Using electron microscopy, scientists mapped a Caenorhabditis elegans nervous system and Drosophila brain at single-neuron resolution. Connectomics work on bigger brains takes new methods strategies.

A newly proposed explanation for the slipperiness of ice has revived a centuries-long debate.

A fired public-health official, a mosquito breeder and a baby with a smile seen around the world. These are just a few of the remarkable people chosen for Nature’s 10.

The rapid and economical synthesis of novel bioactive compounds remains a hurdle in drug discovery efforts. This study demonstrates an integrated medicinal chemistry workflow that effectively diversifies hit and lead structures, enabling an acceleration of the critical hit-to-lead optimization phase. Employing high-throughput experimentation (HTE), we generated a comprehensive data set encompassing 13,490 novel Minisci-type C-H alkylation reactions. These data served as the foundation for training deep graph neural networks to accurately predict reaction outcomes. Scaffold-based enumeration of potential Minisci reaction products, starting from moderate inhibitors of monoacylglycerol lipase (MAGL), yielded a virtual library containing 26,375 molecules. This virtual chemical library was evaluated using reaction prediction, physicochemical property assessment, and structure-based scoring, identifying 212 MAGL inhibitor candidates. Of these, 14 compounds were synthesized and exhibited subn

In vivo experiments and clinical cohort analyses show that hypoxia-inducible factor 2 (HIF2)-induced parathyroid hormone-related protein (PTHrP) expression contributes to cachexia in the context of renal cell carcinoma (RCC). The pathway can be targeted by HIF2 inhibitors, including belzutifan, which may reduce cachexia in patients with RCC.

Immunotherapy reshapes the interaction between the tumor microenvironment and cancer stem cells. In this issue of Cancer Cell, Guo et al. revealed that SOX2High tumor-initiating stem cells reprogram neutrophils that block interferon-induced reprogramming after immunotherapy, maintaining their pro-tumor phenotype at the tumor-stroma interface.

Guo et al. show that anti-PD-L1 + CD40 agonist therapy activates anti-tumor functions in neutrophils within the tumor stroma. Conversely, SOX2High tumor-initiating stem cells at the tumor-stroma interface suppress interferon responses and maintain immunosuppressive functions of neutrophils via the arachidonic acid-prostaglandin E2 axis, forming a protective niche.

Whole-genome and transcriptome analysis of 1,364 cases of breast cancer from South Korea broadens our understanding of breast cancer biology and reveals genomic features that connect tumour biology with treatment responses and clinical outcomes.

Randomly acquired mutations face strong negative selection, except on certain cancer-promoting backgrounds.

Bibliophile Andrew Robinson reveals 10 essential science reads from the past year.

ALT: a christmas card that says joyeux st nicolas on the top

Today, medical research builds up an understanding of the whole from molecular parts, but artificial intelligence can revive an approach building down from patient-level data to theory and understa...