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Scalable single-cell total RNA sequencing unifies coding and noncoding transcriptomics

Nature Biotechnology, Published online: 31 March 2026; doi:10.1038/s41587-026-03068-6

Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.
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Mirror-enhanced 4Pi-SMLM with one objective enables isotropic nanoscale imaging

Nature Biotechnology, Published online: 31 March 2026; doi:10.1038/s41587-026-03083-7

Single-molecule 4Pi microscopy is simplified and made accessible by using a single objective.
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Massively parallel promoter mapping identifies edits to boost sorghum gene expression

Nature Biotechnology, Published online: 30 March 2026; doi:10.1038/s41587-026-03060-0

Non-transgenic crop improvement via cis-regulatory editing is limited by rare activating alleles and incomplete promoter maps. A massively parallel reporter assay in sorghum protoplasts quantifies more than 30,000 CRISPR-mimicking variants across three photosynthesis genes, finely mapping cis-regulatory modules and pinpointing compact edits that drive upregulated protein production.
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Engineering macrophage-targeted trispecific immune cell engagers for tumor immunotherapy

Nature Biotechnology, Published online: 30 March 2026; doi:10.1038/s41587-026-03104-5

Immune cell engagers (ICEs) have emerged as a promising strategy for cancer immunotherapy, but their efficacy in solid tumors remains limited, partly as a result of the difficulty of coordinating activating and inhibitory signals within the same immune cell. Here, we report a logic-gated cis-targeting strategy that enables ICEs to coordinate activating and inhibitory signals within macrophages, thereby enhancing tumor clearance in mouse models of solid cancers.
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Generalist biological artificial intelligence in modeling the language of life

Nature Biotechnology, Published online: 20 March 2026; doi:10.1038/s41587-026-03064-w

This Review discusses the promises and pitfalls of biological AI algorithms and presents a vision for generalist biological artificial intelligence, in which models can perform diverse tasks across biological domains.
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An engineered <i>E. coli</i> strain sustains intratumoral nitric oxide production to boost effectiveness of tumor immunotherapy

Nature Biotechnology, Published online: 18 March 2026; doi:10.1038/s41587-026-03055-x

An engineered Escherichia coli Nissle 1917 strain carrying a synthetic arginine–nitric oxide (NO) circuit enables sustained intratumoral NO production that promotes vascular normalization and immune reprogramming. This reshaped tumor microenvironment synergizes with blockade of the immune checkpoint PD-L1 to reinvigorate CD8+ T cells and drive durable tumor regression in mouse models.
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Sustained nitric oxide production by engineered <i>E. coli</i> remodels the tumor microenvironment and potentiates immunotherapy

Nature Biotechnology, Published online: 18 March 2026; doi:10.1038/s41587-026-03054-y

Solid tumors are sensitized to anti‑PD‑L1 immunotherapy by engineered E. coli to produce nitric oxide.
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Biomolecular profiling for noninvasive health monitoring

Nature Biotechnology, Published online: 12 March 2026; doi:10.1038/s41587-026-03050-2

Kim et al. present mass spectrometry and wearable sensor technology as complementary approaches that, when integrated, can co-evolve to open new possibilities for noninvasive health monitoring.
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