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Vanishing Chern numbers usually mean that a system is topologically trivial, but this rule may be violated for periodically driven systems. Here, Maczewskyet al.report topologically protected edge modes in a periodically driven photonic lattice with all bands of zero Chern number.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

The discovery of an unusual protist named Solarion arienae, which has a mitochondrial genome with some intriguing features, provides insight into the early radiation of eukaryotic groups.

Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNA^Ala mutation (m.5019A>G) in mice and demonstrate that macrophages carrying this mutation display altered function and metabolism in vitro, along with increased type I IFN release following LPS challenge in vivo.

Bose–Einstein condensates were demonstrated at low temperatures, mostly with ultracold bosonic atoms. Here, the authors demonstrate BEC of photons in a standard 1D erbium–ytterbium co-doped fiber cavity at, below and above room temperature.

The determination of thermal and non-thermal carrier populations in plasmonic systems generally requires assumptions on the types of distributions present. Here, Heilpern et al. directly determine such populations in thin film pump-probe measurements using a double inversion procedure.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

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.

MicroRNAs regulate gene expression through selective pairing with target mRNAs. Here, the authors reveal distinct, mutually exclusive binding modes of miRISC at the 5′ seed and 3′ non-seed regions, advancing understanding of RNA silencing mechanisms.

Carta leverages lineage tracing data to infer the optimal trajectory of cell differentiation.

Proteolysis targeting chimeras (PROTACs) promote the degradation of targets by ensuring the proximity of the E3-ligase and the target, and understanding the structure of PROTACs at the atomic level is key to developing more efficient degraders. Here the authors determine the complete atomic-level structure of an amorphous Von Hippel-Lindau (VHL)-based SMARCA2 PROTAC (PROTAC 2).

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.

Controlling nanoscale interfaces is key for ensuring stable plasmonic and catalytic function yet remains difficult to achieve under operando conditions. Now it has been shown that transient Au–Cl adlayers function as redox-active Au(I) intermediates, modulating interfacial electrostatics. This modulation stabilizes gold nanogaps and directs ligand rebinding, thereby enabling reproducible regeneration of subnanometre architectures.

The poor bench stability of phosphoramidites is a drawback for fast automised chemical oligonucleotide synthesis. Here, the authors report a method for on-demand flow synthesis of phosphoramidites within short reaction times, in near-quantitative yields and sufficient purity for integration with DNA synthesizers.

The authors combine fossil occurrence data, phylogenies and climatic niche modelling to explore the palaeobiogeography of early pterosaurs and their non-flying close relatives, the lagerpetids.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

Ti-, Zr- and Nb-based MXenes with Cl, Br or mixed terminations can be synthesized by a bottom-up, atom-economic route directly from metals and molecular organohalides. The reactivity of organohalide precursors can be controlled to enable direct synthesis of MXene nanostructures that exhibit enhanced surface reactivity compared with conventional micrometre-scale MXenes.

Improved understanding of the tumor ecosystem in glioblastoma is critical for developing new treatment strategies for the disease. Here, the authors identify pericytes as an active paracrine signaling hub within the tumor parenchyma that orchestrates a tumor-suppressive microenvironment, suggesting pericyte preservation as a key feature of future therapeutic regimens for glioblastoma.

Observations of the shape, topography, crustal thickness and surface composition of the South Pole–Aitken impact basin on the Moon suggest a southward impact trajectory and the excavation of a discontinuous remnant magma ocean from beneath the crust.

The relation between the microscopic structure and the optical properties of atomic defects in 2D semiconductors is still debated. Here, the authors correlate different fabrication processes, optical spectroscopy and electron microscopy to identify the optical signatures of chalcogen vacancies in monolayer MoS2.

A prototypical example of a ‘strategic atom replacement’ approach enables synthesis of N-alkyl pyrazoles from isothiazoles by swapping the sulfur atom with a nitrogen atom and its associated alkyl fragment to deliver the alkylated pyrazole.

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.

Reduced abundance of immune-stimulating gut bacteria ameliorated the inflammatory and autoimmune phenotypes of mice with mutations in C9orf72, which in the human orthologue are linked to amyotrophic lateral sclerosis and frontotemporal dementia.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Boron is known to form a wide variety of molecular structures. Here, the authors observe the highly symmetric cobalt-centered boron drum-like structure of CoB₁₆⁻, characterized by photoelectron spectroscopy and ab initio calculations, in which the cobalt atom is sixteen-coordinate.

Benzothiophenes are common motifs in bioactive compounds, but selective functionalization at C3 is challenging. Here the authors report a method starting from benzothiophene S-oxides via an interrupted Pummerer reaction, giving access to a range of C3-alkylated and -arylated products.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Breather solitons can be found in both physical and biological nonlinear systems. Here, Yuet al. demonstrate this type of soliton in silicon and silicon nitride microresonators, which advances the understanding of soliton-based comb-generation in microresonators.

Human airway contains physiologically relevant yet rare cells, but their scarcity prevents thorough profiling and differentiation studies. Here the authors use single cell RNA sequencing to identify rare ionocytes and tuft cells, as well as a potential progenitor population with cytokine-guided differentiation into either the ionocytes or tuft cell lineage.

Synthetic dimensions allow photons and gauge fields to interact in photonic emulators. Now a study with fast-gain lasers shows that gain-driven coherence enables robust light flow in frequency space, establishing it as a viable platform for lattice emulation.

Terahertz-frequency communications promise ultra-high data rates and stable latency, yet current systems lag behind infrared technologies. Here, the authors demonstrate a pioneering multi-gigabit-per-second free-space optical communication using a terahertz quantum cascade laser, setting the stage for advanced wireless networks with significant implications for high-speed data transmission.

Enterololin is a narrow-spectrum antibiotic that selectively kills Enterobacteriaceae in vitro and in a mouse model of adherent-invasive Escherichia coli gut infection. AI-guided mechanism-of-action studies identified LolCDE as its molecular target.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Supercapacitors are fast-charging energy-storage devices. However, an understanding of how structure impacts high-power energy storage is still lacking. Here pulsed-field-gradient nuclear magnetic resonance measurements show that the pore network tortuosity, rather than traditional porosity analyses, in porous carbon dictates the speed of supercapacitor charging.

The Tnf^ΔΑRE mice overexpress TNF, resulting in ileitis, showing strong similarity to Crohn’s disease in human patients. Here authors describe the immune pathology of the murine disease model by single-cell RNA sequencing, spatial and functional experiments to find that spatially distinct subsets of fibroblasts initiate the disease and drive disease progression.

Radiation sources driven by laser-plasma accelerators have the potential to produce shorter bursts of radiation at lower cost than those based on conventional accelerators. Schnell et al.demonstrate the ability to control the polarization of the bursts of hard X-rays produced by such a source.

Antimicrobial resistance continues to be a critical One Health challenge, despite research and policy progress. Building on the past decade of research, this Perspective provides an integrative roadmap for addressing antimicrobial resistance by leveraging the complexities of human and environment interactions.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

GTPase-activating proteins (GAPs) often contain regulatory PH domains. In this work, Soubias et al, using an integrated structure-function approach, discovered a mechanism where a GAP PH domain binds directly to a GTPase to induce allosteric changes facilitating GTP hydrolysis.