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The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

It is shown that mice lacking the renal Rhcg factor have impaired ammonium excretion, thereby refuting the long-standing notion that rapid transepithelial transport of non-ionic ammonia occurs solely by lipid phase diffusion. In addition, it is shown that Rhcg is required for epididymal fluid homeostasis with clear consequences for male fertility.

In a non-prespecified interim analysis of a phase 1 trial, autologous PRAME-directed TCR T cell therapy was safe and elicited durable responses in patients with recurrent and/or treatment-refractory PRAME⁺ advanced solid tumors, including melanoma and synovial sarcoma.

Machine learning models represent an opportunity for the automatic generation of histopathology reports. Here, the authors develop HistoGPT, a vision language model that can generate reports from multiple gigapixel-sized whole slide images and also predict tumour thickness, subtypes, and margins, among other diseases.

Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.

Chemical biology is well defined at its core—chemistry helping to answer biological questions—yet the boundaries are rather fuzzy. What are the differences between chemical biology and pharmacology? Is intracellular imaging a branch of chemical biology, and what about screening libraries? At Chemical Biology 2008, held in Heidelberg in October, participants heard presentations covering all these topics and more.

The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking Aβ fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

GEMIN5, an RNA-binding protein, is required for formation of small nuclear ribonucleoproteins. Here, the authors identify loss of function mutations in GEMIN5 that are associated with a human neurodevelopmental disorder.

This article presents NAPstars, a family of genetically-encoded biosensors that enable real-time monitoring of NADP redox dynamics across species. The sensors reveal robust NADP redox regulation, cell-cycle-linked NADP oscillations, and glutathione as the major conduit for anti-oxidative electron flux.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

A robust acoustic droplet ejection–drop-on-tape method delivers samples to an X-ray free-electron laser source for combined serial femtosecond crystallography and X-ray emission spectroscopy analysis, providing detailed insights into macromolecular reaction dynamics.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

The electronic transport properties of charge-ordered kagome metals are controversial. Now careful measurements on unperturbed samples show that previously measured anisotropy in the transport occurs only when external perturbations are present.

Cas9-specific antibodies and reactive T cells are found in the majority of healthy adult human serum samples analyzed. Such preexisting adaptive immunity should be taken into consideration as the CRISPR–Cas9 system moves toward clinical trials.

In the ongoing phase 1/2 BNT211-01 trial, CLDN6-specific chimeric antigen receptor (CAR)-T cells given with or without CARVac, a CAR-T cell-amplifying RNA vaccine, were well-tolerated and exhibited encouraging clinical activity in patients with relapsed or refractory CLDN6-positive solid tumors, with the highest response rate in patients with germ cell tumors.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

γδ T cells are unique T lymphocytes with cytotoxic functions, targeting infections and tumours. Here authors show that the target killing function of γδ T cells is tightly regulated at the level of the availability of lytic molecules granzyme B and perforin.

Understanding how N₂ fixation is distributed in aquatic systems is key to enabling robust N-budgets. In a model ecosystem, Ehrenfels et al. find that the hydrodynamic regimes (stratification/upwelling) play a critical role in modulating N₂ fixation.

Greater emphasis on reproducibility and reusability will advance computational pathology quickly and sustainably, ultimately optimizing clinical workflows and benefiting patient health.

The study compares acclimatization protocols for metabolic cages and found that the standard housing at 23 °C impacts mice’s physiology and welfare owing to cold stress. However, thermoneutral housing provides a simple solution to improve mouse welfare.

A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

Enigmatic blooms of phytoplankton in aquatic oxygen-deficient zones could exacerbate depletion of nitrogen. Here the authors perform stable isotope experiments on the oxygen-deficient waters of Lake Tanganyika in Africa, finding that blooms drive down fixed nitrogen and could expand as a result of climate change.

The prevalence of cognitive dysfunction among people with chronic kidney disease (CKD) is disproportionately high compared with that in the general population. This Review examines current evidence on key drivers of cognitive impairment in people with CKD, and highlights gaps in knowledge and potential therapeutic targets.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

Clostridium difficile CDT toxin suppresses protective host eosinophilic responses through TLR2 signalling to induce inflammation.

Inflamed tissue has a special milieu, with hypoxia, high levels of metabolites from anaerobic glycolysis, and acidosis. Stimulation of a proton-activated receptor, TDAG8 (GPR65), in T cells has an important role in inflammatory bowel disease by balancing pro- and anti-inflammatory signals.