolerant crops. Here, the authors reveal the interaction between BBX18, a zinc finger transcription factor, and ascorbate peroxidase (APX1) to mediate drought stress resistance in tomato.

In locusts, the aggregation pheromone 4-vinylanisole is derived from dietary phenylalanine, and its production is dependent on two 4-vinylphenol methyltransferases that are potential targets for locust pest control.

Existing isokinetic training devices are often heavy, bulky, and energy-consuming, which limits the rehabilitation opportunities only at designated hospitals. Here, the authors show a highly integrated and power-free knee rehabilitation robot that can provide home-based isokinetic training

The high-throughput identification of cross-linking peptides is challenging. Here, the authors developed an enrichable and cleavable latent bioreactive unnatural amino acid eFSY, and a software AixUaa to improve the cross-linking peptides indentification in live cells.

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.

Radiographic imaging is routinely used to evaluate treatment response in solid tumors. Here, the authors present a multi-task deep learning approach that allows simultaneous tumor segmentation and response prediction from longitudinal images in a multi-center study on rectal cancer.

Boron nitride nanosheets possess high in-plane thermal conductivity and high thermal contact resistance. Here the authors discover obliquely aligned nanosheets at the interface can act as a phonon bridge to lower the contact resistance.

For over half a century, temperature wave was deemed exotic and mattered only at extremely low temperatures. Here, the authors reported direct observation of second sound, signature of the temperature wave, at a record-high temperature of over 200 K.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

A mechanism is uncovered that results in fetal hepatocytes having a paracrine role in providing genome protection to haematopoietic stem and progenitor cells.

Treating Alzheimer’s disease, one of the most common neurodegenerative diseases, is of wide interest. Here, the authors report on the development of casein coated gold nanoparticles which were able to cross the blood brain barrier and protect against amyloid beta toxicity in a zebrafish model.

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.

Diels-Alderases (DAs), enzymes catalyzing [4 + 2] cycloaddition reactions, are of high interest, but insights into their evolution are lacking. Here, the authors investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites, suggesting they evolved from an ancestor functioning as a flavin adenine dinucleotide-dependent oxidocyclase.

Cheng et al. developed an autophagy-based targeted protein degradation platform by conjugating polyethylenimine to antibodies, designated as autophagy-inducing antibodies, which can degrade proteins in vivo and enable the degradation of multiple proteins at the same time.

This study reports endothelial leakiness in vitro, in silico and in vivo, where adherens junctions are disrupted by their exposure to the anionic oligomers and seeds of Alzheimer’s amyloid beta, preceding proinflammatory and pro-oxidative events.

Ding and colleagues show that somatic cell reprogramming does not depend on Atg5-dependent canonical autophagy, but requires mitochondrial clearance in an Atg5-independent manner downstream of AMPK.

TRPV1 has been associated with proliferation and survival of tumors, and can be activated by heat and other stimuli. Here, the authors block TRPV1 using photothermal nanoparticles encapsulating a TRPV1 antagonist in different cancer types, which can enhance thermo-immunotherapy in pancreatic cancer models.

The correlated errors in superconducting qubits have been linked to high-energy particle impacts from cosmic rays, but a direct observation has been lacking. Here, the authors measure the quasiparticle bursts and correlated errors and separate the contributions of cosmic-ray muons and γ-rays in a 63-qubit processor.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Covalent organic frameworks are used in capture of radioactive ions but achieving high separation factors remains challenging. Here, the authors design an ionic COF its neutral non-ionic to better understand the role of different N sites on the selective capture of Th(IV) and report remarkable separation factors ranging from 10² to 10⁵.

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.

A transformer-based approach called Translatomer is presented, which models cell-type-specific translation from messenger RNA expression and gene sequence, bridging the gap between messenger RNA and protein levels as well as providing a mechanistic insight into the genetic regulation of translation.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Non-random chemical mixings that are intrinsic to medium- and high-entropy alloys are difficult to detect and quantify. Here the authors perform a diffraction data-mining analysis, revealing nanoclusters of short-range orders in a CrCoNi alloy, and their impacts on chemical homogeneity and dislocations slip.