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Heterogeneity within clonal cell populations affects bioprocess engineering. Here, the authors report a biosensor-based toolkit to investigate phenotypic heterogeneity in engineered yeast, reveal pH-based subpopulations and metabolite production states, and modulate/shift subpopulation dynamics to increase lycopene production.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Researchers identify the cancer drug LY2090314 as a potent inhibitor of Toxoplasma gondii and Cryptosporidium and report the first crystal structure of the parasite kinase TgGSK3 bound to it, validating TgGSK3 as a therapeutic target.

The bacterial anti-phage toxin–antitoxin–chaperone defence system CmdTAC senses capsid proteins via CmdC, enabling dissociation from the CmdTAC complex of the RNA ADP-ribosyltransferase CmdT, which targets single-stranded RNAs, inhibiting viral replication.

Oxidative catalytic depolymerization of polystyrene (PS) can produce benzoic acid, but the annual consumption of benzoic acid is ~40 times lower than PS, so benzoic acid should be converted to higher-volume chemicals for the process to be viable. Here, the authors report a hybrid chemical and biological process that uses PS as feedstock for production of adipic acid, a high-volume co-monomer for nylon 6,6, via benzoic acid.

Muconic acid is a platform chemical with wide industrial applicability. Here, the authors report efficient muconate production from glucose and xylose by engineered Pseudomonas putida strain using adaptive laboratory evolution, metabolic modeling, and rational strain engineering strategies.

The catalytic performance of dilute Pd-in-Au alloys depends on the Pd ensemble size on the bimetallic nanoparticle surface. Here the authors reveal how Pd ensemble formation on Au nanoparticles depends on the deposition sequence and nanoparticle–support wetting interactions, consequently affecting reactivity.

The conversion of carbon dioxide to higher-value chemicals is an industrially important reaction. Here, the authors report a hybrid catalyst manganese oxide nanoparticle supported on mesoporous cobalt oxide, which catalyses the conversion of carbon dioxide to methanol at high yields.

Gene dosage-based expression upregulation suffers from instability and random gene integration. Here, the authors report HapAmp, a method that uses haploinsufficiency as evolutionary force to drive in vivo gene amplification, and demonstrate its applications in protein and biochemical production in yeast.

Using phenotypic screening followed by optimization of side activities, the authors here identify pyrazolopyrimidine phosphodiesterase (PDE) inhibitors as anti-cryptosporidial drug leads. Humanizing a Cryptosporidum PDE by CRISPR indicates they target the parasite enzyme.

The impact of ACKR3 constitutive activity is unknown. Here, the authors suppress basal ACKR3 activity using inverse agonistic nanobodies to stabilize an inactive conformation and revealing a role for ACKR3 in basal cell motility.

Laboratory automation, machine learning, and metabolic engineering may be combined to quickly and efficiently build productive microbial strains. Here the authors used these techniques in P. putida to boost isoprenol titers 5-fold over six DBTL cycles while sampling a reduced design space.

Targeting individual DNA secondary structures in the genome with small molecules is challenging. Here, the authors develop ATENA, a CRISPR-based platform for targeting specific DNA structures in cells with high precision, helping to elucidate their biological roles and guide therapeutic design.

Subtractive manufacturing of microstructures is important for many applications, yet photoresists for 3D laser lithography allow only removal after development under harsh cleavage conditions. Here, the authors introduce a set of chemoselective cleavable photoresists allowing the orthogonal cleavage of microstructures under mild conditions.

Gold has a vital role in human society and the global economy, but its production currently causes high levels of environmental pollution. This work reports an approach that can effectively produce gold from both primary and secondary resources without the use of toxic substances such as mercury or cyanide.

This protocol describes the synthesis of two photoredox catalysts, [Ir{dF(CF₃)₂ppy}₂(bpy)]PF₆ and [Ru(bpy)₃](PF₆)₂, that are activated by visible light. These single-electron transfer agents are used to facilitate diverse synthetic transformations.

Medium- and branched-chain diols and amino alcohols are important industrial feedstocks, but they are biosynthetically challenging to produce. Here the authors introduce a modular polyketide synthase platform for the efficient production of these compounds.

Development of comprehensive structure–activity relationships for coronatine has been a major goal in the agrochemical industry. Here, the authors report the gram-scale production and structure–activity relationship of parent coronafacic acid and ultimately rationalise the biological activity of analogues of this phytotoxin.

Authors investigate quasi-2D nanoscale emitters on different substrates with tapping mode tip-enhanced spectroscopy. They visualize in-plane near-field and radiative energy propagation via Surface plasmon polaritons launched by the nanoscale emitters on dielectric/Au or SiO₂/Si substrates.

Atomic-resolution microscopy and AI reveal how metallic nanowires grow inside carbon nanotubes through atom-by-atom wetting, advancing understanding of how next-generation materials can be synthesized from the atomic scale up.

MetaGraph enables scalable indexing of large sets of DNA, RNA or protein sequences using annotated de Bruijn graphs.

Net-zero bioplastics are possible when combined with high recycling rates. This study presents a mixed polyester recycling process integrated with monomer separation and purification for both fossil- and bio-based plastics. Techno-economic and life cycle analyses confirm its environmental and commercial advantages, advancing the path toward circular, low-emission polyester plastics.

Spatially resolved transcriptomic, metabolomic and proteomic analyses of human liver samples highlight the role of lipid-associated macrophages in metabolic dysfunction-associated steatotic liver disease.

The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.

The cryo-EM structure of the herpes simplex virus helicase–primase (HP) complex informs about the mechanism of action of HP inhibitors pritelivir and amenamevir, which are drugs of clinical relevance.

We provide two procedures to cover distinct approaches for the initiation of lymph node metastases in mice: one for studying the metastatic cascade in tumorigenic cells and the other for studying the effect of metastatic formations in the host.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

By developing a functional nuclear import system and correlative imaging workflow, this study reveals that HIV-1 nuclear entry relies on the elasticity of both the viral capsid and the nuclear pore to enable the selective passage of small HIV-1 cores.

Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in adolescence.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

Liquid crystals (LC) are promising materials for the fabrication of reconfigurable arrays of 2D nanomaterials but it remains difficult to achieve stable dispersions of nanomaterials. Here, the authors report on good dispersions of pristine CdSe nanoplatelets (NPLs) in LCs, and reversible, rapid control of their alignment and associated anisotropic photoluminescence using a magnetic field.

Inflammation promotes insulin resistance in adipocytes, but the mechanism is unclear. Here, the authors show that the inflammatory transcription factor IRF3 drives expression of AIG1, which encodes a hydrolase that breaks down a class of insulin-sensitizing lipid called FAHFAs.

There is an unmet clinical need for a rapid point-of-care tests to identify patients at high-risk of developing acute liver failure following a paracetamol overdose. Here, authors assess a diagnostic test, consisting of a lateral flow immunoassay paired with a handheld Raman reader, in performance evaluation studies.

Distinguishing biotic compounds from abiotic ones is critical to the search for life in the universe. Here, the authors demonstrate that the abiotic ethane has distinctively low 13C-13C abundances compared to biotic ethane.

Human host-associated cellular products may act as induction agents for bacteriophages.

The synthetic biology era has seen a rapidly growing number of engineered DNA sequences. Here, the authors develop a deep learning method to predict the lab-of-origin of a DNA sequence based on hidden design signatures.

Synthetic materials tend to excel in either stiffness or extensibility, whereas a combination of the two is necessary to exceed the performance of natural biomaterials. Here the authors present a bioinspired polymer consisting of cyclic β-peptide rings that is capable of transitioning between rigid and unfolded conformations on demand.

The development of highly effective Earth-abundant catalysts for C(sp²)-N cross-coupling represents an on-going challenge in synthetic chemistry. Here, the authors report a nickel complex containing a bisphosphine ancillary ligand allowing room-temperature couplings of amines and ammonia with a range of electrophiles.

Understanding the dynamics of how drug resistance originates in cancer remains crucial, but it is not possible to observe them directly. Here, the authors construct a mathematical framework to infer drug resistance dynamics in cancer using lineage tracing and population size data, which is confirmed with experimental evidence and single-cell sequencing.

Systematic discovery of proteins interacting with low-abundance RNAs is challenging. Here, the authors develop an enhanced HyPro technology to identify proteins associated with compact RNA compartments and single RNA molecules, revealing early defects in ALS-linked mutant C9orf72 transcripts.

Jarrett Eshima and colleagues report a tool named Biodome which can aid in the recovery of volatile organic compounds from cell cultures. Their method enables the sampling of complex biological matrices and identification of volatile metabolites.

Many properties of polymers are dictated by topology. However, the topology of a macromolecule is typically a static feature after synthesis. Now, an approach to dynamic and transformable macromolecular architecture has been developed. When triggered by an external stimulus, macromolecular topology can be triggered to transform via thermodynamic control.

Different types of SETBP1 variants cause variable developmental syndromes with only partial clinical and functional overlaps. Here, the authors report that SETBP1 variants outside the degron region impair DNA-binding, transcription, and neuronal differentiation capacity and morphologies.

Axons have always been assumed to be cylindrical. Using in silico modeling and cryopreservation of tissues, Griswold et al. demonstrate that unmyelinated axons of the mammalian central nervous system exhibit pearls-on-a-string morphology through their entire length.

Here the authors show that BTLA on effector T cells interacts with HVEM on other immunosuppressive cells in the tumor microenvironment. The authors also present evidence that overcoming this checkpoint can ehance CAR T functionality.

Substitutional atomic doping is a process by which atomic defects are introduced into a host material, altering its properties; substitutional doping of cadmium selenide or lead selenide nanocrystal lattices with gold nanocrystals has now been achieved, the key being to ensure that the dopant nanocrystals are similar in size to the host nanocrystals.