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CRISPR base editors are limited by protospacer adjacent motif (PAM) sequences and specific editing windows. Here, authors developed ABE-Ultramax, a suite of adenine base editors with high efficiency, low indel rates, and flexible PAM requirements, enabling precise biallelic editing in zebrafish.

G-quadruplexes (G4s) are stable structures that can disrupt genome stability and are dissolved by helicases. Here the authors present the structure of the yeast helicase Pif1 bound to a G4 and reveal a conserved G4 interacting region.

The genetic basis of how cells replicate their DNA is not well understood. Here, the authors identify >1000 genetic elements that control human replication and reveal a complex epigenetic system that regulates replication origin activities.

Optical communications and quantum operations require active coupling control in closely packed integrated photonic circuits. Here, Mrejen et al.exploit adiabatic elimination to demonstrate active coupling control between two closely packed waveguides by tuning the mode index of an in-between decoupled waveguide.

It is challenging to remove Per- and polyfluoroalkyl substances (PFAS) from water. Here, authors developed a polymer sorbent capable of selectively and efficiently removing PFAS from contaminated water sources to levels below detection limits.

Orbitally frustrated states have been predicted to occur in twisted bilayer graphene. Now these states have been observed for fractional filling of the electronic bands, and exhibit charge- and magnetically ordered phases.

An experiment with atoms and photons provides a fully tunable and microscopically controllable platform for the experimental study of the interplay of superfluidity and density-wave order.

In this work, the authors use a centrifuge force microscope for high-throughput single-molecule experiments to elucidate stacking energies between individual bases of DNA.

Lowering the levels of disease-promoting proteins is generally assumed to be beneficial. The authors developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic locus. This approach was used to study the effect of BACH1 levels on MDA-MB-231 human breast metastatic cells.

DNA mutations induced by dysregulated APOBEC3 expression are associated with tumour-progression and therapeutic resistance, but also with the generation of neoepitopes. Here, the authors show that APOBEC3 function can be exploited in a vaccine setting to generate heteroclitic neoepitopes, enhancing sensitivity to immunotherapy.

Multiplexable barcodes for electron microscopy are applied to brain imaging.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Vectorial optoelectronic metasurfaces are described, showing that light pulses can be used to drive and direct local charge flows around symmetry-broken plasmonic nanostructures, leading to tunable responses in terahertz emission.

This study reports a motif of local field potentials that maps onto the anatomical layers of the cortex, is preserved across macaque cortical areas and across primates and may represent a ubiquitous layer-based and frequency-based cortical mechanism.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

Through the monolithic integration of enhancement-mode n-type and p-type gallium nitride field-effect transistors, complementary integrated circuits including latch circuits and ring oscillators can be created for use in high-power and high-frequency applications.

Here, the authors compare gene expression signatures in rectal tissues of African green monkeys (AGMs) and rhesus macaques (RMs) acutely infected with simian immunodeficiency virus and find that AGMs rapidly activate and maintain evolutionarily conserved regenerative wound healing mechanisms.

Preclinical studies indicate that simultaneous HER2 and VEGF blockade may be beneficial in gastroesophageal adenocarcinoma (GEA). Here, the authors report the efficacy and biomarker analysis of a phase II clinical trial investigating the combination of bevacizumab (anti-VEGF) and standard-of-care CAPOX (capecitabine, oxaliplatin) and trastuzumab in previously untreated advanced HER2 + GEA.

Here, the authors characterize two distinct T_reg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2⁺ T_reg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3⁺ T_reg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Selective activation of the hepatoportal nerve plexus via peripheral focused ultrasound stimulation improves glucose homoeostasis and enhances glucose tolerance and utilization in rodent models of diabetes and in swine.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

Here, the authors design a microcavity-confined 2D heterojunction to realize the strong coupling among donor exciton, acceptor exciton, and cavity photon mode, leading to an unconventional energy transfer via polariton relaxation with an enhancement factor of ~440.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Bacterial cell division by cell wall synthesis proteins is guided by treadmilling filaments of the cytoskeleton protein FtsZ. Here authors use nanofabrication, advanced microscopy, and microfluidics to resolve the function of FtsZ treadmilling in the Gram-positive model organism Bacillus subtilis.

Soft tissue fabrication using digital light processing remains challenging. Here the authors present a molecular cleavage approach to achieve high-performance bioprinting of constructs with tissue-matching mechanical properties and structural complexity.

Lawsonite dehydration and release of oxidizing fluids could play an important role in sub-arc mantle oxidation in subduction zones, suggest measurements of changing oxygen fugacity in zoned garnets from Sifnos, Greece.

This protocol describes the working principle and implementation of axially swept light-sheet microscopy, which can image subcellular features at organ scales in 3D. It discusses how to optimize its design and provides a detailed guide for its construction and alignment.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

The in situ single-stranded open chromatin landscape is dynamically regulated in single cells. In their efforts to understand brain cells’ functional dynamics and to complement the other single-cell chromatin approaches, the authors present a method named CHEX-seq (CHromatin EXposed).

An integrated electro-optic isolator on thin-film lithium niobate enables non-reciprocal isolation by microwave-driven travelling-wave phase modulation. The isolator exhibits a maximum optical isolation of 48.0 dB at around 1,553 nm and an on-chip insertion loss of 0.5 dB.

Single-particle double-modulation absorption spectrometers based on whispering-gallery-mode microresonators achieve sub-100-Hz sensitivity to photothermal resonance shifts and allow for the study of arrays of Fano resonances in the context of plasmonic–photonic hybridization.

During the repair of double-stranded DNA breaks, cohesin mediates the extrusion of loops of DNA along which phosphorylated H2AX spreads to establish a repair zone.