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Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis

Metagenomic analysis reveals how multiple stressors disrupt virus–host interactions in multi-trophic freshwater mesocosms

Margaret Boden obituary: cognitive scientist who explored how machines might emulate human imagination

Decoding technical multi-promoted ammonia synthesis catalysts

Abstract Ammonia is industrially produced by the Haber-Bosch process over a fused, multi-promoted iron-based catalyst. Current knowledge about the reaction has been derived from model systems of reduced structural complexity, impeding any clear-cut structure-activity correlation relevant for the industrial counterpart. Here, we unveil the structural evolution of complex, technical, multi-promoted ammonia synthesis catalysts by operando scanning electron microscopy and near-ambient pressure X-ray photoelectron spectroscopy. We highlight that the activation is the critical step in which the catalyst is formed and decode the pivotal role of the promoters. We discover that the active structure consists of a nanodispersion of Fe covered by mobile K-containing adsorbates, so called “ammonia K”. The porous catalyst is stabilized by mineral cementitious phases containing oxides of Al, Si, Ca, and Fe. The synergism between the different promoters contributes simultaneously to the structural stability, hierarchical architecture, catalytic activity, and poisoning resistance. The confluence of these aspects is the key for the superior performance of technical catalyst formulations.

Structures and mechanisms of U6 snRNA m6A modification by METTL16

The bispecific innate cell engager AFM28 eliminates CD123+ leukemic stem and progenitor cells in AML and MDS

Abstract Strategies targeting leukemic stem and progenitor cells (LSPCs) are needed for durable remissions in acute myeloid leukemia (AML) and high-risk myelodysplastic neoplasms (MDS). While CD123 constitutes a promising target on LSPCs and leukemic blasts, previous CD123-targeting approaches showed limited efficacy and challenging safety profiles. Here, we describe the preclinical efficacy and safety of the bispecific CD123/CD16A innate cell engager “AFM28”, demonstrating superior activity against AML and MDS patient-derived LSPCs and blasts in vitro compared to an Fc-enhanced CD123-targeting antibody, especially towards CD123low and/or CD64+ leukemic cells. AFM28 induces autologous anti-leukemic activity in fresh AML whole blood cultures, demonstrating its potential to enhance NK cell function from AML patients. Responsiveness can be further enhanced by allogeneic NK cell addition. Anti-leukemic activity of AFM28 is confirmed in xenograft mouse models. In addition, AFM28 is well tolerated and demonstrates pharmacodynamic activity in cynomolgus monkeys. Altogether, our results indicate that AFM28 has the potential to reduce relapse-inducing residual disease and promote long-term remissions for patients with AML and MDS with a favorable safety profile.

Highly scalable prefusion-stabilized RSV F vaccine with enhanced immunogenicity and robust protection

Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma

Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women

Abstract Breast cancer (BC) is one of the most common cancers globally. Genetic testing facilitates screening and informs targeted risk-reduction and treatments. However, genes included in testing panels are from European-ancestry studies. We conducted a pooled case-control analysis in self-identified Hispanic/Latina women (4178 cases and 4344 controls), using whole exome sequencing and a targeted panel. We tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. Using logistic regression, we found a strong association of LoF variants in FANCM with ER-negative BC (p = 4.1 × 10− 7), odds ratio [confidence interval]: 6.7 [2.9–15.6]). Among known susceptibility genes, BRCA1, BRCA2, and PALB2 strongly associated with BC. FANCM was previously proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested clinically. Our results demonstrate that FANCM should be added to BC gene panels.

Internally hollow Cu2O nanoframes with the abundance of {110} facets enhance direct propylene epoxidation

Redefining Lung Cancer Therapy — A Long-Awaited Shift in Strategy

Novel environment exposure drives temporally defined and region-specific chromatin accessibility and gene expression changes in the hippocampus

Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

CO-promoted polyethylene hydrogenolysis with renewable formic acid as hydrogen donor

AAV Gene Therapy in Severe Hemophilia B

Swift bricks, ancient tattoos and more: Books in brief

Integrating artificial intelligence and optogenetics for Parkinson’s disease diagnosis and therapeutics in male mice

Abstract Parkinson’s disease (PD), a progressive neurodegenerative disorder, presents complex motor symptoms and lacks effective disease-modifying treatments. Here we show that integrating artificial intelligence (AI) with optogenetic intervention, termed optoRET, modulating c-RET (REarranged during Transfection) signalling, enables task-independent behavioural assessments and therapeutic benefits in freely moving male AAV-hA53T mice. Utilising a 3D pose estimation technique, we developed tree-based AI models that detect PD severity cohorts earlier and with higher accuracy than conventional methods. Employing an explainable AI technique, we identified a comprehensive array of PD behavioural markers, encompassing gait and spectro-temporal features. Moreover, our AI-driven analysis highlights that optoRET effectively alleviates PD progression by improving limb coordination and locomotion and reducing chest tremor. Our study demonstrates the synergy of integrating AI and optogenetic techniques to provide an efficient diagnostic method with extensive behavioural evaluations and sets the stage for an innovative treatment strategy for PD.

Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis

Trump order gives political appointees vast powers over research grants

Catalytic cooperation between Ru and Pd atoms on hierarchical porous Ce-based oxide for boosting engine exhaust purification