Skip to content

#方法/工具

Today 0 items
Oct 15Thu
  1. biorxiv.org49

    Pervasive expression of early embryonic programs in cancer has stage-dependent survival impact

    Early embryonic gene expression programs are widespread in human tumours, and transcriptional similarity to distinct preimplantation stages independently predicts overall survival beyond age, sex, mutational status and molecular subtype. Similarity to zygote and 2-cell embryo stages predicted improved survival, driven in kidney cancer by stromal and immune cells, while trophectoderm-associated programs in tumour cells predicted worse survival in breast cancer and melanoma and were linked to MYBL2 and FOXM1 dependencies.

  2. biorxiv.org42

    Spatial Tumour Tissue Distribution Dynamics of a Bicycle Peptide-MMAE Toxin Conjugate Profiled by Targeted Mass Spectrometry

    Laser capture microdissection coupled to targeted LC-PRM mass spectrometry maps the spatial distribution of MMAE released from the NECTIN-4-binding Bicycle Drug Conjugate zelenectide pevedotin (BT8009) at sub-tissue resolution in mice. The method showed progressive accumulation and sustained retention of MMAE in tumour tissues over 24 h, while levels in plasma, liver and muscle declined after early exposure, and revealed heterogeneous MMAE distribution between tumour cell-rich and stroma-rich regions with distinct temporal patterns.

  3. nature.com71

    Artificial intelligence-enabled clinical phenotyping of human brown fat

    AI-enabled quantification of brown adipose tissue (BAT) activity in humans links higher BAT activity to a healthier metabolic profile and lower rates of psychiatric disease. The same approach identified existing pharmacologic agents that could be repurposed to activate BAT in humans. The work provides a scalable way to phenotype BAT and connect it to clinical outcomes and drug targets.

    Why it matters: It shows AI-based BAT phenotyping at scale, linking brown fat to metabolic and psychiatric outcomes and to repurposable drugs.

  4. nature.com80

    Modelling mouse embryogenesis from chemically induced totipotent stem cells

    A mouse embryo model built from chemically induced totipotent-like stem cells progresses through key developmental milestones, including gastrulation, embryonic axis formation, haematopoiesis and early organogenesis. The work extends embryo modelling to a starting cell type with totipotent-like properties. It provides a system for studying development from the earliest stages onward.

    Why it matters: It shows totipotent-like stem cells can generate an embryo model reaching organogenesis.

Oct 14Wed
  1. biorxiv.org45

    A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors

    A tiered precision oncology framework combining deep whole-genome sequencing, single-cell RNA sequencing, and ex vivo functional drug screening was applied to 17 children with malignant CNS tumors. Functional screening gave every patient at least one high-confidence targeted-therapy or chemotherapy nomination, single-cell RNA sequencing found an average of 37 druggable gene targets per patient, and high-confidence targeted-therapy recommendations rose fourfold. Functional classifications matched outcomes in 8 of 10 evaluable cases.

  2. biorxiv.org40

    Predicting resistance to synthetic lethal therapies in cancer

    Resistance to synthetic lethal cancer therapies can be predicted from molecular network features. A random forest model combining protein-protein interaction, co-expression and essentiality data, trained on CRISPR-Cas9 resistance screens across ten SL biomarker-target pairs, achieved a mean AUROC of 0.72 under leave-one-SL-pair-out validation (range 0.57-0.91) and independently predicted resistance to the MTAP-PRMT5 and ATM-ATR therapies now in trials. The work gives a computational way to anticipate resistance mechanisms before they emerge.

Oct 11Sun
  1. Sci Adv66

    Contagion-preserving compression for multiscale epidemic modeling.

    Iterative structural coarse-graining (ISCG) compresses large networks into multiscale representations that preserve contagion dynamics. In the saturation regime the compressed networks reproduce outbreak sizes, node-level infection risks, and spatiotemporal infection trajectories. Interventions designed on these representations, including influence maximization, immunization, and surveillance, consistently outperform adaptive centrality-based methods.

    Why it matters: Offers a compression method that preserves contagion dynamics and improves intervention design on large networks.

Oct 9Fri
  1. biorxiv.org41

    Mathematical Modelling of Stochastic Gene Expression Quantifies mRNA Heterogeneity in Cancer Cell Populations with Extrachromosomal DNA

    A stochastic model of gene transcription quantifies mRNA production and decay in cancer cells carrying ecDNA, exploring the space of mRNA distributions possible from a given ecDNA distribution. Applied to single-cell measurements of ecDNA and mRNA counts in cell lines, it estimates transcriptional parameters that are strikingly similar across cell lines and amplification types. Simulating genotoxic therapy, the model predicts the mRNA composition of persisting cells, linking ecDNA-driven heterogeneity to treatment resistance.

  2. doi.org40

    Innovative niosome screening for efficient gene delivery in senescent primary umbilical cord stroma-derived MSCs

    DP20CQ niosomes, built with DOTMA and polysorbate 20 plus chloroquine, delivered genes more effectively than DP80CH formulations in Palbociclib-induced senescent UC-MSCs from four donors. At DOTMA/DNA ratios of 10/1 and 15/1, DP20CQ achieved the highest transgene expression in senescent UC-MSCs, surpassing Lipofectamine, with strong endosomal escape at 10/1 and no loss of cell viability. This positions niosomes as gene delivery vehicles for senescent cells in antiaging therapy.

Oct 6Tue
  1. biorxiv.org51

    A near-ubiquitous plasmid characterises Second Pandemic Yersinia pestis

    A cryptic 34 kb plasmid, pTP33, is present in almost all Second Pandemic Yersinia pestis strains and undetectable in all other ancient strains, revealed by variation-graph pan-genomics of 110 new and 12 published ancient plague genomes. pTP33 is a phage-plasmid-like element with homologues in insect-associated Enterobacterales, suggesting it widened vector range beyond the rat/flea cycle and helps explain the Second Pandemic's far higher mortality, up to 60% of Europe's population in the Black Death, versus the Third Pandemic.

  2. nature.com65

    Decoding systemic vascular health and hypertensive disorders in pregnancy through retinal imaging and Visionary AI

    Hypertensive disorders of pregnancy affect 2–15% of pregnancies and are usually diagnosed after 20 weeks of gestation, once hypertension, proteinuria or organ dysfunction appear, even though low-dose aspirin started before 16 weeks can reduce risk of preterm delivery with preeclampsia by up to 62%. The paper develops retinal imaging with AI to detect the systemic and placental vascular changes that precede symptoms, building on evidence that women with preeclampsia show retinal arteriolar narrowing, increased tortuosity and reduced capillary density before diagnosis.

    Why it matters: It tests a noninvasive retinal imaging route to early preeclampsia risk identification, which current late diagnostics fail to provide.

  3. biorxiv.org47

    The mammalian genome is punctuated by regularly spaced nucleosome islands

    A deep-learning model trained on genome-wide nucleosome maps from mouse embryonic stem cells predicts nucleosome occupancy from primary DNA sequence alone and separates shared biological signal from assay-specific noise. In silico mutagenesis pinpointed positioning regions built from short 5-to-20-base-pair motifs in dense regulatory windows, with CCCTC-binding factor motifs in SINEs, zinc-finger-bound motifs in LINEs, and microsatellite repeats acting as potent organizers of nucleosome phasing. This extends sequence-encoded nucleosome architecture, known in yeast, to mammalian genomes.

Oct 5Mon
  1. Sci Adv68

    Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies.

    An encapsulated cell-based "biologics factory" using an immunomodulatory alginate formulation sustained stable serum titers of the HIV-neutralizing mAb 3BNC117 for 1 year in immunocompetent mice, supported by an anti-inflammatory, proresolving immune niche that attenuates fibrosis. The platform produced 13 diverse mAbs from an allogeneic cell chassis, and in a nonhuman primate subcutaneous implant maintained stable ipilimumab titers for more than 6 months with no detectable toxicity, antidrug antibodies, or adverse events across a three-dose escalation. A retrievable macrodevice allows on-demand termination and dose-proportional tuning, pointing toward replacing frequent injections with single-administration therapy.

    Why it matters: It shows a single implant can deliver monoclonal antibodies for months to a year, replacing repeated injections.

Sep 29Tue
Sep 28Mon
  1. nature.com42

    Accelerated discovery of thermostable mRNA–lipid nanoparticle vaccines using data-efficient AI

    The paper presents a data-efficient AI workflow, Bayesian optimization implemented in the AutODEx framework, for accelerating the discovery of thermostable mRNA-lipid nanoparticle vaccines. Candidate formulations were optimized toward stability, using a SARS-CoV-2 RBD sequence deposited at GenBank (OP839194). Datasets and source code are publicly released on Zenodo and GitHub.

    Why it matters: It shows an AI-driven route to thermostable mRNA-LNP vaccines, a known cold-chain bottleneck.

  3. nature.com45

    Cargo size matters when designing lipid nanoparticles for delivery of large gene editors

    Ionizable lipids screened with a gene-editor-sized messenger RNA yielded LC-1, a lipid that forms nanoparticles with a structure enhancing endosomal escape. LC-1 enabled efficient genome editing in the liver, lung and brain of mice, addressing the reduced performance lipid nanoparticles often show when carrying the large messenger RNAs that encode gene editors.

Sep 25Fri
Sep 23Wed
  1. nature.com42

    Chiral oxazolidinones via biocatalytic aziridination of unactivated alkenes

    Engineered haemproteins catalyse an aziridination and ring-expansion cascade that converts simple unactivated alkenes directly into enantioselective chiral oxazolidinones, including 5-(S)-aminomethyl oxazolidinone scaffolds used in next-generation antibiotics against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. The work extends haemprotein nitrene transfer beyond conjugated systems such as styrenes to unactivated alkenes, and computational analysis shows that mutations introduced by directed evolution control the enantioselectivity.

Sep 22Tue
  1. Nature Medicine52

    Large-scale esophageal cancer screening through noncontrast computed tomography and artificial intelligence

    Esophageal cancer detection through noncontrast computed tomography is enhanced by a new artificial intelligence tool called Esophageal AI-Guided malignant Lesion Evaluation. In a large-scale study, the tool achieved high sensitivity and specificity across diverse settings.

    Why it matters: It points to CT-based AI screening as a route to wider esophageal cancer detection.

Sep 18Fri
  1. nature.com47

    A universal visual foundation model for computational cytopathology

    CROWN is a universal visual foundation model for computational cytopathology, benchmarked on more than 200 real-world cytology tasks across cohorts, including lymph node metastasis and cervical screening datasets. It gives cytopathology a single pretrained model that can be evaluated across many clinical cytology settings rather than task-specific systems.

    Why it matters: A single foundation model covering over 200 real-world cytology tasks could standardize computational cytopathology workflows.

Sep 17Thu
  1. Nature58

    Developmental xenocortication using human-derived organoids in mice.

    A transplantation platform generates xenocortical mice by genetically depleting glutamatergic neurons from mouse neocortex and hippocampus, then neonatally engrafting the cortical cavity with human stem-cell-derived cortical organoids. The organoids occupy most of the cortical volume, yield diverse human cortical cell types including layer 5 extratelencephalic projection neurons, and integrate with the mouse nervous system, showing organized activity resembling developing circuits. Host mice retain broadly preserved locomotion with selective differences in limb coordination, and the platform yields behavioural readouts in an injury model of developing human cortical cells.

    Why it matters: It provides circuit- and behaviour-level readouts from integrated human cortical neurons in living mice, enabling disease modelling and therapy testing.

Sep 16Wed
  1. Nat Biotechnol44

    A versatile nanopore identifies four classes of analytes simultaneously.

    A nanopore sensor built by modifying a bacterial porin identifies amino acids, nucleoside monophosphates, saccharides and peptides simultaneously, with 98.7% classification accuracy when coupled with machine learning. The platform also enables compositional analysis of native glycopeptides, extending nanopore detection beyond a single analyte class.

    Why it matters: Single sensor platform covers four analyte classes at once, including native glycopeptide analysis.

  2. Nature54

    Breaking timescales with generative sampling of conformational transitions.

    Gen-COMPAS, a generative committor-guided path-sampling framework, reconstructs biomolecular transition pathways without predefined collective variables and at acceptable computational cost. It combines a denoising diffusion probabilistic model producing structurally plausible intermediate targets with committor-based filtering, yielding transition-region ensembles at nanosecond-to-submicrosecond scales where conventional approaches need orders of magnitude more sampling. Applied to systems from a miniprotein to a pentameric ligand-gated ion channel, it recovers committors, transition states and free-energy landscapes from end-point structures alone.

    Why it matters: It removes the need for predefined collective variables in simulating rare molecular transitions at tractable cost.

Sep 15Tue
  1. medrxiv.org49

    Beyond tumor volume: connectomic measures of tumor burden provide superior prognostic information across tumor compartments in glioblastoma

    A tractography-derived measure of brain-wide tumor involvement, the lesion–tract density index (L-TDI), outperformed conventional tumor volume for predicting overall survival in 999 patients with newly diagnosed glioblastoma across multiple institutions. Tumor volume's prognostic value depended strongly on analytical design and was largely confined to the contrast-enhancing compartment, whereas L-TDI showed robust associations with overall survival across thresholds and tumor compartments and retained its value after adjustment for established clinical variables. The findings support assessing glioblastoma prognosis as a brain-wide disease rather than by local tumor extent.

    Why it matters: It shows a connectomic tumor-burden measure beats conventional volume for glioblastoma survival prediction in 999 patients.

  2. medrxiv.org43

    Cross-Source Progression Assessment in Advanced Pancreatic Cancer: An Opportunity-Adjusted Six-State Analysis

    Cross-source progression assessment in advanced pancreatic cancer frequently failed to yield immediate confirmation of progression. Among 645 patients in the primary estimand, only 25 (3.88%) showed same-day concordance, 219 (33.95%) confirmation, 108 (16.74%) explicit nonprogression, and 166 (25.74%) were indeterminate. Among classifiable first opportunities, 33.03% documented explicit nonprogression, supporting an opportunity-adjusted six-state framework over binary discordance estimates.

    Why it matters: Quantifies how often oncology and radiology sources disagree on progression, affecting how progression endpoints are interpreted.

Sep 14Mon
  1. Nature54

    Predicting genome-wide functional constraints with GPN-Star.

    GPN-Star, a phylogeny-aware genomic language model that uses whole-genome alignments and species trees, outperforms previous methods across variant effect prediction tasks in coding and non-coding human genome regions. Trained on vertebrate, mammal and primate alignments, it improves prioritization of pathogenic and fine-mapped GWAS variants, yields strong complex trait heritability enrichments, and improves rare variant association testing power. Versions trained for five model organisms, from mouse to Arabidopsis, show the framework generalizes.

    Why it matters: A phylogeny-aware language model that beats prior methods on variant effect prediction and human genetics applications across species.

  2. Sci Adv47

    Amplification of RNA for identification of Zika and HCV in whole blood.

    A blood drying protocol with thermal treatments and primer-limited reverse transcription stabilizes RNA in whole blood, allowing direct amplification without extraction, purification, or cold-chain logistics. Detection reached 10 copies per microliter for Zika virus and 1 international unit per microliter for HCV, and larger blood volumes achieved single-copy sensitivity without sample loss. Zika and HCV were detected with a portable fluorometer, supporting field-deployable point-of-care diagnostics.

    Why it matters: It removes extraction and cold-chain requirements from whole-blood RNA testing, enabling point-of-care Zika and HCV diagnosis.

  3. medrxiv.org45

    Matched marrow and blood profiling reveals compartment- and feature-specific liquid-biopsy signals in multiple myeloma

    Peripheral-blood cfDNA matched or exceeded marrow-plasma cfDNA as a liquid biopsy for multiple myeloma, despite the tumor's marrow confinement. In 74 patients profiled across 372 cfDNA time points, blood cfDNA recovered marrow-defined CNAs and mutations at 77.4% vs 72.0% and 69.2% vs 65.4%, and at high tumor fraction adverse-lesion sensitivity reached 100% in both compartments. Marrow cfDNA did show distinct, handling-sensitive fragmentomic architecture (LOOCV AUC=0.910), so compartment, biomarker class, tumor fraction and processing all shape liquid-biopsy performance.

    Why it matters: It shows a simpler blood draw is not inferior to marrow-derived cfDNA for myeloma genomic profiling, with practical processing caveats.

  4. medrxiv.org40

    Dosimetric Impact of Residual Intrafraction Motion in Gated MR-Guided Prostate SBRT With Focal Dose Intensification

    Residual intrafraction motion during gated MR-guided prostate SBRT with simultaneous integrated boost caused directionally asymmetric coverage loss, hitting the boosted GTV hardest: per-fraction median GTV deviations were −1.2% for D95 and −5.6% for V45Gy across 150 fractions in 30 patients. Motion-inclusive dose reconstruction yielded asymmetric internal target volume margins (2/2/1/2/1/2 mm for GTV) that achieved sufficient coverage in about 94% of fractions per direction, at the cost of an average 6.9 ± 4.7% reduction in gating duty cycle.

    Why it matters: Provides concrete population-based margins that trade a small loss of delivery efficiency for robust GTV coverage in gated MR-guided prostate SBRT.

Sep 12Sat
  1. medrxiv.org58

    Effective tumor kinetics inferred from single routine H&E biopsies enable counterfactual virtual radiotherapy trials

    Patient-specific proliferation and diffusion rates of a reaction-diffusion model can be inferred from a single routine H&E biopsy by fitting cell-nucleus point patterns, validated across eleven multicenter cohorts. The derived dispersion length and front velocity stratified progression-free and overall survival independent of routine covariates. A virtual glioblastoma trial allocating hypofractionation to faster-growing tumors and dose intensification to slower-growing ones added 96.7 days of restricted mean progression-free survival over standard of care (permutation p < 0.001).

    Why it matters: It turns a single routine H&E biopsy into patient-specific tumor growth parameters usable for survival prediction and virtual treatment trials.

Sep 11Fri
  1. Nat Biotechnol53

    Programmable promoter editing for precise control of transgene expression.

    DIAL is a modular framework for building editable promoters that tune transgene expression in fine, heritable steps. Recombinase-mediated excision of nested spacers between zinc finger transcription factor binding sites and the core promoter generates a tunable range of unimodal expression setpoints from a single promoter, with small-molecule temporal control. Lentiviral delivery produced multiple setpoints in primary cells and induced pluripotent stem cells, and enabled mapping of transgene levels to phenotype in direct conversion to induced motor neurons.

    Why it matters: Gives a general method for titrating and locking in transgene expression levels, useful wherever gene dosage matters.

  2. Nat Biotechnol56

    Engineered genomic attachment sites for site-specific recombinases enable high-efficiency integration in plants and human cells.

    Rationally engineered chimeric attachment sites boost Bxb1-mediated integration efficiency in human cells and plants. The attB(V111) variant achieved 51.9% integration in HEK293T cells (1.7-fold over wild-type attB) and 35.6% in rice protoplasts (4.4-fold), and paired with a Bxb1 catalytic-domain mutant delivered 31% integration of a CD19 CAR cassette and 25% of an ornithine transcarbamylase cassette in human cells. In rice, a 5.8 kb herbicide-resistance cassette integrated in 24% of regenerated plants, with heritable transmission to T1 plants.

    Why it matters: Engineered attachment sites substantially raise recombinase-mediated integration efficiency across plants and human cells.

Sep 10Thu
  1. Sci Adv58

    Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain.

    Sea nettle jellyfish venom kills human cells through apoptosis and necroptosis, and whole-genome CRISPR screening identifies proteoglycan biosynthesis as the key host pathway governing venom action. Heparin blocks venom cytotoxicity at a clinically relevant dose, works therapeutically even 1 hour after exposure, and in vivo reduces venom-induced acute spontaneous pain, thermal hyperalgesia, and mechanical allodynia. The findings point to repurposing heparin as a prophylactic or therapeutic against sea nettle stings, for which no rational treatments exist.

    Why it matters: It identifies a host pathway for sea nettle venom action and repurposes heparin as a treatment for stings affecting millions yearly.

  2. Nature62

    Proximity-guided graph learning reveals tumour-associated proximity antigens.

    An industrialized surface protein proximity-mapping workflow produced 248 proximity maps across 12 receptor tyrosine kinases and 28 tumour cell systems, yielding MetaMap, a framework that defines spatial protein communities and the concept of tumour-associated proximity antigens (TAPAs). Applied within a multimodal prioritization framework, it identified EGFR-CDCP1 as a TAA-TAPA pair that enhances tumour cell killing across therapeutic modalities, making disease-specific membrane proximity a design principle for precision multispecific therapeutics.

    Why it matters: It turns membrane spatial proximity, not expression alone, into a criterion for selecting co-targets for multispecific therapeutics.

  3. Nature49

    Synthesis of pyrroles from isoxazoles by an O-to-C skeletal edit.

    Pyrroles can now be made directly from isoxazoles by an O-to-C skeletal edit that swaps the single differing ring atom in a one-pot sequence. The key intermediate is an N-propargylic enaminone, giving a retrosynthetic disconnection orthogonal to traditional pyrrole syntheses. A predictive computational model captures the conformational features controlling the reaction outcome, enabling regioselective access to otherwise elusive pyrrole scaffolds.

    Why it matters: It converts isoxazoles to pyrroles with a single-atom ring edit, opening new routes to medicinally relevant scaffolds.

Sep 9Wed
  1. Nat Biotechnol63

    Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.

    Light-sheet live imaging of late-stage preimplantation human embryos, enabled by mRNA electroporation of nuclear DNA labels, shows chromosome segregation errors arising de novo immediately before implantation, including multipolar spindles, lagging chromosomes, misalignment and mitotic slippage. Most lagging chromosomes are passively inherited rather than reincorporated, and most labeled cells remain externally positioned, consistent with placental fate. The findings question clinical uses of preimplantation genetic testing for aneuploidy.

    Why it matters: Direct imaging shows aneuploidy can arise after fertilization at late preimplantation stages, questioning PGT-A interpretation.

Sep 8Tue
  1. Nature57

    CRISPR-Cas regulates expression of embedded anti-phage defence systems.

    Type I CRISPR-Cas loci embed and transcriptionally control diverse innate defence systems, a regulatory paradigm named CRISIS. Small non-canonical crRNA-like RNAs guide the I-C Cascade effector to promoters of immune cassettes, keeping basal expression sufficient for antiviral activity while preventing fitness costs such as growth impairment and exclusion of beneficial plasmids. When CRISPR-Cas is compromised by mutation or anti-CRISPR proteins, transcription of the embedded defences surges, raising innate immunity at the expense of host fitness. This casts CRISPR-Cas as a supervisor of a layered prokaryotic defence network, an 'immunity guard' strategy.

    Why it matters: It recasts CRISPR-Cas as a transcriptional regulator of other defence systems, not just an adaptive immune nuclease.

  2. Sci Adv45

    Three-dimensional reconfigurable magnetic microswarms with boundary-transcending capabilities.

    Synchronizing a global rotating magnetic field with a co-rotating local gradient generates enhanced rotating fields that drive 3D movement of magnetic microparticles across solid-liquid and liquid-air boundaries. The resulting tornado-like microswarms reversibly switch between 2D and 3D patterns and between single and dual collectives, trap and transport cargo via convection flows, and carried levamisole vertically across intermediate barriers to induce localized arrhythmic beating of cardiomyocytes. The work points to uses in biological mechanism discovery and drug screening.

  3. Science55

    In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.

    In situ cryo-electron tomography of human multiciliated epithelial cells resolved the ciliary transition zone at subnanometer resolution and identified nine constituent proteins, including ECT2L and DZANK1, which form the major linker complexes between adjacent doublet microtubules. Biallelic loss-of-function variants in either gene cause primary ciliary dyskinesia, disrupting TZ architecture and impairing mucociliary clearance. The work establishes a direct genetic link between transition zone defects and human motile ciliopathy.

    Why it matters: It links specific transition zone linker proteins to primary ciliary dyskinesia at subnanometer resolution.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org