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The study identified and structurally characterized the UDP-glycosyltransferases (UGTs) responsible for regioselective glycosylation of wolfberry-derived bioactive lycibarbarspermidines, elucidating the molecular basis for their substrate specificity.

Lithium bis(trifluoromethanesulfonyl)imide is used as a conducting salt for rechargeable lithium metal batteries because of its stability, but corrosion with aluminium current collectors is an issue. A non-corrosive sulfonimide salt is shown to suppress anodic dissolution of an Al current collector at high potentials while improving cycling.

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.

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.

Metal-organic frameworks can be used to develop high-performance membranes. Here, authors demonstrate a dual-source seeding method to fabricate MOF-303 hollow fiber membranes with controlled crystallographic orientation, superior water flux, selectivity, and structural stability for pervaporation and nanofiltration.

The adaptor protein TRADD is a regulator of both cellular homeostasis and apoptosis, and represents a potential therapeutic target for human diseases.

Two segments from FUS LC are shown to form reversible fibrils. The structural bases for this behavior and for its regulation by phosphorylation is revealed using X-ray and microelectron diffraction.

An electronic skin that is capable of long-term monitoring of vital signs and molecular biomarkers in sweat can—with the help of machine learning—be used to classify stress responses with high accuracy and predict state anxiety levels with high reliability.

Several in vitro synthetic enzymatic biosystems (ivSEBs) to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA) have been reported, but suffer from complicated operation procedures, low yields, and/or dependence on costly ATP. Here, the authors report the design of an ATP-free ivSEB for one-pot, high-yield PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate.

Immune checkpoint inhibitors have now been approved for the treatment of advanced hepatocellular carcinoma (HCC), however only a minority of patients appear to benefit. Here the authors report that RNase1 levels predict response to nivolumab (anti-PD1) in patients with HCC and that RNase 1 overexpression correlates with an immunosuppressive tumor microenvironment in HCC preclinical models.

Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

Broadly neutralizing antibodies are potential therapeutics and can aid rational vaccine development. Here, the authors show that the human monoclonal antibody H3v-47 recognizes a highly conserved epitope in HA of H3N2 viruses, inhibits virus replication by blocking egress and other mechanisms, and protects mice from disease.

The tRNA synthases AARS1 and AARS2 are identified as evolutionarily conserved sensors of intracellular l-lactate to mediate the global lysine lactylome.

Chronic rhinosinusitis (CRS) has clinical presentations with and without nasal polyps (NP). Here the authors characterize human CRS with NP (CRSwNP) and show that neutrophil associated disease is characterized by IL-1 signaling via fibroblasts and epithelial cells, and that a similar phenotype and functional profile can be demonstrated in mouse models.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Traditional catalytic techniques often encounter obstacles in the search for sustainable solutions for converting CO₂ into value-added products because of their high energy consumption and expensive catalysts. Here, we introduce a contact-electro-catalysis approach for CO₂ reduction reaction, achieving CO Faradaic efficiency of 96.24%.

Apical membrane antigen-1 (AMA1) is important for Plasmodium parasite invasion, but surface polymorphisms in P. falciparum AMA1 hamper vaccine and antibody development. Here the authors identify a humanised single-domain antibody molecule, an i-body, that binds to AMA1 of all Plasmodium parasites examined and inhibits parasite invasion.

The E3 ubiquitin ligase MDM2 inhibits the tumor suppressor p53 and is an important therapeutic target. Zou and colleagues demonstrate that MDM2 also has a T cell-intrinsic role that supports antitumor responses.

Engineering 2D heterostructures with unique physiochemical properties and molecular sieving channels is one approach for designing membranes selective gas molecule transport. Here authors arrange graphene and boron nitride nanosheets in an alternating pattern, resulting in narrow porous nanochannels and excellent hydrogen separation properties.

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.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Cryo-EM structures of the RAG endonuclease in complex with intact DNA substrates reveal that DNA melting is the first step in V(D)J recombination, a mechanism potentially conserved in retroviral integration and DNA transposition.

Lithium battery performance hinges significantly on the solvation structure of the electrolyte and the resulting interphase. Here the authors introduce a fluorinated ether with minimal lithium-ion coordination and enhanced electrochemical stability, thus improving both cyclability and calendar life.

Lack of stability in RuO₂-based catalysts at industrial currents impedes their use in green hydrogen production. Here, the authors show that incorporating lanthanide elements into RuO_x shields against external factors, enabling fine-tuned Ru-O covalency for durable oxygen evolution reaction electrocatalysis.

Recently discovered type III-E CRISPR–Cas systems use the single Cas7-11 effector to cleave foreign RNA. Here the authors use cryo-electron microscopy and biochemical approaches to reveal the mechanisms underlying crRNA maturation, target RNA recognition and cleavage, and communication with the protease Csx29 by Cas7-11.

The balance between apoptosis and autophagy is critical for normal development, proper tissue function, and disease pathogenesis. Here, the authors show previously unannotated BIRC6 domains, including a ubiquitin-like domain, and how it utilizes its ubiquitylation function to regulate both apoptosis and autophagy.

The balance between osteoclast and osteoblast-mediated bone turnover is essential for bone health and homeostasis. Here the authors show that both germline and osteoblast-specificSmurf2-deficient mice have osteoporosis as a result of increased osteoblast RANKL production and excess osteoclastogenesis.

For the object recognition in lightless environments, the authors propose the olfactory-tactile machine learning approach, inspired by the star-nose mole’s neural system. They show how bionic flexible sensor arrays allow for real-time acquisition of object’s form and odor when touching it.

Weng et al. developed a photocaged lysine-based gain-of-function strategy termed DeKinomics to systematically dissect kinase activity with high specificity and temporal resolution under living conditions.

Dumitru et al. probe the ligand-binding mechanism and activation of the human G protein-coupled C5a receptor (C5aR) and discover a cooperativity between the two orthosteric binding sites. Their findings, probing the dynamic aspects of receptor–ligand interaction, are valuable to develop a better understanding of GPCR activation and signalling.

Pancreatic ductal adenocarcinoma (PDAC) cells can utilise the tumour microenvironment to metastasise to the liver. Here the authors show that hepatoctyes overexpress SLIT2 to enable premetastatic niche formation for ROBO1-positive PDAC cells to support the survival of these tumour cells in the liver.

The phage phi3T peptide SAIRGA directs the lysis–lysogeny decision by modulating conformational changes in phAimR, whereas the SPbeta peptide GMPRGA regulates the lysis–lysogeny pathway by stabilizing spAimR in the dimeric state.

Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme and catalyzes 5α-reduction of testosterone to dihydrotestosterone. Structural analysis accompanied by computational and mutagenesis studies reveal the mechanisms of catalysis and inhibition by clinically relevant drugs targeting SRD5A2.

Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of inflammatory diseases. Here authors report a cryoelectron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, which provides insights into PACAP27 binding and VIP receptor activation.

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.

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.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.