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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.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

Hyperspectral reporter genes allow imaging of ground bacteria from aerial vehicles

Polyoxygenated aliphatic chains with multiple hydroxyl groups are common in a wide array of compounds, often with potent biological activity. Now, a new ruthenium catalyst enables selective dehydrogenation of a single hydroxyl group in a broad scope of complex polyols. This site-selective modification facilitates the rapid incorporation of nitrogen-based functional groups into diverse natural products.

Globally important BTEX hydrocarbons are separated using a T-shaped host with the shape and crystal tiling characteristics of a pentomino. A strategy based on designing and applying crystalline molecular ominos to perform separations of hydrocarbons and other environmentally-relevant compounds is outlined.

BioID detection of Ebola virus–host interactions when computationally integrated with existing host protein-protein networks, revealed functional cell protein complexes supporting infection, including the RNA decapping complex.

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but establish good ligandability of ATG8 isoforms through fragment screening and docking.

The trade-off between growth and production affects the application of engineered microbes. Here, the authors take the minimal cut set approach to predict metabolic reactions for elimination to couple metabolite production strongly with growth and achieve high production of indigoidine in Pseudomonas putida.

The collective synthesis of several oligomeric polypyrroloindoline natural products, including hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridines B and C, is accomplished through the iterative action of an asymmetric small molecule copper catalyst. This strategy also enables the synthesis of putatively unnatural quadrigemine H-type isomers.

Prenatal bisphenol A exposure is associated with an increased risk of ASD in boys through a mechanism involving aromatase suppression. These resulting ASD-related behaviors and brain abnormalities may be reversed through postnatal intervention with 10HDA in mice.

Dielectrics are essential for modern energy storage, but currently have limitations in energy density and thermal stability. Here, the authors discover dielectrics with 11 times the energy density of commercial alternatives at elevated temperatures.

The spatial segregation of distinct catalytic functionalities within the same material holds great promise for cascade or antagonistic reactions, but it remains challenging. Here, the authors report the successful realization of this approach for an efficient hierarchical porous silica catalyst featuring spatially separated sulfated zirconia and magnesium oxide.

JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—viain vitroselection from a vast library of cyclic peptides—that show selectivity over other KDMs.

Homogeneous Pt-group metal-based complexes make up the majority of C-H bond activation catalysts, but they are characterized by high cost and low abundance. Here, the authors report atomically dispersed titanium-aluminum-boron nanopowder for low-temperature catalytic activation of aliphatic C-H bonds via the element-specific cooperative mechanistic roles.

The cleavage of C–F bonds through hydrodefluorination is challenging and has been traditionally limited to unsaturated fluorocarbons. Now, a simple plasmonic approach based on the use of aluminium nanocrystal-supported palladium nanoparticles is introduced to effectively upgrade fluoromethane under visible light.

Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

A computational platform describing the spatial and temporal interactions of monomers during the formation of network polymers provides structure–property relationships that are used to synthesize 3D network polymers with tailored functionalities.

Directed evolution is a process of mutation and artificial selection to breed biomolecules with new or improved activity. Here the authors develop a directed evolution platform (PROTein Evolution Using Selection; PROTEUS) that enables the generation of proteins with enhanced or novel activities within a mammalian context.

Older people have suboptimal responses to primary series vaccines, which can place them at risk for adverse coronavirus disease 2019 outcomes. Here the authors show that booster vaccines provide a substantial increase in antibody levels in the short term but that there is significant waning 100 d after booster shots.

An inducer-free quorum-sensing circuit is applied to control endogenous bacterial gene expression and improve yields of a range of products.

A structure-guided fragment screen identified a compound, which interacts with a ligand-binding site of unknown function in eukaryotic initiation factor 4E (eIF4E). X-ray crystallography was used to characterise binding and target engagment was shown in cells.

The small cell size of bacteria is a key hurdle in studying condensates. To address this challenge, the authors develop an experimental framework to assess bacterial condensates based on how they form, dissolve, tune shape and size, and transition between material states.

Here the authors isolate monoclonal antibodies specific for Plasmodium vivax apical membrane antigen 1, and characterize the epitope of one antibody that inhibits invasion of reticulocytes and hepatocytes, and reduces liver infection in a mouse model.

How PDZD8 acted in Mitochondria-ER contact formation was unclear. Here, the authors show that binding to mitochondrial FKBP8 slows PDZD8’s rapid motion, enhancing contacts and mitochondrial complexity.

A triflimide-catalysed rearrangement of N-allylhydrazones has been developed that allows for the generation of a sigma bond between two unfunctionalized sp³ carbons such that no clear marker remains for how the bond was formed. This traceless bond construction offers new avenues for convergent fragment coupling in synthetic strategies.

Characterization of clinical isolates of the cryptic fungal pathogen Aspergillus latus revealed traits that distinguish it from other species. Steenwyck et al show that A. latus originated via allodiploid hybridization with both parental subgenomes actively expressed.

EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.

Biocompatible rare-earth nanoparticles with an emission maximum at 1,600 nm enable sensitive in vivo imaging.

Modification of the internal and external surface chemistry of microporous zeolite and metal–organic framework nanocrystals leads to a generalizable strategy to aqueous porous liquids and impart high gas-carrying capacities to liquid water.

The pseudopterosins are a family of natural products whose interesting anti-inflammatory and pain-relieving properties have inspired many synthetic approaches. Now, an unusual approach that starts with an axially chiral hydrocarbon that engages in a triple Diels–Alder sequence has been shown to result in the shortest total synthesis of a pseudopterosin so far.

The circadian rhythm generates out-of-equilibrium metabolite oscillations controlled by feedback loops under light/dark cycles. Now, it has been shown that these life-like properties can emerge from a non-equilibrium nanosystem comprising a binary population of enzyme-containing polymersomes capable of light-gated chemical communication, controllable feedback and coupling to macroscopic oscillations.

The Kondo effect usually refers to increased electrical resistance in metals due to spin-spin interactions between localized magnetic impurities and conduction electrons. Here the authors report a Kondo-like coupling between a light-induced exciton and localized impurity spins in Nd-doped hybrid perovskite.

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA-lipid nanoparticles while enabling high RNA expression.

Nitrous oxide is a potent atmospheric greenhouse gas that is thought to be produced in soils through biological processes. Field measurements reveal nitrous oxide fluxes near Don Juan Pond, Antarctica — of comparable magnitude to those found in tropical soils — which may result from abiotic water–rock reactions.

A single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products is described: this tandem diboration/cross-coupling reaction works on a broad range of substrates, requires small amounts of commercially available catalysts, and provides products in high yield and high selectivity.

Synthetic probiotic for a human metabolic disease is taken through a drug development pathway to enable translation into clinic trials.

Lipid droplet (LD) function relies on protein partitioning between the endoplasmic reticulum (ER) and LD. The authors show that UBXD8 adopts distinct conformations in both membranes and undergoes structural rearrangements during ER-to-LD partitioning.

Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.

MXenes are two-dimensional materials with diverse optoelectronic, biological, mechanical and chemical properties. This protocol describes how to prepare single-layer flakes of Ti₃C₂T_x, the most important and widely used MXene, from a Ti₃AlC₂ MAX phase precursor.

Programmable addition via site-specific targeting elements (PASTE) combines the specificity, efficiency and cargo size benefits of site-specific integrases with the programmability of prime editing for precise and efficient integration of large DNA sequences into mammalian genomes.

Here, the authors engineer microbial production of muscle titin fibers with highly desirable mechanical properties and provide structural analyses that explain the molecular mechanisms underlying high performance of this polymer with potential uses in biomedicine and textile industries, among others.

Application of pluripotent cells in regenerative medicine requires an understanding of how they exit pluripotency. Here the authors demonstrate support for the idea that pluripotency exit involves pluripotent intermediates that exhibit lineage bias by identifying and trapping a mesoderm biased sub-state in culture.

Kim and co-workers introduce a new ‘kinetic site deconvolution’ method to identify active sites on heterogeneous catalysts by linking reaction rates to specific adsorption environments.

The intermolecular amination of C–H bonds is an enabling transformation for the synthesis of nitrogen-containing molecules; however, developing catalysts for this class of reactions is very challenging. Now, an iron-based enzyme for this reaction has been engineered, demonstrating that a protein can confer a difficult new function upon an otherwise unreactive base metal.

QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

Macrocycles are well represented in natural product structures but have been challenging to access for inclusion in synthetic libraries. A new method uses ring expansion to convert fused small rings into macrolactones and macrolactams that occupy natural product–like chemical space.

Hydrogels, networks of water-swollen polymers, are being exploited for the local delivery of cells and biologically relevant molecules. Loebel et al. describe the preparation of supramolecular hydrogels and their characterization.