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In a randomized phase 3 trial, neoadjuvant anti-PD-1 plus either paclitaxel and cisplatin or nab-paclitaxel and cisplatin elicited a significantly superior pathological complete response rate versus neoadjuvant paclitaxel and cisplatin alone in patients with resectable locally advanced esophageal squamous cell carcinoma.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a drug target for inflammatory bowel disease (IBD), impacting immune cell movement, but current treatments carry immunosuppression risks. Here, the authors show that a Gi-biased S1PR1 agonist, SAR247799, protects the endothelial barrier in IBD models without affecting immune cell egress, offering a potential new treatment strategy.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

Expanding the responsive dyes repertoire is currently a developing field in biorthogonal chemistry. In this article, the authors develop fluorophores that turn on their near-infrared fluorescence upon biorthogonal reaction based on a “torsion-induced disaggregation” approach, allowing for sensitive in vivo imaging of tumors.

The authors observe out-of-plane ferroelectric polarization induced by interlayer sliding in a multiferroic van der Waals semiconductor. The switching voltage scales down to 0.3 V at room temperature, which promises low-power device applications.

Atherosclerosis is associated with the dysregulation of lipid metabolism in vascular endothelial cells. Here, the authors show that the accumulation of lipid droplets in vascular endothelial cells disrupts endothelial ciliation and contributes to atherosclerosis by reducing cytosolic palmitic acid.

Cocaine is a tropane alkaloid produced by Erythroxylum novogranatense. Here the authors identify two polyketide synthases involved in cocaine biosynthesis and provide insight into the parallel evolution of these enzymes in tropane alkaloids-producing plants.

Bidirectional Mendelian randomization analyses in 3,432 Chinese individuals identify putative causal relationships between the gut microbiome and blood metabolite levels.

Designing an organic polymer photocatalyst for efficient hydrogen evolution in the near-infrared (NIR) light region is still a major challenge. The authors present here a series of polymer nanoparticles for a efficient hydrogen evolution under visible and NIR light irradiation, without combining or hybridizing with other materials.

A unified evolution-driven deep learning framework is presented, which outperforms state-of-the-art methods across various virus mutational driver predictions, and which captures fundamental patterns of virus evolution.

Delivering gene editing materials to the brain for glioblastoma therapy can boost the efficacy of chemotherapy. Here the authors reduce resistance to temozolomide using a reactive oxygen species-sensitive polymer-locking fusogenic liposome that can cross the blood–brain barrier and deliver short interfering RNA or CRISPR–Cas to glioblastoma with high specificity.

An improved watermelon reference genome and whole-genome resequencing of 414 cultivated and wild accessions provide insights into fruit quality traits and dessert watermelon evolution.

Metallic altermagnets are promising for applications due to the spin-polarized electric current that originates from their spin-split band structure. Now d-wave altermagnetism with antisymmetric spin polarization has been demonstrated in KV₂Se₂O.

Polar skyrmions are a topological polarization texture. While they have now been detected in numerous material systems, near universally these have required careful strain engineering. Here, Xue, Zhang, Zheng, Tong, Wang and coauthors observe polar skyrmions in the van der Waals ferroelectric CuInP2S6, without strain-engineering.

Here the authors developed a multi-phenotype imputation method termed PIXANT by leveraging efficient machine learning (ML)-based algorithms.

This study identifies PPKs as authentic protein kinases phosphorylating the far-red light photoreceptor phytochrome A and demonstrates that liquid–liquid phase separation of TZP promotes PPK-mediated phosphorylation of phytochrome A in far-red light.

A cryogenic electron microcopy study of structures of a human receptor for bitter taste finds that cholesterol can activate the receptor, while the tastant molecule acts allosterically on the receptor.

Ensembles of fear and extinction memories compete and interact to drive opposing behaviors. Here the authors identified insular cortical circuits as an executive gateway that decipher between fear and extinction memories via distinct subcortical pathways.

Using CO and H₂O to electrosynthesize oxygenates is a possible low-carbon synthetic route. Here, the authors study the CO adsorption behavior on Ag catalysts and design a Cu-Ag nanostructure catalyst with a relay mechanism that enhances the electrosynthesis of oxygenates.

Somatostatin receptor 2 (SSTR2) represents a therapeutic target of neuroendocrine tumors. Here, authors report two structures of SSTR2 bound to peptide octreotide and small molecule paltusotine, revealing the basis subtype selectivity and signal bias properties.

Genome sequencing and haplotype assembly of two cyprinid teleosts, a sexual tetraploid and an unisexual hexaploid, reveal insights into the evolutionary mechanisms underpinning the reproductive success of unisexual polyploid vertebrates.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulator of cell death pathways during embryogenesis and in infection/inflammation. Here authors show that tyrosine phosphorylation of RIPK1 by upstream kinases limits systemic inflammation and regulates haematopoietic homeostasis.

Propylene and propane have similar physicochemical properties, and thus their separation is challenging. Now, as an alternative to energy-intensive cryogenic distillation methods, a molecular sieving adsorbent with high propylene adsorption capacity has been shown to sieve propylene from propylene/propane mixtures to yield high-purity propylene.

The oxidation of sulfur dioxide to sulfate by hydrogen peroxide in aerosol water significantly impacts global continental regions. Abating oxidants can facilitate the benefit of sulfur dioxide reduction and positive feedback in sulfate mitigation.

Ultra-scaled transistors based on two-dimensional MoS₂ with physical gate lengths of 0.34 nm are reported, which show relatively good electrical characteristics and can be switched off.

Protein expression vectors in cell-free systems mainly rely on double-stranded DNA and single-stranded RNA. Here, authors use circular single-stranded DNA as a programmable vector for gene regulation in a cell-free expression system by identifying its expression pathways.

Low-frequency quasiperiodic oscillations in X-ray data are thought to trace the accretion flow in X-ray binaries. Here, the detection of 200 keV oscillations probes the innermost regions of MAXI J1820+070, revealing the precession of a small-scale jet.

An inhibitor of the SARS-CoV-2 main protease (Mpro), Y180, showed therapeutic efficacy against wild-type SARS-CoV-2 and its variants including Omicron after oral administration and improved survival in a humanized mouse model.

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.

Yang and colleagues have previously reported a clinically guided culture method to generate allogeneic CAR-NKT cells by engineering human hematopoietic stem and progenitor cells. As potential application, here the authors describe the design and characterization of allogeneic CD33-targeting CAR-NKT cells, showing anti-tumor activity in preclinical models of bone marrow-resident myeloid malignancies.

Achieving uniform coverage of interfacial layers in perovskite solar cells is challenging, especially over large areas. Li et al. present design guidelines to fabricate these layers with uniform morphology, suppressed defects and improved charge transport.

The V-shaped Challenger Deep in the Mariana Trench is the deepest part of the world’s oceans. Using 586 prokaryotic metagenome-assembled genomes and metatranscriptomic data, this study explores metabolic capabilities and activities of microorganisms involved in elemental cycling in hadal sediments, and reveals the different distribution of processes between its bottom-axis and slope.

This longitudinal study of young people with parents with bipolar disorder assessed genetic and symptomatic risks associated with brain surface features, identifying reduced baseline frontotemporal cortical thickness in individuals who developed mood disorders at follow-up.

piRNA processing factors and piRNA/PIWI complex are found in intermitochondrial cement (IMC) and chromatoid body (CB). Here, the authors show that piRNA loading orchestrates MIWI translocation from the IMC to CB, demonstrating its crucial role in spermatogenesis.

Vibronic coupling is a key feature of molecular electronic transitions, but its visualization in real space is an experimental challenge. Here the authors, using scanning tunneling microscopy induced luminescence, resolve the effect of vibronic coupling with different modes on the electron distributions in real space in a single pentacene molecule.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here the authors performed multi-omics analysis of human samples to investigate the mutational landscape of PSC and show three subgroups of PSC with distinct biology, prognosis and potential therapeutic strategies.

The severe volume expansion during the lithiation of micron-sized Si in Li-ion batteries requires a solid electrolyte interphase with reinforced mechanical stability. Here, the authors propose a solvent-induced selective dissolution strategy to regulate the mechanical properties of the interphase.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Hyperactivation of ribosome biogenesis (RiBi) causes excessive ribosome production, contributing to genome instability and cancer progression. The authors investigate the role of RiBPs in breast cancer, highlighting the upregulation of factors like DCAF13, which enhances cell proliferation by regulating Pol I transcription via K63-linked ubiquitination of RPA194.