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In a phase 1/2 trial in patients with advanced non-small-cell lung cancer (NSCLC), followed by a phase 2 trial in an EGFR-mutant selected population, treatment with the TROP2-targeting antibody–drug conjugate sacituzumab tirumotecan led to encouraging clinical response rates, especially in patients with EGFR-mutant NSCLC, which was supported by mechanistic data.

EB are conserved microtubule (MT) plus-end binding proteins. Here, Yang et al. report that Plasmodium EB1 possesses distinct MT-lattice affinity and decorates the full-length of spindle MTs. Gene deletion impairs the spindle-kinetochore lateral attachment, leading to anucleated male gametes.

Gastrointestinal stromal tumours (GISTs) are clinically heterogeneous, with varying degrees of aggressiveness. Here, the authors describe the genomic and transcriptomic landscape of 117 GISTs from 105 patients; they find four molecular subtypes as well as recurrent inactivating YLPM1 mutations in high-risk/metastatic GIST.

The rare lung cancer subtype pulmonary lymphoepithelioma-like carcinoma is linked to Epstein-Barr virus infection. Here, the authors provide a mutational landscape for this cancer, showing a low burden of somatic mutations and high prevalence of copy number variations.

Acidic CO₂ electroreduction suffers poor selectivity for multi-carbon products. Here, the authors report that lengthening the 2-position substituents of benzimidazole-based copper coordination polymer precatalysts retards H⁺ diffusion, reduces Cu-Cu coordination numbers, and promotes C-C coupling.

Tailed bacteriophages account for the majority of all phages. Here, the authors employ cryo-EM and structure prediction techniques to investigate the atomic structure of the R4C phage capsid and the in- situ structure of its unique long rigid tail.

Typically, Cu catalysts agglomerate under electrochemical conditions. Here, the authors report a coordination polymer catalyst with neighboring Cu sites which remain isolated and reduce CO₂ to C₂H₄ with high selectivity and stability

Using a chemical screening approach, Yang and colleagues identify PKC as a regulator of lysosome biogenesis, which controls the subcellular localization of TFEB and ZKSCAN3 through parallel signalling pathways and independently of mTORC1.

Understanding the structure-function relationship in Cu-catalyzed CO₂ reduction is challenging due to dynamic active sites. This study introduces stable coordination polymer catalysts with homogenized, single-site Cu, enabling the study and tuning of C–C coupling efficiency in CO₂ electroreduction.

Solid oxide ionic conductors typically require elevated temperature to activate ionic transport. Here the authors report unusually high proton conductivity close to room temperature in a hydrogenated oxide, HSrCoO_2.5, which they attribute to the intrinsically ordered oxygen vacancy channels and high proton concentration.

An interfacial co-assembly strategy for synthesizing gradient mesoporous hollow silica sheets is reported. The SO₄²⁻ and NH₄⁺ were aggregated by protonated amphiphilic polymer PVP and formed (NH₄)₂SO₄ crystals at the n-pentanol-water interface. Negatively charged silica oligomers can be confined on the (NH₄)₂SO₄ crystal surface by the Coulomb interaction of NH4⁺ and co-assembled with CTAB under the catalysis of ammonia molecules. After removing the (NH₄)₂SO₄ cores and CTAB template by washing and extraction, the first layer of mesoporous hollow silica was formed. Modulating the n-pentanol-water interface to n-hexane-water interface, n-hexane swelled CTAB micelle co-assembled with silica oligomers and formed the second layer of mesoporous silica with larger pore size. The finally obtained gradient mesoporous silica sheet shows remarkable gradient rejection rates for molecules with different sizes.

CO electroreduction is a promising carbonate-free approach to produce ethylene, but suffers from limited selectivity and low energy efficiency. By modifying copper with a strong electron acceptor, 7,7,8,8-tetracyanoquinodimethane, the water dissociation step is accelerated, leading to excellent ethylene selectivity and full-cell energy efficiency in CO electroreduction.

An East Asian winter monsoon proxy record using grain size variations in Chinese loess over the past 900,000 years shows that for up to 20,000 years after the interglacials at 400,000-year intervals, the weak monsoon winds maintain a mild, non-glacial climate at high northern latitudes.

Here the authors report that chromatin-associated RNAs (caRNAs) could play both cis and trans-regulatory roles in establishing cell-type-specific chromatin architecture by showing their capability to improve the prediction of genome folding.

Chlor-alkali process plays an important role in the chemical industry. However, large overpotential and low selectivity of currently used catalysts lead to high energy consumption. Here the authors report Ru-O₄ single site catalysts for chlorination evolution with 1000 h stability at 1000 mA cm⁻² in a seawater-like environment.

Two JmjC-domain-contain ing enzymes are shown to catalyse demethylation of histone H3K27me3, a histone modification mediated by polycomb proteins and associated with stem cell maintenance and differentiation.

It has been suggested that the magnetic properties of metal layers using reversible redox reactions could form the basis of memory devices but this requires fast electric control to be practical. Here the authors demonstrate this on sub-millisecond timescales in a metal–oxide heterostructure.

Materials are described here that can change their crystalline phase in response to the electrically controlled insertion or extraction of oxygen and hydrogen ions, giving rise to three distinct phases with different optical, electrical and magnetic properties.

Zhang et al characterise the mechanism by which GmBTB/POZ enhances resistance to P. sojae in soybean. They show that GmBTB/POZ directly associates with the heterochromatin protein GmLHP1 and mediates its degradation to regulate the salicylic acid signaling pathway, providing insights into the defence against a common soybean disease.

Histone lysine demethylases are chromatin modifiers that play important roles in many pathological processes such as inflammation and cancer, making them potentially attractive drug targets. In a recent study, Kruidenier et al. provided proof of concept by identifying chemical matters that inhibit demethylation mediated by the two related histone H3 lysine 27 demethylases, KDM6A and 6B (UTX and JMJD3). The KDM6 inhibitor shows remarkable substrate selectivity and can inhibit transcription of a plethora of pro-inflammatory genes in cell culture by altering H3K27me3 level at some of the KDM6 target genes.