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Simultaneous profiling of spatial transcriptomics (ST) and metabolomics (SM) offers a novel way to decode tissue microenvironment heterogeneity. Here, the authors present SpatialMETA, a conditional variational autoencoder-based framework designed for the integration of ST and SM data.

Material properties and structural rigidity make topological transitions hard to scale and program. Here, authors use moiré superlattices of optical skyrmions to achieve broad tuneability of topological transitions and revealing a symmetry-related selection rule for the system topological invariants, excluding integer multiples of 3/2.

This study reports DLFea4AMPGen, a peptide design strategy that leverages deep learning to identify and extract key features for the generation of new antimicrobial peptides (AMPs), which allowed for the identification of 12 AMPs with bioactivity.

The role of TGFβ in cancer is paradoxical and context-dependent. Here, the authors discover that a preserved, DLD-mediated metabolic suppression by TGFβ undermines anti-TGFβ therapy, promoting gastric cancer growth.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

Developing photocatalysts from earth-abundant materials is crucial for sustainable solar hydrogen production, yet challenges in efficiency and stability persist. Here, the authors report that the topological semimetal cobalt triarsenide functions as an active and durable platform for this reaction.

In this work, Zhang, Jia, Wang et al. show that MORCs stabilize PRC2 preferentially at bivalent domains to maintain high levels of H3 K27 trimethylation and form chromatin loops for gene repression and stress tolerance, and are counteracted by ALKBH1, a DNA 6mA demethylase.

All-in-one computing, which merges sensing, linear computing, and nonlinear activation, is a critical goal for next-generation AI hardware. Here, Zhang et al. introduce a high-speed, reconfigurable split-floating-gate memory, enabling multi-function integration within a unified platform and hardware native neuromorphic processing.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

This work enables multi-target, ultra-fast optical wireless communication with a chip-scale device. The system delivers 320 Gbps speeds and robust video transmission, providing a solid-state solution for future high-capacity networks.

Streptococcus equi subsp. zooepidemicus imports glucose via the bacterial mannose phosphotransferase system (PTS_man), which inhibits stringent response, supports growth in cerebrospinal fluid and promotes brain damage during meningitis.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Atropisomers with a chiral C-N axis are useful for natural products synthesis and as ligands in asymmetric catalysis. Here, the authors reportt a π-π interaction and dual H-bond concerted control strategy in enantioselective C-H amination affording configurationally stable N-C atropisomers.

Small peptide tags (like ALFA) cause minimal disruption of proteins, but they typically lack fluorescence, which would enable knockin screening. Now, antigen-stabilizing fluorescent protein-fused nanobodies called ANGEL have been developed, which enable endogenous labeling guided by ALFA nanobodies. ANGEL fluorescence increased with genomic ALFA in-frame insertion, which enables fluorescence-activated cell sorting screening for knockins, endogenous protein labeling, imaging, degradation and interactome analysis in native cellular contexts.

Natural products often contain complex N-fused polycyclic structures with multiple substituents and stereocentres. Here, the authors developed a bifunctional organocatalyst that is instrumental in obtaining such structures and applied it to the total synthesis of naucleofficine I and II in 6 steps.

Hepatitis B virus X protein (HBx) binds anti-apoptotic Bcl-xL through its BH3-like motif to promote viral replication. Here, the authors provide the structure of the HBx BH3-like domain and Bcl-xL, which shows an unusual mode of interaction, and identify a short peptide that inhibits HBV replication in cultured human hepatic cells.

Chiral vicinal amino alcohols are found in many bioactive compounds and may serve as chiral ligands. Here, the authors report a photocatalytic enantioselective cross-coupling of nitrones with aromatic aldehydes with a chiral ligand-coordinated rare earth ion synergistically producing enantiopure vicinal amino alcohols.

Visualizing mechanical stress distribution in soft and live biomaterials is key to understand biological processes and improve material design. Here, the authors design a biosensor to visualize the stress distribution in soft biomaterials and living tissues.

Intestinal motility disorders that can occur following small intestine resection often require regular monitoring. This study reports a biodegradable ultrasound contrast tape (BioUCT) that adheres to the intestine for high-contrast imaging for up to two weeks for non-invasive monitoring of postoperative intestinal motility.

In mitochondria transplantation, the limited activity and yield of mitochondria constrain their clinical application for mitochondrial diseases. Here, authors develop a method for producing mitochondria-enriched extracellular vesicles, which offer high-quality, abundant mitochondrial material for transplantation.

Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.

The energy disorders in the lateral direction of the junction in large-area photovoltaic modules are largely overlooked. Here, authors employ organic amidinium passivators to suppress the micro-inhomogeneity in the lateral energy landscapes and achieve high performance stable perovskite solar cells.

Achieving generality in asymmetric catalysis with highly reactive radicals is a challenge. Now it is shown that a sequential copper-catalysed approach enables the efficient, enantioselective cross-coupling of over 50 diverse radicals, providing unified access to C-, P- and S-chiral products and advancing the asymmetric synthesis of challenging molecular architectures.

Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.

The crystallization mechanism at reduced dimensions remains poorly understood. Here, the authors use AFM and MD simulations to elucidate the nucleus-free crystallization of two-dimensional ice at atomic resolution.

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

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.

Ubiquitin tagging controls protein fate, but how the COP1-DET1 E3 ligase works was unclear. Here, the authors present cryo-EM structures of an inactive stacked assembly that switches to an active dimer on substrate binding, with DET1 guiding enzymes to start and co-workers to extend ubiquitin chains.

A two-dimensional van der Waals material, NbOCl₂, that simultaneously exhibits near-unity linear dichroism (~99%) over 100 nm bandwidth in ultraviolet regime and large birefringence (0.26–0.46) within a wide visible–near-infrared transparency window is reported.