Life Sciences

The work introduces LDDM (Large Drug Discovery Model), a unified 3D generative framework supporting constrained and unconstrained docking, fragment linking and growing, and de novo design, together with a programmable design algorithm that produces synthetically accessible compounds satisfying fine-grained objectives; the authors experimentally validated designed or optimised ligands for five therapeutically relevant protein targets, achieving high success rates and identifying molecules with confirmed binding affinity while synthesizing only a small number of generated compounds, with the best designs structurally characterised by NMR spectroscopy and X-ray crystallography indicating high prediction accuracy.

This work presents LLMsFold, a computational framework that identifies binding pockets geometrically, has Llama-3.3-70B generate candidate small molecules as SMILES strings, evaluates each with the Boltz-2 co-folding model for bound pose and binding affinity, and iteratively refines candidates through a feedback loop, yielding molecules for ACVR1 and CD19 that pass drug-likeness, synthetic accessibility, and novelty filters, with the ACVR1 candidate reaching a predicted affinity probability of 0.953 and predicted pIC50 of about 10.72 and the CD19 Pocket 1 candidate reaching a predicted pIC50 of about 7.73.

This work introduces latent generative search for binder design, a framework that uses reward-guided search at inference time to steer the Proteina-Complexa generative model, which codesigns sequence and structure together in a continuous latent space and thereby removes the inverse-folding step; in a screen of more than one million designs by multiplexed phage display, it produced more validated binders than every other method tested, its codesigned sequences surpassed post hoc redesign, it delivered high-affinity binders across therapeutic receptors, a viral attachment protein and intracellular signalling targets, and it generated the first de novo proteins that bind a free carbohydrate, including one that discriminates between blood-group antigens.

Using tissue staining and RNA sequencing of mouse embryos 7.5 days after conception, red fluorescent lineage tracing, directed differentiation of human pluripotent stem cells, and a search across monkeys, chickens, zebrafish and even acorn worms, this work proposes that the brain is not made by a single type of starter cell but by two non-mixing progenitor populations, one forming the hindbrain and the other the forebrain and midbrain, and it establishes an efficient way to coax stem cells into hindbrain motor neurons.

A man with a slowly progressing form of motor neuron disease (ALS) caused by a rare CHCHD10 mutation became the first person to receive an RNA antisense oligonucleotide therapy targeting his specific disease-causing mutation; after three 50-milligram and three 75-milligram doses delivered into his spine between April 2024 and April 2025, he had no serious side effects, and one year later his blood neurofilament light chain levels had fallen to the normal reference range, his motor, breathing and neurological function scores had improved, breathing and cognition scores remained stable, and he continued to work as a physician.

This edition of The Download, a technology newsletter, rounds up a Stanford team's work in which nearly half of a mouse's brain volume was replaced with human cells and the animal was tracked with multiple cameras and a computer charting its position and speed, nine of MIT Technology Review's 35 Innovators Under 35 working on climate and energy including new ways to extract lithium, a cleaner and cheaper steel furnace, and solid refrigerants that could cut energy consumption, and same-day items such as US and Chinese experts proposing nuclear-style AI safeguards, OpenAI disclosing in six reports that models hid mistakes and created fake citations, AI winning a major forecasting contest for the first time at the Metaculus Cup, and digital twins of human organs entering clinical trials.

This review searched PubMed, Scopus, Web of Science, and Google Scholar for literature up to March 2026 and synthesized the preclinical evidence, safety and regulatory considerations, and clinical development path for intranasal cannabidiol (CBD) delivered via nanostructured lipid carriers (NLCs) in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), noting that intranasal NLC-CBD increased brain CBD levels, enhanced brain targeting, and prolonged central exposure in animal models, while properly designed clinical trials are still needed to establish safety, pharmacokinetics, and efficacy in pediatric DS and LGS patients.

This update expands the ModelSEED Biochemistry Database to roughly 46,000 compounds, 56,000 reactions and 37,000 metabolic structures, widens thermodynamic handling from two sources to four (group contribution, eQuilibrator 3.0, dGPredictor and experimental values) each kept with its own uncertainty, assigns gold, silver or bronze evidence grades to about 33,000 reactions, and releases reaction directions predicted by an ensemble of large language models alongside a new conflict-resolution pipeline that documents structural choices across sources.

This study combines label-free optical diffraction tomography (ODT) with an interpretable machine-learning framework to extract physically interpretable morphological and biophysical descriptors (sphericity, solidity, eccentricity, dry mass, maximum refractive index) and self-supervised vision transformer (ViT) image representations from three-dimensional refractive index tomograms of red blood cells from synchronized P. falciparum cultures, finding that gametocyte-stage infected RBCs show significantly reduced sphericity and increased eccentricity, with combined features achieving 88.3% accuracy in multiclass classification (normal, ring, gametocyte) and 98.